Effect of Bronchipret on Antiviral Immune Response in Patients With Mild COVID-19 (BroVID)

Effect of Bronchipret on Antiviral Immune Response in Patients With Mild COVID-19 (BroVID)

There is currently an urgent need for effective and safe treatments of Coronavirus Disease (COVID) - 19 and the cytokine storm that is responsible for the development of patient's Acute Respiratory Distress Syndrome (ARDS).

As Bronchipret has been proven to be a very safe medicine, it is not expected that it would lead to the development of severe adverse effects in COVID-19 patients. Bronchipret can therefore be recommended as effective and safe supplementary treatments of COVID-19, even more so considering the positive effects shown in vitro. Thus, this randomized study is conducted to assess the effect of Bronchipret on the immune response and recovery in patients with mild COVID-19 by assessing several blood parameters as well as the symptom recovery and improvement in comparison to patients who do not receive Bronchipret. Another aim of this feasibility study is to determine the best possible primary endpoint, i.e. which shows the greatest effect according to Cohen.

Study Overview

• Status: Recruiting
• Conditions: COVID-19
• Intervention / Treatment: Drug: Bronchipret

Detailed Description

Although intensive research efforts have been underway worldwide, so far, only few effective treatment against the disease has been brought to the market in Germany. Based on the pathological features and different clinical phases of COVID-19, particularly in patients with moderate to severe COVID- 19, the classes of drugs used are antiviral agents (e.g., remdesivir), inflammation inhibitors/antirheumatic drugs (e.g., dexamethasone), low molecular weight heparins, plasma, and hyperimmune immunoglobulins Bronchipret exhibits multidirectional anti-inflammatory effects as demonstrated in vitro and in vivo studies. Several clinical trials have demonstrated positive effects of Bronchipret, a fixed combination of thyme herb and ivy leaf fluid extracts, on symptom relieve and recovery time in patients with acute bronchitis and cough. There is currently an urgent need for effective and safe treatments of COVID- 19 and the cytokine storm that is responsible for the development of Acute Respiratory Distress Syndrome (ARDS).

As Bronchipret has been proven to be a very safe medicine, it is not expected that it would lead to the development of severe adverse effects in COVID-19 patients. Bronchipret can therefore be recommended as effective and safe supplementary treatments of COVID-19, even more so considering the positive effects shown in vitro. Thus, this randomized study will be conducted to assess the effect of Bronchipret on the immune response and recovery in patients with mild COVID-19 by assessing several blood parameters as well as the symptom recovery and improvement in comparison to patients who do not receive Bronchipret. Another aim of this feasibility study is to determine the best possible primary endpoint, i.e. which shows the greatest effect according to Cohen.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Christin Jonetzko; Phone Number: 004969630180210; Email: christin.jonetzko@itmp.fraunhofer.de
• Study Contact Backup: Name: Anja Kuehne; Email: anja.kuehne@itmp.fraunhofer.de

Study Locations

• Germany
  • Hessia
    • Frankfurt, Hessia, Germany, 60596
      • Recruiting
      • Fraunhofer ITMP - early clinical development
      • Contact: Stephan Schaefer, MD; Email: stephan.schaefer@itmp.fraunhofer.de
      • Contact: Ulf Henkemeier, MSc; Email: ulf.henkemeier@itmp.fraunhofer.de
      • Principal Investigator: Stephan Schaefer, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients ≥ 18 years and ≤ 75 years

   o If > 50 years, complete COVID-19 vaccination mandatory

2. SARS-CoV-2 infection confirmed by PCR test ≤ 4 days before screening/baseline visit
3. Onset of the earliest symptoms < 7 days before screening/baseline visit

4. Mild COVID-19 with the following symptoms (outpatient management/non hospitalized patients):

   ᴑ Cough and ᴑ At least one other symptom (e.g., sore throat, nasal congestion, headache, nausea, low energy/fatigue, muscle or body ache, shortness of breath, fever, diarrhea, altered sense of smell or taste)

5. Written informed consent obtained prior to the initiation of any protocol-required procedures by the patient
6. Willingness to comply to study procedures and study protocol

Exclusion Criteria:

