Evaluation of the Effects of Bradykinin Antagonists on Pulmonary Manifestations of COVID-19 Infections (AntagoBrad-Cov Study). (AntagoBrad)

The main objective of this study is to evaluate the efficacy of human C1 inhibitor, administered alone or in combination with icatibant (a specific bradykinin B2 receptor antagonist) on the pulmonary manifestations of COVID-19 infections.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Drug: C1 Inhibitor Human; Other: Placebo; Drug: Icatibant Injection

Detailed Description

Prospective, prospective, multicentre, double-blind, randomised, multi-centre study of three parallel groups of patients:

• Group 1 (n=15): standard of care + C1 inhibitor
• Group 2 (n=15): standard care + icatibant + C1 inhibitor
• Group 3 (n=15): standard support + placebo

The study has two parts:

• A 4-day (96-hour) therapeutic part during which the patient will be evaluated nine times (H0, H4, H12, H24, H36, H48, H60, H72 and H96).
• A follow-up part of 6 days with at least two assessments (D7 and D10).

The maximum duration of patient participation in the study will be 10 days.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Le Chesnay, France, 78150
    • Hôpital Privé de Parly II

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient over 18 years of age, having read and signed the consent form for participation in the study after the reflection period (≤ 15 minutes)
• Patient screened for COVID+ by RT-PCR on nasopharyngeal swab

• Patient with at least three of the following respiratory signs:

  • Temperature >38° C
  • Non-productive dry cough
  • Presence of crackling rales on auscultation
  • Respiratory discomfort felt by the patient
  • Heart rate > 90/min
  • Respiratory rate >20/min
  • O2 saturation ≤ 93%
• Patient whose clinical condition, in the opinion of the investigator, requires hospital monitoring.
• Patient who would have been monitored and treated outside of study participation, including prevention of thromboembolic risk with LMWH.

Exclusion Criteria:

• Patient with pre-existing respiratory disease (cancer, COPD, asthma, emphysema) or smoking history of > 25 years)
• Patient with a known allergy to one of the study products
• Patient treated with anti TNF, IL1 or IL6
• Patient requiring immediate intubation
• Patient on a low sodium diet
• Patient under protective custody, guardianship or trusteeship
• Patient not affiliated to the French social security system
• Patient participating in another therapeutic protocol
• Pregnant or likely to become pregnant (woman of childbearing age without effective contraception and without HCG dosage)
• Patient unable to understand informed information and/or give written informed consent: dementia, psychosis, consciousness disorders, non-French speaking patient

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: standard care + C1 inhibitor; The C1 inhibitor will be used at a dose of 1000 units per slow infusion (two hours). Two infusions will be given 24 hours apart. These doses correspond to the usual doses used in the treatment of conditions in which the C1-Inhibitor is indicated.	Drug: C1 Inhibitor Human; standard care + 1000 units of C1 inhibitor during 2 slow infusions of 500 units; Other: Placebo; The placebo will be physiological serum presented in forms mimicking the C1-Inhibitor and the icatibant.
Experimental: standard care + Icatibant + C1 inhibitor; The C1 inhibitor will be used at a dose of 1000 units per slow infusion (two hours). Two infusions will be given 24 hours apart. These doses correspond to the usual doses used in the treatment of conditions in which the C1-Inhibitor is indicated. The icatibant will be used in a single injection of 30 mg subcutaneously, preferably in the abdominal region. These doses correspond to the doses usually used in the treatment of conditions in which icatibant is indicated.	Drug: C1 Inhibitor Human; standard care + 1000 units of C1 inhibitor during 2 slow infusions of 500 units; Drug: Icatibant Injection; a single injection of 30 mg subcutaneously
Placebo Comparator: standard care + placebo	Other: Placebo; The placebo will be physiological serum presented in forms mimicking the C1-Inhibitor and the icatibant.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy evaluation respiratory discomfort	To evaluate the efficacy of human C1 inhibitor, administered alone or in combination with icatibant (a specific bradykinin B2 receptor antagonist) on the pulmonary manifestations of COVID-19 infections. The evaluation of the treatment efficacy of the study is based on the clinical monitoring of the patient and particularly on the following combination of criteria as experienced by the patient : no respiratory discomfort; heart rate between 60 and 90 /min; respiratory rate less than 20/min; O2 saturation greater than 94% without oxygen supply	96 hours after the administration of treatment
Efficacy evaluation heart rate between 60 and 90 /min	To evaluate the efficacy of human C1 inhibitor, administered alone or in combination with icatibant (a specific bradykinin B2 receptor antagonist) on the pulmonary manifestations of COVID-19 infections. The evaluation of the treatment efficacy of the study is based on the clinical monitoring of the patient and particularly on the following combination of criteria as experienced by the patient : no respiratory discomfort; heart rate between 60 and 90 /min; respiratory rate less than 20/min; O2 saturation greater than 94% without oxygen supply	96 hours after the administration of treatment
Efficacy evaluation respiratory rate less than 20/min	To evaluate the efficacy of human C1 inhibitor, administered alone or in combination with icatibant (a specific bradykinin B2 receptor antagonist) on the pulmonary manifestations of COVID-19 infections. The evaluation of the treatment efficacy of the study is based on the clinical monitoring of the patient and particularly on the following combination of criteria as experienced by the patient : no respiratory discomfort; heart rate between 60 and 90 /min; respiratory rate less than 20/min; O2 saturation greater than 94% without oxygen supply	96 hours after the administration of treatment
Efficacy evaluation O2 saturation greater than 94% without oxygen supply	To evaluate the efficacy of human C1 inhibitor, administered alone or in combination with icatibant (a specific bradykinin B2 receptor antagonist) on the pulmonary manifestations of COVID-19 infections. The evaluation of the treatment efficacy of the study is based on the clinical monitoring of the patient and particularly on the following combination of criteria as experienced by the patient : no respiratory discomfort; heart rate between 60 and 90 /min; respiratory rate less than 20/min; O2 saturation greater than 94% without oxygen supply	96 hours after the administration of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerance evaluation	The tolerance of the study products will be assessed by collecting adverse events that occurred during the study period.	Day 10

Collaborators and Investigators

• Sponsor: GCS Ramsay Santé pour l'Enseignement et la Recherche
• Investigators: Study Director: Denis VINCENT, MD PD, Médecine interne, Faculté de Montpellier

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2021
• Primary Completion (Actual): June 13, 2021
• Study Completion (Actual): June 21, 2021

Study Registration Dates

• First Submitted: August 16, 2021
• First Submitted That Met QC Criteria: August 17, 2021
• First Posted (Actual): August 18, 2021

Study Record Updates

• Last Update Posted (Estimate): December 22, 2022
• Last Update Submitted That Met QC Criteria: December 20, 2022
• Last Verified: August 1, 2021

More Information

Terms related to this study

• 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Bradykinin B2 Receptor Antagonists; Bradykinin Receptor Antagonists; Complement C1 Inhibitor Protein; Icatibant
• Other Study ID Numbers: 2020-002225-29

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No