Study to Verify the Effectiveness and Safety of Isothymol or Carvacrol Compound Against SARS-CoV-2 in COVID-19 Patients

Multicenter, Randomized, Double-blind Study With Placebo to Verify the Efficacy, Safety and Tolerability of the Modified Isothymol or Carvacrol Compound Against the SARS-CoV-2 Agent in COVID-19 Patients

• Check the efficacy, safety and tolerability of the compound Modified isothymol against the SARS-CoV-2 agent in patients COVID-19.

Study Overview

• Status: Completed
• Conditions: COVID-19; COVID-19 Pneumonia; COVID-19 Respiratory Infection; COVID-19 Acute Respiratory Distress Syndrome; COVID-19 Lower Respiratory Infection
• Intervention / Treatment: Drug: Carvacrol; Other: Control group

Detailed Description

• Evaluate the inhibition of the terminal glycosylation of the Enzyme Angiotensin II converter (ECE2).
• Check the inhibition of the main protease function (Mpro) of the SARS-CoV-2 agent by stable binding of the drug/protein to control viral replication.
• Check the oxidation reaction of the amine R-CH2-NH2 involved in the hyperactivation of macrophages (immune system innate), by interference of modified Isothymol.
• Evaluate the increase in tolerance to hypersensitivity of the immunoglobulins G (IgG) and immunoglobulins M (IgM) in patients COVID-19.
• Check the suppression of production and adhesion of superoxides in neutrophils (Immunostimulatory effect) through the regulation of cytokines and IL-6 (interleukins) for the inhibition of cytokine storm (Stage 2 and 3, infected patient).

• Study Type: Interventional
• Enrollment (Actual): 600
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Venezuela
  • Miranda
    • Caracas, Miranda, Venezuela, 1090
      • Hospital Dr. Leopoldo Manrique Terrero - Periférico de Coche.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

The study population will be patients aged ≥18 years with RT-PCR positive (detection of genetic material from SARS-CoV-2 in the analyzed sample), eligible for COVID-19, who attend a center physician with an active primary care program, in the early hours from the onset of symptoms. In the case of asymptomatic the analysis of the nasopharyngeal swab will be verified in the triage, and in Depending on the result, they may or may not be included in the clinical protocol.

A sample size of 600 patients is expected, which must be randomize for parallel administration of experimental drug (300 patients) and placebo (300 patients).

It should be evaluated prior to the start of the clinical trial: Tests of rapid diagnosis (PDR test), chain reaction of the Reverse Transcriptase Polymerase (RT-PCR test), pressure blood pressure, pulse, temperature, body weight, blood tests, detection of autoimmune and infectious diseases (HIV, lupus, rheumatoid arthritis, hepatitis, syphilis), detection of antibodies (immunoglobulin G and immunoglobulin and M), urine tests for detect drugs and pregnancy (in the case of women) and other comorbid conditions characterized. In addition, chest x-ray should be performed on each patient included in the test, and if possible perform a computerized tomography (before and after treatment with modified Isothymol).

There will be an electronic system to load all the variables scientific and clinical protocol established in data collection, and will also allow processing of expedited output variables, which can be audited in real time.

Participant inclusion criteria:

1. Positive test PDR, positive test RT-PCR, patients diagnosed with COVID-19
2. Chest pain or other symptom consistent with bilateral pneumonia atypical, with one of the following paraclinical alterations and imaging:
3. Oxygen saturation (SpO2) ≤93%.
4. Elevation of D-dimer ≥10 mg/mL.
5. Elevation of Ferritin ≥120 ng/mL.
6. Elevation of Fibrinogen ≥400 mg/dL
7. Elevation of Immunoglobulin M (IgM) ≥200 mg/dL.
8. Elevation of Interleukin 6 (IL-6) ≥1800 pg/mL.
9. Rx. chest and CT showing thickening of the bronchi, consolidation and ground glass opacities.

Participant exclusion criteria:

Negative test PDR, negative test RT-PCR and Inadequate administration of antiviral (for non-compliance with indicated intervals or death of the patient before 15 days treatment indications).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Isothymol or Carvacrol group; Each ml contains 6mg of Isothymol or Carvacrol (2-Methyl-5-(1-methylethyl)-phenol modified) at 1% v/v. (GRAS lipophilic modified with isothymol).; Oral solution (dispersion L/L). Dilute lipophilic aqueous solution of light or medium yellow.; Excipients: Cis-9-octadecenoic acid with Squalene (99%).	Drug: Carvacrol; Carvativir 6 mg/ml diluted for oral solution.; Other Names: CARVATIVIR
Placebo Comparator: Control; •Placebo	Other: Control group; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality Rate Among COVID-19 Patients	The incidence of mortality in the first 15 days.	Day 1 to Day 15
Quantitative Evaluation of Inflammatory Mediator Interleukin 6 (IL-6) by test ELISA as Collected Over Time to Day 15	Interleukin 6 (IL-6) in pg/ml	Day 1 to Day 15
Quantitative Evaluation of Immunoglobulin M (IgM) by test ELISA as Collected Over Time to Day 15	IgM in mg/dl	Day 1 to Day 15
Quantitative Evaluation of Immunoglobulin G (IgG) by test ELISA as Collected Over Time to Day 15	IgG in mg/dl	Day 1 to Day 15
Proportion of Patients with COVID-19 who Require Intensive Care Unit (ICU)-Level Care, Mechanical Ventilatory Support (MV), and/or Extracorporeal Membrane Oxygenation (ECMO) Over Time to Day 15	As a measure of disease acuity and severity.	Day 1 to Day 15
Requirement for Extracorporeal Membrane Oxygenation (ECMO) in COVID-19 Patients Over Time to Day 15	A measure of disease morbidity.	Day 1 to Day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Longitudinal Assessment of Viral Load by Semi-Quantitative Polymerase Chain Reaction (PCR) Over Time to Day 15	Ribonucleic acid (RNA) from the nasal swab will be used to assess SARS-CoV-2 viral load.	Day 1 to Day 15

Collaborators and Investigators

• Sponsor: Instituto Venezolano de Investigaciones Cientificas
• Investigators: Principal Investigator: Raul Ojeda, MsC, Biosynthesis Medical

Publications and helpful links

Helpful Links

• Study to verify the effectiveness and safety of the modified isothymol or carvacrol compound against SARS-CoV-2 in COVID-19 patients

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2020
• Primary Completion (Actual): November 1, 2020
• Study Completion (Actual): December 15, 2020

Study Registration Dates

• First Submitted: June 21, 2022
• First Submitted That Met QC Criteria: June 30, 2022
• First Posted (Actual): July 6, 2022

Study Record Updates

• Last Update Posted (Actual): July 8, 2022
• Last Update Submitted That Met QC Criteria: July 5, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; Antiviral; Cytokine storm; RNA; Isothymol; Carvacrol
• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; COVID-19; Infections; Communicable Diseases; Respiratory Tract Infections; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: LAB-2020-01; ISRCTN registry (Registry Identifier: ISRCTN15363958)

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