1. WHO score ≥ 3
2. Other advanced or chronic lung diseases (Chronic obstructive pulmonary disease (COPD), silicosis, bronchial asthma)
3. Unable to take oral medication
4. Body mass index (BMI) > 35 or ≤ 43kg
5. Requirement for oxygen administration
6. Current hospitalization
7. Known hypersensitivity to the active substances ivy, thyme, plants of the aralia family or other labiates (Lamiaceae), birch, mugwort, celery or to any of the excipients
8. Patients with rare hereditary fructose intolerance
9. Inability to monitor body temperature
10. Patients regularly taking immune suppressive medication, nonsteroidal anti-rheumatic drug(s) (NSARs) or steroids (e.g., because of underlying disease)
11. Known significant concomitant diseases or serious and/or uncontrolled diseases that are likely to interfere with the evaluation of the patient's safety and with the study outcome such as stem cell or organ transplantation within the last 5 years, cardiovascular disease, diabetes mellitus, chronic liver disease, chronic kidney disease including dialysis patients, sickle cell anemia or thalassemia, and other forms of immunosuppression (e.g. tumor patients, HIV-infected patients with weakened immune system, iatrogenic immunosuppression) as judged by the study physician according to patient's reports.
12. COVID-19 vaccination planned within study period and/or COVID-19 vaccination within the last 28 days
13. Women pregnant (patient reported at pre-Screening and confirmation via pregnancy test at Screening/baseline) or nursing
14. Males or females of reproductive potential not willing to use effective contraception (defined as PEARL index <1 - e.g. contraceptive pills/intra-uterine devices (IUD))
15. Alcohol, drug or chemical abuse
16. Current participation in another interventional clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Bronchipret; Bronchipret syrup (3x 5,4 ml daily, according to summary of product characteristics) until day 14	Drug: Bronchipret; Bronchipret syrup (3x 5,4 ml daily) until day 14
NO_INTERVENTION: standard of care; no study intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in average concentration of immunologic markers	concentration of Interleukin 2 (IL-2)	Comparison Baseline to day 7
Change in average concentration of immunologic markers - IL4	concentration of Interleukin (IL) 4	Comparison Baseline to day 7
Change in average concentration of immunologic markers - Interleukin (IL)-6	concentration of IL-6	Comparison Baseline to day 7
Change in average concentration of immunologic markers - IL-8	concentration of IL-8	Comparison Baseline to day 7
Change in average concentration of immunologic markers - IL-10	concentration of IL-10	Comparison Baseline to day 7
Change in average concentration of immunologic markers - Interferon y	concentration of interferon (INF) y	Comparison Baseline to day 7
Change in average concentration of immunologic markers- c-reactive protein (CRP)	concentration of c-reactive protein (CRP)	Comparison Baseline to day 7
Change in average concentration of immunologic markers - IL-1β	concentration of IL-1β	Comparison Baseline to day 7
Change in average concentration of immunologic markers - Interferon (INF) α	concentration of INFα	Comparison Baseline to day 7
Change in average concentration of immunologic markers - TNFα	concentration of tumor necrosis factor alpha (TNFα)	Comparison Baseline to day 7
Change in average number of immunologic markers - neutrophils	number of neutrophils	Comparison Baseline to day 7
Change in average number of immunologic markers - lymphocytes	number of lymphocytes	Comparison Baseline to day 7
Change in average number of immunologic markers - monocytes	number of monocytes	Comparison Baseline to day 7
Change in average number of immunologic markers - eosinophils	number of eosinophils	Comparison Baseline to day 7
Change in average number of immunologic markers - basophils	number of basophils	Comparison Baseline to day 7
Change in average number of immunologic markers - platelets	number of platelets	Comparison Baseline to day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of blood parameters and change to BL - IL2	percentage of change of concentration of IL-2	Day 4
Concentration of blood parameters and change to BL	absolute change of concentration of IL-2	Day 4
Concentration of blood parameters and change to BL (percentage): IL2	percentage of change of concentration of IL-2	Day 7
Concentration of blood parameters and change to BL (absolute change): IL2	absolute change of concentration of IL-2	Day 7
Concentration of blood parameters and change to BL (absolute change): IL2	absolute change of concentration of IL-2	Day 14
Concentration of blood parameters and change to BL (percentage): IL2	percentage of change of concentration of IL-2	Day 14
Concentration of blood parameters and change to BL (percentage) IL4	percentage of change of concentration of IL-4	Day 4
Concentration of blood parameters and change to BL (absolute change): IL4	absolute change of concentration of IL-4	Day 7
Concentration of blood parameters and change to BL (percentage) IL4	percentage of change of concentration of IL-4	Day 7
Concentration of blood parameters and change to BL (absolute change) IL4	absolute change of concentration of IL-4	Day 14
Concentration of blood parameters and change to BL (percentage) IL4	percentage of change of concentration of IL-4	Day 14
Concentration of blood parameters and change to BL (absolute change) IL6	absolute change of concentration of IL-6	Day 4
Concentration of blood parameters and change to BL (percentage) IL6	percentage of change of concentration of IL-6	Day 4
Concentration of blood parameters and change to BL (absolute change) IL6	absolute change of concentration of IL-6	Day 7
Concentration of blood parameters and change to BL (percentage) IL6	percentage of change of concentration of IL-6	Day 7
Concentration of blood parameters and change to BL (percentage) IL6	percentage of change of concentration of IL-6	Day 14
