Back to resultsStudy to Verify the Effectiveness and Safety of Isothymol or Carvacrol Compound Against SARS-CoV-2 in COVID-19 Patients
Primary Purpose
COVID-19, COVID-19 Pneumonia, COVID-19 Respiratory Infection
Status
Completed
Phase
Phase 2
Locations
Venezuela
Study Type
Interventional
Intervention
Carvacrol
Control group
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19 focused on measuring SARS-CoV-2, Isothymol, Carvacrol, Antiviral, COVID-19, RNA, Cytokine storm
Eligibility Criteria
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:
- Positive test PDR, positive test RT-PCR, patients diagnosed with COVID-19
- Chest pain or other symptom consistent with bilateral pneumonia atypical, with one of the following paraclinical alterations and imaging:
- Oxygen saturation (SpO2) ≤93%.
- Elevation of D-dimer ≥10 mg/mL.
- Elevation of Ferritin ≥120 ng/mL.
- Elevation of Fibrinogen ≥400 mg/dL
- Elevation of Immunoglobulin M (IgM) ≥200 mg/dL.
- Elevation of Interleukin 6 (IL-6) ≥1800 pg/mL.
- 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).
Sites / Locations
- Hospital Dr. Leopoldo Manrique Terrero - Periférico de Coche.
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Isothymol or Carvacrol group
Control
Arm Description
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%).
•Placebo
Outcomes
Primary Outcome Measures
Mortality Rate Among COVID-19 Patients
The incidence of mortality in the first 15 days.
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
Quantitative Evaluation of Immunoglobulin M (IgM) by test ELISA as Collected Over Time to Day 15
IgM in mg/dl
Quantitative Evaluation of Immunoglobulin G (IgG) by test ELISA as Collected Over Time to Day 15
IgG in mg/dl
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.
Requirement for Extracorporeal Membrane Oxygenation (ECMO) in COVID-19 Patients Over Time to Day 15
A measure of disease morbidity.
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT05445089
First Posted
June 21, 2022
Last Updated
July 5, 2022
Sponsor
Instituto Venezolano de Investigaciones Cientificas
1. Study Identification
Unique Protocol Identification Number
NCT05445089
Brief Title
Study to Verify the Effectiveness and Safety of Isothymol or Carvacrol Compound Against SARS-CoV-2 in COVID-19 Patients
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
August 1, 2020 (Actual)
Primary Completion Date
November 1, 2020 (Actual)
Study Completion Date
December 15, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Instituto Venezolano de Investigaciones Cientificas
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
• Check the efficacy, safety and tolerability of the compound Modified isothymol against the SARS-CoV-2 agent in patients COVID-19.
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19, COVID-19 Pneumonia, COVID-19 Respiratory Infection, COVID-19 Acute Respiratory Distress Syndrome, COVID-19 Lower Respiratory Infection
Keywords
SARS-CoV-2, Isothymol, Carvacrol, Antiviral, COVID-19, RNA, Cytokine storm
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Randomized, double-blind, multicenter study with blind evaluation of events, designed to compare the efficacy and safety of Isothymol modified with placebo in patients ≥18 years of age who meet the inclusion criteria.
Drug administration scheme: Randomized and parallel (modified isothymol and placebo).
Statistical design: Superiority. It will allow to detect difference between drug and placebo after parallel administration.
Masking
Participant
Masking Description
The assigned treatment will not be known to the study subjects, the participating researchers and the evaluators of the criteria of study assessment. The placebo should contain the same technical specifications and physical appearance of modified Isothymol.
To ensure individual opening of the randomization code, sealed envelopes will be prepared for each subject, which will contain the specific treatment received by each. These envelopes can be controlled by the Clinical Researcher, the Nursing Staff or Pharmacy available 24 hours.
After obtaining informed consent, the treatment strategy uses centralized randomization, using a phone system. Eligible patients will be randomized to one of the following therapeutic strategies:
Modified Isothymol Treatment Group: Immediately after randomization a dose of 6 mg/ml of modified isothymol.
Placebo Treatment Group: Immediately after the randomization a placebo dose will be administered.
Allocation
Randomized
Enrollment
600 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Isothymol or Carvacrol group
Arm Type
Experimental
Arm Description
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%).
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
•Placebo
Intervention Type
Drug
Intervention Name(s)
Carvacrol
Other Intervention Name(s)
CARVATIVIR
Intervention Description
Carvativir 6 mg/ml diluted for oral solution.
Intervention Type
Other
Intervention Name(s)
Control group
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Mortality Rate Among COVID-19 Patients
Description
The incidence of mortality in the first 15 days.
Time Frame
Day 1 to Day 15
Title
Quantitative Evaluation of Inflammatory Mediator Interleukin 6 (IL-6) by test ELISA as Collected Over Time to Day 15
Description
Interleukin 6 (IL-6) in pg/ml
Time Frame
Day 1 to Day 15
Title
Quantitative Evaluation of Immunoglobulin M (IgM) by test ELISA as Collected Over Time to Day 15
Description
IgM in mg/dl
Time Frame
Day 1 to Day 15
Title
Quantitative Evaluation of Immunoglobulin G (IgG) by test ELISA as Collected Over Time to Day 15
Description
IgG in mg/dl
Time Frame
Day 1 to Day 15
Title
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
Description
As a measure of disease acuity and severity.
Time Frame
Day 1 to Day 15
Title
Requirement for Extracorporeal Membrane Oxygenation (ECMO) in COVID-19 Patients Over Time to Day 15
Description
A measure of disease morbidity.
Time Frame
Day 1 to Day 15
Secondary Outcome Measure Information:
Title
Longitudinal Assessment of Viral Load by Semi-Quantitative Polymerase Chain Reaction (PCR) Over Time to Day 15
Description
Ribonucleic acid (RNA) from the nasal swab will be used to assess SARS-CoV-2 viral load.
Time Frame
Day 1 to Day 15
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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:
Positive test PDR, positive test RT-PCR, patients diagnosed with COVID-19
Chest pain or other symptom consistent with bilateral pneumonia atypical, with one of the following paraclinical alterations and imaging:
Oxygen saturation (SpO2) ≤93%.
Elevation of D-dimer ≥10 mg/mL.
Elevation of Ferritin ≥120 ng/mL.
Elevation of Fibrinogen ≥400 mg/dL
Elevation of Immunoglobulin M (IgM) ≥200 mg/dL.
Elevation of Interleukin 6 (IL-6) ≥1800 pg/mL.
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Raul Ojeda, MsC
Organizational Affiliation
Biosynthesis Medical
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Dr. Leopoldo Manrique Terrero - Periférico de Coche.
City
Caracas
State/Province
Miranda
ZIP/Postal Code
1090
Country
Venezuela
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://doi.org/10.1186/ISRCTN15363958
Description
Study to verify the effectiveness and safety of the modified isothymol or carvacrol compound against SARS-CoV-2 in COVID-19 patients
Learn more about this trial
Study to Verify the Effectiveness and Safety of Isothymol or Carvacrol Compound Against SARS-CoV-2 in COVID-19 Patients
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