Concentration of blood parameters and change to BL (absolute change) IL6	absolute change of concentration of IL-6	Day 14
Concentration of blood parameters and change to BL (percentage) IL8	percentage of change of concentration of IL-8	Day 4
Concentration of blood parameters and change to BL (absolute change) IL8	absolute change of concentration of IL-8	Day 4
Concentration of blood parameters and change to BL (percentage):	percentage of change of concentration of IL-8	Day 7
Concentration of blood parameters and change to BL (absolute change):	absolute change of concentration of IL-8	Day 7
Concentration of blood parameters and change to BL (percentage):	percentage of change of concentration of IL-8	Day 14
Concentration of blood parameters and change to BL (absolute change IL8):	absolute change of concentration of IL-8	Day 14
Concentration of blood parameters and change to BL (absolute change IL10):	absolute change of concentration of IL-10	Day 4
Concentration of blood parameters and change to BL (IL10 percentage):	percentage of change of concentration of IL-10	Day 4
Concentration of blood parameters and change to BL (absolute change IL10):	absolute change of concentration of IL-10	Day 7
Concentration of blood parameters and change to BL (percentage): IL10	percentage of change of concentration of IL-10	Day 7
Concentration of blood parameters and change to BL (absolute change IL10):	absolute change of concentration of IL-10	Day 14
Concentration of blood parameters and change to BL (percentage): IL10	percentage of change of concentration of IL-10	Day 14
Concentration of blood parameters and change to BL (INFy percentage):	percentage of change of concentration of INFy	Day 4
Concentration of blood parameters and change to BL (absolute change INFy):	absolute change of concentration of INFy	Day 4
Concentration of blood parameters and change to BL (percentage): INFy	percentage of change of concentration of INFy	Day 7
Concentration of blood parameters and change to BL (absolute change): INFy	absolute change of concentration of INFy	Day 7
Concentration of blood parameters and change to BL (percentage): INFy	percentage of change of concentration of INFy	Day 14
Concentration of blood parameters and change to BL (absolute change): INFy	absolute change of concentration of INFy	Day 14
Concentration of blood parameters and change to BL (absolute change): CRP	absolute change of concentration of CRP	Day 4
Concentration of blood parameters and change to BL (percentage): CRP	percentage of change of concentration of CRP	Day 4
Concentration of blood parameters and change to BL (absolute change): CRP	absolute change of concentration of CRP	Day 7
Concentration of blood parameters and change to BL (percentage): CRP	percentage of change of concentration of CRP	Day 7
Concentration of blood parameters and change to BL (absolute change): CRP	absolute change of concentration of CRP	Day 14
Concentration of blood parameters and change to BL (percentage): CRP	percentage of change of concentration of CRP	Day 14
Concentration of blood parameters and change to BL (percentage): IL-1β	percentage of change of concentration of IL-1β	Day 4
Concentration of blood parameters and change to BL (absolute change): IL-1β	absolute change of concentration of IL-1β	Day 4
Concentration of blood parameters and change to BL (percentage): IL-1β	percentage of change of concentration of IL-1β	Day 7
Concentration of blood parameters and change to BL (absolute change): IL-1β	absolute change of concentration of IL-1β	Day 7
Concentration of blood parameters and change to BL (percentage): IL-1β	percentage of change of concentration of IL-1β	Day 14
Concentration of blood parameters and change to BL (absolute change): IL-1β	absolute change of concentration of IL-1β	Day 14
Concentration of blood parameters and change to BL (absolute change): INFα	absolute change of concentration of INFα	Day 4
Concentration of blood parameters and change to BL (percentage): INFα	percentage of change of concentration of INFα	Day 4
Concentration of blood parameters and change to BL (absolute change):INFα	absolute change of concentration of INFα	Day 7
Concentration of blood parameters and change to BL (percentage): INFα	percentage of change of concentration of INFα	Day 7
Concentration of blood parameters and change to BL (percentage): INFα	percentage of change of concentration of INFα	Day 14
Concentration of blood parameters and change to BL (absolute change): INFα	absolute change of concentration of INFα	Day 14
Concentration of blood parameters and change to BL (absolute change): TNFα,	absolute change of concentration of TNFα,	Day 4
Concentration of blood parameters and change to BL (percentage): TNFα,	percentage of change of concentration of TNFα,	Day 4
Concentration of blood parameters and change to BL (absolute change): TNFα,	absolute change of concentration of TNFα,	Day 7
Concentration of blood parameters and change to BL (percentage): TNFα,	percentage of concentration of TNFα,	Day 7
Concentration of blood parameters and change to BL (absolute change): TNFα,	absolute change of concentration of TNFα,	Day 14
Concentration of blood parameters and change to BL (percentage): TNFα,	percentage of change of concentration of TNFα,	Day 14
Concentration of blood parameters and change to BL (percentage): neutrophils	percentage change of neutrophils	Day 4
Concentration of blood parameters and change to BL (absolute change): neutrophils	absolute change of neutrophils number	Day 4
Concentration of blood parameters and change to BL (percentage): neutrophils	percentage change of neutrophils	Day 7
Concentration of blood parameters and change to BL (absolute change): neutrophils	absolute change of neutrophils number	Day 7
Concentration of blood parameters and change to BL (percentage): neutrophils	percentage change of neutrophils	Day 14
Concentration of blood parameters and change to BL (absolute change): neutrophils	absolute change of neutrophils number	Day 14
Concentration of blood parameters and change to BL (absolute change): lymphocytes	absolute change of lymphocytes number	Day 4
Concentration of blood parameters and change to BL (percentage): lymphocytes	percentage change of lymphocytes	Day 4
Concentration of blood parameters and change to BL (absolute change): lymphocytes	absolute change of lymphocytes number	Day 7
Concentration of blood parameters and change to BL (percentage): lymphocytes	percentage change of lymphocytes	Day 7
Concentration of blood parameters and change to BL (absolute change): lymphocytes	absolute change of lymphocytes number	Day 14
Concentration of blood parameters and change to BL (percentage): lymphocytes	percentage change of lymphocytes	Day 14
Concentration of blood parameters and change to BL (percentage): monocytes	percentage change of monocytes	Day 4
Concentration of blood parameters and change to BL (absolute change): monocytes	absolute change of monocytes number	Day 4
Concentration of blood parameters and change to BL (percentage): monocytes	percentage change of monocytes	Day 7
Concentration of blood parameters and change to BL (absolute change): monocytes	absolute change of monocytes number	Day 7
Concentration of blood parameters and change to BL (percentage): monocytes	percentage of change of monocytes	Day 14
Concentration of blood parameters and change to BL (absolute change): monocytes	absolute change of monocytes number	Day 14
Concentration of blood parameters and change to BL (absolute change): eosinophils	absolute change of eosinophils number	Day 4
Concentration of blood parameters and change to BL (percentage): eosinophils	percentage of change of eosinophils	Day 4
Concentration of blood parameters and change to BL (percentage): eosinophils	percentage of change of eosinophils	Day 7
Concentration of blood parameters and change to BL (absolute change): eosinophils	absolute change of eosinophils number	Day 7
Concentration of blood parameters and change to BL (percentage): eosinophils	percentage of change of eosinophils	Day 14
Concentration of blood parameters and change to BL (absolute change): eosinophils	absolute change of eosinophils number	Day 14
Concentration of blood parameters and change to BL (percentage):	percentage of change of basophils number	Day 4
Concentration of blood parameters and change to BL (absolute change):	absolute change of basophils number	Day 4
Concentration of blood parameters and change to BL (absolute change):	absolute change of basophils number	Day 7
Concentration of blood parameters and change to BL (percentage):	percentage of change of basophils	Day 7
Concentration of blood parameters and change to BL (absolute change):	absolute change of basophils number	Day 14
Concentration of blood parameters and change to BL (percentage):	percentage of change of basophils	Day 14
Concentration of blood parameters and change to BL (percentage):	percentage of change of platelets	Day 4
Concentration of blood parameters and change to BL (absolute change):	absolute change of platelet number	Day 4
Concentration of blood parameters and change to BL (percentage):	percentage of change of platelets	Day 7
Concentration of blood parameters and change to BL (absolute change):	absolute change of platelet number	Day 7
Concentration of blood parameters and change to BL (percentage):	percentage of change of platelets	Day 14
Concentration of blood parameters and change to BL (absolute change):	absolute change of platelet number	Day 14
Concentration of blood parameters and change to BL (percentage):	percentage of change of lactate dehydrogenase (LDH)	Day 4
Concentration of blood parameters and change to BL (absolute change):	absolute change of lactate dehydrogenase (LDH)	Day 4
Concentration of blood parameters and change to BL (absolute change):	absolute change of LDH	Day 7
Concentration of blood parameters and change to BL (percentage):	percentage of change of LDH	Day 7
Concentration of blood parameters and change to BL (absolute change):	absolute change of LDH	Day 14
Concentration of blood parameters and change to BL (percentage):	percentage of change of LDH	Day 14
Concentration of blood parameters and change to BL (percentage):	percentage of change of ferritin	Day 4
Concentration of blood parameters and change to BL (absolute change):	absolute change of ferritin	Day 4
Concentration of blood parameters and change to BL (percentage):	percentage of change of ferritin	Day 7
Concentration of blood parameters and change to BL (absolute change):	absolute change of ferritin	Day 7
Concentration of blood parameters and change to BL (percentage):	percentage of change of ferritin	Day 14
Concentration of blood parameters and change to BL (absolute change):	absolute change of ferritin	Day 14
Concentration of blood parameters and change to BL (absolute change):	absolute change of haemoglobin	Day 4
Concentration of blood parameters and change to BL (percentage):	percentage of change of haemoglobin	Day 4
Concentration of blood parameters and change to BL (absolute change):	absolute change of haemoglobin	Day 7
Concentration of blood parameters and change to BL (percentage):	percentage of change of haemoglobin	Day 7
Concentration of blood parameters and change to BL (absolute change):	absolute change of haemoglobin	Day 14
Concentration of blood parameters and change to BL (percentage):	percentage of change of haemoglobin	Day 14
Concentration of blood parameters and change to BL (absolute change):	absolute change of alanine aminotransferase (ALT)	Day 4
Concentration of blood parameters and change to BL (percentage):	percentage of change of alanine aminotransferase (ALT)	Day 4
Concentration of blood parameters and change to BL (absolute change):	absolute change of alanine aminotransferase (ALT)	Day 7
Concentration of blood parameters and change to BL (percentage):	percentage of change of alanine aminotransferase (ALT)	Day 7
Concentration of blood parameters and change to BL (percentage):	percentage of change of alanine aminotransferase (ALT)	Day 14
Concentration of blood parameters and change to BL (absolute change):	absolute change of alanine aminotransferase (ALT)	Day 14
Concentration of blood parameters and change to BL (absolute change):	absolute change of Aspartate aminotransferase (AST)	Day 4
Concentration of blood parameters and change to BL (absolute change):	absolute change of Aspartate aminotransferase (AST)	Day 7
Concentration of blood parameters and change to BL (percentage):	percentage of change of Aspartate aminotransferase (AST)	Day 7
Concentration of blood parameters and change to BL (absolute change):	absolute change of Aspartate aminotransferase (AST)	Day 14
Concentration of blood parameters and change to BL (percentage):	percentage of change of Aspartate aminotransferase (AST)	Day 14
Concentration of blood parameters and change to BL (percentage):	percentage of change of activated partial thromboplastin time	Day 4
Concentration of blood parameters and change to BL (absolute change):	absolute change of activated partial thromboplastin time	Day 4
Concentration of blood parameters and change to BL (absolute change):	absolute change of activated partial thromboplastin time	Day 7
Concentration of blood parameters and change to BL (percentage):	percentage of change of activated partial thromboplastin time	Day 7
Concentration of blood parameters and change to BL (percentage):	percentage of change of activated partial thromboplastin time	Day 14
Concentration of blood parameters and change to BL (absolute change):	absolute change of activated partial thromboplastin time	Day 14
Concentration of blood parameters and change to BL (absolute change):	absolute change of prothrombin Z	Day 4
Concentration of blood parameters and change to BL (percentage):	percentage of change of prothrombin Z	Day 4
Concentration of blood parameters and change to BL (absolute change):	absolute change of prothrombin Z	Day 7
Concentration of blood parameters and change to BL (percentage):	percentage of change of prothrombin Z	Day 7
Concentration of blood parameters and change to BL (absolute change):	absolute change of prothrombin Z	Day 14
Concentration of blood parameters and change to BL (percentage):	percentage of change of prothrombin Z	Day 14
Concentration of blood parameters and change to BL (percentage):	percentage of change of fibrinogen	Day 4
Concentration of blood parameters and change to BL (absolute change):	absolute change of fibrinogen	Day 4
Concentration of blood parameters and change to BL (percentage):	percentage of change of fibrinogen	Day 7
Concentration of blood parameters and change to BL (absolute change):	absolute change of fibrinogen	Day 7
Concentration of blood parameters and change to BL (percentage):	percentage of change of fibrinogen	Day 14
Concentration of blood parameters and change to BL (absolute change):	absolute change of fibrinogen	Day 14
Concentration of blood parameters and change to BL (absolute change):	absolute change of d-dimeric	Day 4
Concentration of blood parameters and change to BL (percentage):	percentage of change of d-dimeric	Day 4
Concentration of blood parameters and change to BL (absolute change):	absolute change of d-dimeric	Day 7
Concentration of blood parameters and change to BL (percentage):	percentage of change of d-dimeric	Day 7
Concentration of blood parameters and change to BL (absolute change):	absolute change of d-dimeric	Day 14
Concentration of blood parameters and change to BL (percentage):	percentage of change of d-dimeric	Day 14
Concentration of blood parameters and change to BL (percentage):	percentage of change of fibrin-degranulation products	Day 4
Concentration of blood parameters and change to BL (absolute change):	absolute change of fibrin-degranulation products	Day 4
Concentration of blood parameters and change to BL (percentage):	percentage of change of fibrin-degranulation products	Day 7
Concentration of blood parameters and change to BL (absolute change):	absolute change of fibrin-degranulation products	Day 7
Concentration of blood parameters and change to BL (percentage):	percentage of change of fibrin-degranulation products	Day 14
Concentration of blood parameters and change to BL (absolute change):	absolute change of fibrin-degranulation products	Day 14
Concentration of blood parameters and change to BL (absolute change):	absolute change of anti-thrombin III activity	Day 4
Concentration of blood parameters and change to BL (percentage):	percentage of change of anti-thrombin III activity	Day 4
Concentration of blood parameters and change to BL (absolute change):	absolute change of anti-thrombin III activity	Day 7
Concentration of blood parameters and change to BL (percentage):	percentage of change of anti-thrombin III activity	Day 7
Concentration of blood parameters and change to BL (absolute change):	absolute change of anti-thrombin III activity	Day 14
Concentration of blood parameters and change to BL (percentage):	percentage of change of anti-thrombin III activity	Day 14
Concentration of blood parameters and change to BL (percentage):	percentage of change of Immunglobulin M (IgM)	Day 4
Concentration of blood parameters and change to BL (absolute change):	absolute change of Immunglobulin M (IgM)	Day 4
Concentration of blood parameters and change to BL (percentage):	percentage of change of Immunglobulin M (IgM)	Day 7
Concentration of blood parameters and change to BL (absolute change):	absolute change of Immunglobulin M (IgM)	Day 7
Concentration of blood parameters and change to BL (percentage):	percentage of change of Immunglobulin M (IgM)	Day 14
Concentration of blood parameters and change to BL (absolute change):	absolute change of Immunglobulin M (IgM)	Day 14
Concentration of blood parameters and change to BL (absolute change):	absolute change of Immunglobulin G (IgG)	Day 4
Concentration of blood parameters and change to BL (percentage):	percentage of change of Immunglobulin G (IgG)	Day 4
Concentration of blood parameters and change to BL (absolute change):	absolute change of Immunglobulin G (IgG)	Day 7
Concentration of blood parameters and change to BL (percentage):	percentage of change of Immunglobulin G (IgG)	Day 7
Concentration of blood parameters and change to BL (absolute change):	absolute change of Immunglobulin G (IgG)	Day 14
Concentration of blood parameters and change to BL (percentage):	percentage of change of Immunglobulin G (IgG)	Day 14
Concentration of blood parameters and change to BL (percentage):	percentage of change of Creatinin	Day 4
Concentration of blood parameters and change to BL (absolute change):	absolute change of Creatinin	Day 4
Concentration of blood parameters and change to BL (percentage):	percentage of change of Creatinin	Day 7
Concentration of blood parameters and change to BL (absolute change):	absolute change of Creatinin	Day 7
Concentration of blood parameters and change to BL (percentage):	percentage of change of Creatinin	Day 14
Concentration of blood parameters and change to BL (absolute change):	absolute change of Creatinin	Day 14
Neutrophil to lymphocyte ratio	Neutrophil to lymphocyte number ratio	Day 4
Neutrophil to lymphocyte ratio	Neutrophil to lymphocyte number ratio	Day 7
Neutrophil to lymphocyte ratio	Neutrophil to lymphocyte number ratio	Day 14
IL-6/IL-10 ratio	IL-6/IL-10 concentration ratio	Day 4
IL-6/IL-10 ratio	IL-6/IL-10 concentration ratio	Day 7
IL-6/IL-10 ratio	IL-6/IL-10 concentration ratio	Day 14
IL-6/INFy ratio	IL-6/INFy concentration ratio	Day 14
IL-6/INFy ratio	IL-6/INFy concentration ratio	Day 7
IL-6/INFy ratio	IL-6/INFy concentration ratio	Day 4
Assessment of symptom improvement/worsening	FDA (Federal drug agency) recommended symptom questionnaire - higher scores describe worse symptoms, scoring 0 to 3 (question 1 to 12) and 0 to 2 (question 13 and 14)	Day 4
Assessment of symptom improvement/worsening	FDA (Federal drug agency) recommended symptom questionnaire - higher scores describe worse symptoms, scoring 0 to 3 (question 1 to 12) and 0 to 2 (question 13 and 14)	Day 7
Assessment of symptom improvement/worsening	FDA (Federal drug agency) recommended symptom questionnaire - higher scores describe worse symptoms, scoring 0 to 3 (question 1 to 12) and 0 to 2 (question 13 and 14)	Day 14
Assessment of symptom improvement/worsening	FDA (Federal drug agency) recommended symptom questionnaire - higher scores describe worse symptoms, scoring 0 to 3 (question 1 to 12) and 0 to 2 (question 13 and 14)	Day 28
Assessment of number of symptoms	FDA (Federal drug agency) recommended symptom questionnaire - higher scores describe worse symptoms, scoring 0 to 3 (question 1 to 12) and 0 to 2 (question 13 and 14)	Day 4
Assessment of number of symptoms	FDA (Federal drug agency) recommended symptom questionnaire - higher scores describe worse symptoms, scoring 0 to 3 (question 1 to 12) and 0 to 2 (question 13 and 14)	Day 7
Assessment of number of symptoms	FDA (Federal drug agency) recommended symptom questionnaire - higher scores describe worse symptoms, scoring 0 to 3 (question 1 to 12) and 0 to 2 (question 13 and 14)	Day 14
Assessment of number of symptoms	FDA (Federal drug agency) recommended symptom questionnaire - higher scores describe worse symptoms, scoring 0 to 3 (question 1 to 12) and 0 to 2 (question 13 and 14)	Day 28
Assessment of symptom distribution	FDA (Federal drug agency) recommended symptom questionnaire - higher scores describe worse symptoms, scoring 0 to 3 (question 1 to 12) and 0 to 2 (question 13 and 14)	Day 4
Assessment of symptom distribution	FDA (Federal drug agency) recommended symptom questionnaire - higher scores describe worse symptoms, scoring 0 to 3 (question 1 to 12) and 0 to 2 (question 13 and 14)	Day 7
Assessment of symptom distribution	FDA (Federal drug agency) recommended symptom questionnaire - higher scores describe worse symptoms, scoring 0 to 3 (question 1 to 12) and 0 to 2 (question 13 and 14)	Day 14
Assessment of symptom distribution	FDA (Federal drug agency) recommended symptom questionnaire - higher scores describe worse symptoms, scoring 0 to 3 (question 1 to 12) and 0 to 2 (question 13 and 14)	Day 28
Assessment of defervescence	Time to defervescence in days	Day 28
Assessment of defervescence - number of patients	Number of patients who achieved defervescence	Day 28
Assessment of defervescence - portion of patients	Proportion of patients who achieved defervescence	Day 28
Assessment of defervescence	Absolute temperature values and change to BL	Day 4
Assessment of defervescence	Absolute temperature values and change to BL	Day 7
Assessment of defervescence	Absolute temperature values and change to BL	Day 14
Assessment of defervescence	Absolute temperature values and change to BL	Day 28
Assessment of improvement or absence of coughing	Time to cough reported as mild oder non existent in days	Day 28
Assessment of improvement or absence of coughing	Time to non-existent coughing for all patients in days	Day 28
Assessment of improvement or absence of coughing - proportion of patients	proportion of patients with moderate or severe cough at BL who achieved cough reported as mild or none existent	Day 28
Assessment of improvement or absence of coughing - number of patients	Number of patients with moderate or severe cough at BL who achieved cough reported as mild or none existent	Day 28
Assessment of improvement or absence of coughing	proportion of patients who achieved cough reported as none existent	Day 28
Assessment of intensity and distribution of most bothersome symptom	Intensity of most bothersome symptom assessment done by visual analogue scale (VAS) and change to Baseline - score 0 to 10 cm, higher values describe higher intensity	Day 28
Assessment of intensity and distribution of most bothersome symptom	Most bothersome symptom distribution (i.e.,number and percentage of patients with each symptom) (the most bothersome symptom will be defined by the patient at BL) assessment done by visual analogue scale (VAS) - score 0 to 10 cm, higher values describe higher intensity	Day 28
Proportion of patients who return to usual health	proportion of patients who return to usual health	Day 28
Number of patients who return to usual health	Number of patients who return to usual health	Day 28
proportion of patients who return to usual activity	proportion of patients who return to usual activity	Day 28
Requirement of hospitalisation or oxygen supplementation	Number of patients requiring hospitalisation or oxygen supplementation (patient reported)	Day 28
Requirement of hospitalisation or oxygen supplementation	proportion of patients requiring hospitalisation or oxygen supplementation (patient reported)	Day 28
Disease progression/improvement	Number of patients with improved or progressed disease state (according to world health organisation (WHO) scale) - Score 0 - 10, higher score described more progressed state	Day 4
Disease progression/improvement	proportion of patients with improved or progressed disease state (according to world health organisation (WHO) scale) - Score 0 - 10, higher score described more progressed state	Day 4
Disease progression/improvement	Number of patients with improved or progressed disease state (according to world health organisation (WHO) scale) Score 0 - 10, higher score described more progressed state	Day 7
Disease progression/improvement	proportion of patients with improved or progressed disease state (according to world health organisation (WHO) scale) Score 0 - 10, higher score described more progressed state	Day 7
Disease progression/improvement	Number of patients with improved or progressed disease state (according to world health organisation (WHO) scale) Score 0 - 10, higher score described more progressed state	Day 14
Disease progression/improvement	proportion of patients with improved or progressed disease state (according to world health organisation (WHO) scale), Score 0 - 10, higher score described more progressed state	Day 14
Disease progression/improvement	Number of patients with improved or progressed disease state (according to world health organisation (WHO) scale) Score 0 - 10, higher score described more progressed state	Day 28
Disease progression/improvement	proportion of patients with improved or progressed disease state (according to world health organisation (WHO) scale) Score 0 - 10, higher score described more progressed state	Day 28
Disease progression/improvement	Number of patients with each WHO score Score 0 - 10, higher score described more progressed state	Day 4
Disease progression/improvement	proportion of patients with each WHO score Score 0 - 10, higher score described more progressed state	Day 4
Disease progression/improvement	Number of patients with each WHO score Score 0 - 10, higher score described more progressed state	Day 7
Disease progression/improvement	proportion of patients with each WHO score Score 0 - 10, higher score described more progressed state	Day 7
Disease progression/improvement	Number of patients with each WHO score Score 0 - 10, higher score described more progressed state	Day 14
Disease progression/improvement	proportion of patients with each WHO score Score 0 - 10, higher score described more progressed state	Day 14
Disease progression/improvement	Number of patients with each WHO score Score 0 - 10, higher score described more progressed state	Day 28
Disease progression/improvement	proportion of patients with each WHO score Score 0 - 10, higher score described more progressed state	Day 28
Disease progression/improvement	WHO score and change to BL Score 0 - 10, higher score described more progressed state	Day 4
Disease progression/improvement	WHO score and change to BL Score 0 - 10, higher score described more progressed state	Day 7
Disease progression/improvement	WHO score and change to BL Score 0 - 10, higher score described more progressed state	Day 14
Disease progression/improvement	WHO score and change to BL Score 0 - 10, higher score described more progressed state	Day 28
Disease progression/improvement	Number of patients in each disease severity state according to WHO score Score 0 - 10, higher score described more progressed state	Day 4
Disease progression/improvement	proportion of patients in each disease severity state according to WHO score Score 0 - 10, higher score described more progressed state	Day 4
Disease progression/improvement	Number of patients in each disease severity state according to WHO score Score 0 - 10, higher score described more progressed state	Day 7
Disease progression/improvement	proportion of patients in each disease severity state according to WHO score Score 0 - 10, higher score described more progressed state	Day 7
Disease progression/improvement	proportion of patients in each disease severity state according to WHO score Score 0 - 10, higher score described more progressed state	Day 14
Disease progression/improvement	Number of patients in each disease severity state according to WHO score Score 0 - 10, higher score described more progressed state	Day 14
Disease progression/improvement	proportion of patients in each disease severity state according to WHO score Score 0 - 10, higher score described more progressed state	Day 28
Disease progression/improvement	Number of patients in each disease severity state according to WHO score Score 0 - 10, higher score described more progressed state	Day 28
Assessment of oxygen saturation	Oxygen saturation measured by finger clip and change to BL	Day 4
Assessment of oxygen saturation	Oxygen saturation measured by finger clip and change to BL	Day 7
Assessment of oxygen saturation	Oxygen saturation measured by finger clip and change to BL	Day 14
Assessment of oxygen saturation	Oxygen saturation measured by finger clip and change to BL	Day 28
Assessment of intake of concomitant medication	Type and average daily dose of concomitant medication and total dose of paracetamol	Day 14
Assessment of intake of concomitant medication	Average days of additional intake of concomitant medication paracetamol	Day 4
Assessment of intake of concomitant medication	Average days of additional intake of concomitant medication paracetamol	Day 7
Assessment of intake of concomitant medication	Average days of additional intake of concomitant medication paracetamol	Day 14
Assessment of intake of concomitant medication	Average days of additional intake of concomitant medication paracetamol	Day 28
Assessment of intake of concomitant medication	Number of patients with a reduction in concomitant medication intake	Day 14
Assessment of intake of concomitant medication	proportion of patients with a reduction in concomitant medication intake	Day 14
Number of patients with hyposmia or anosmia	Number of patients with hyposmia or anosmia	Day 4
proportion of patients with hyposmia or anosmia	proportion of patients with hyposmia or anosmia	Day 4
Number of patients with hyposmia or anosmia	Number of patients with hyposmia or anosmia	Day 7
proportion of patients with hyposmia or anosmia	proportion of patients with hyposmia or anosmia	Day 7
Number of patients with hyposmia or anosmia	Number of patients with hyposmia or anosmia	Day 14
proportion of patients with hyposmia or anosmia	proportion of patients with hyposmia or anosmia	Day 14
Number of patients with hyposmia or anosmia	Number of patients with hyposmia or anosmia	Day 28
proportion of patients with hyposmia or anosmia	proportion of patients with hyposmia or anosmia	Day 28
Number of patients with fever	Number of patients with fever	Day 4
proportion of patients with fever	proportion of patients with fever	Day 4
Number of patients with fever	Number of patients with fever	Day 7
proportion of patients with fever	proportion of patients with fever	Day 7
Number of patients with fever	Number of patients with fever	Day 14
proportion of patients with fever	proportion of patients with fever	Day 14
Number of patients with fever	Number of patients with fever	Day 28
proportion of patients with fever	proportion of patients with fever	Day 28
Number of patients with COVID-19 vaccination	Number of patients with COVID-19 vaccination	Day 4
proportions of patients with COVID-19 vaccination	proportions of patients with COVID-19 vaccination	Day 4
Number of patients with COVID-19 vaccination	Number of patients with COVID-19 vaccination	Day 7
proportions of patients with COVID-19 vaccination	proportions of patients with COVID-19 vaccination	Day 7
Number of patients with COVID-19 vaccination	Number of patients with COVID-19 vaccination	Day 14
proportions of patients with COVID-19 vaccination	proportions of patients with COVID-19 vaccination	Day 14
Number of patients with COVID-19 vaccination	Number of patients with COVID-19 vaccination	Day 28
proportions of patients with COVID-19 vaccination	proportions of patients with COVID-19 vaccination	Day 28
Number of recovered COVID-19 patients	Number of recovered COVID-19 patients	Day 4
proportion of recovered COVID-19 patients	proportion of recovered COVID-19 patients	Day 4
Number of recovered COVID-19 patients	Number of recovered COVID-19 patients	Day 7
proportion of recovered COVID-19 patients	proportion of recovered COVID-19 patients	Day 7
Number of recovered COVID-19 patients	Number of recovered COVID-19 patients	Day 14
proportion of recovered COVID-19 patients	proportion of recovered COVID-19 patients	Day 14
Number of recovered COVID-19 patients	Number of recovered COVID-19 patients	Day 28
proportion of recovered COVID-19 patients	proportion of recovered COVID-19 patients	Day 28
Assessment of severe acute respiratory syndrome (SARS)- Corona virus (CoV) -2 negativity	Assessment of SARS-CoV-2 negativity measured by polymerase chain reaction (PCR) test)	Day 4
Assessment of SARS-CoV-2 negativity	Assessment of SARS-CoV-2 negativity measured by polymerase chain reaction (PCR) test)	Day 7
Assessment of SARS-CoV-2 negativity	Assessment of SARS-CoV-2 negativity measured by polymerase chain reaction (PCR) test)	Day 14
Assessment of SARS-CoV-2 negativity	Assessment of SARS-CoV-2 negativity measured by polymerase chain reaction (PCR) test)	Day 28
Assessment of compliance	Compliance to investigational medicinal product (IMP) by dose taken and as documented in patient diary	Day 4
Assessment of compliance	Compliance to IMP by dose taken and as documented in patient diary	Day 7
Assessment of compliance	Compliance to IMP by dose taken and as documented in patient diary	Day 14
Number of adverse events (AE)	Number of adverse events (AE)	through study completion, average 28 days
Number of serious adverse events (SAE)	Number of serious adverse events (SAE)	through study completion, average 28 days
Type and severity of adverse events	Type and severity of adverse events	through study completion, average 28 days
Type and severity of serious adverse events	Type and severity of serious adverse events	through study completion, average 28 days
Seriousness and relatedness of AEs	Seriousness and relatedness of AEs	through study completion, average 28 days
Seriousness and relatedness of SAEs	Seriousness and relatedness of SAEs	through study completion, average 28 days

Collaborators and Investigators

• Sponsor: Dr. Frank Behrens
• Collaborators: Bionorica SE
• Investigators: Principal Investigator: Stephan Schaefer, MD, Fraunhofer ITMP

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 14, 2022
• Primary Completion (ANTICIPATED): October 31, 2022
• Study Completion (ANTICIPATED): November 30, 2022

Study Registration Dates

• First Submitted: March 2, 2022
• First Submitted That Met QC Criteria: March 10, 2022
• First Posted (ACTUAL): March 11, 2022

Study Record Updates

• Last Update Posted (ACTUAL): March 11, 2022
• Last Update Submitted That Met QC Criteria: March 10, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: COVID 19; ARDS; Bronchipret
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: TMP-2005-2020-36

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No