Phytomedicines Versus Hydroxychloroquine as an Add on Therapy to Azythromycin in Asymptomatic Covid-19 Patients

Study Overview
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Brief Summary
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Our previous work on plants has indicated significant antimalarial and antiviral activities. Of these plants, two recipes are proposed for evaluation for COVID-19. It is Cinchona, an antimalarial and a combination of 4 plants with antiviral, antimalarial, antitussive and anti-inflammatory properties. The phase II clinical trial, with three arms and at a rate of 77 patients per arm, received the approval of the National Committee for Ethics and Health Research. This is a non-inferiority test aimed at comparing the therapeutic impact in add on to Azithromycin, phytomedicines versus Hydroxychloroquine in asymptomatic COVID-19 patients. After 10 days of treatment, viral clearance and symptom progression will be assessed on days 3, 6 and 14. Clinical, paraclinical and laboratory tests will be performed throughout the 3-month trial. Ethical and deontological considerations will be applied

Detailed Description
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All consenting subjects who meet the inclusion criteria will benefit from an individual file which will include data relating to general information, the complete clinical examination and the paraclinical examination. They are distributed randomly into three parallel groups, each arm having a different treatment modality. A balanced randomization by permutation block of 5 will be applied using the Randomizer for Clinical Trial application developed by the company Medsharing). Laboratory examinations are carried out according to the procedures and method by laboratories accredited in Guinea for the diagnosis of COVID19. Data is encoded, entered and processed using statistical software. The comparison between the three cohorts will be made using either the Anova test for continuous variables or the chi-square test for categorical variables. The rate of change over time of virologic clearance, fever and other symptoms values as well as the differences for these rates between treatment arms will be tested using mixed-effects modeling. The biological samples will be stored at the biobank of the National Institute of Public Health of Guinea.

Official Title
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Evaluation de l'efficacité et de la tolérance de Quinquina et d'un phytomédicament  ACAR  en Comparaison Avec l'Hydroxychloroquine Chez Des Adultes Malades de Covid-19 Sans symptômes

Conditions
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Covid19

Intervention / Treatment
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* Combination Product: Hydroxychloroquine/Azithromycine
* Combination Product: Quinquina-Stevia/Azythromycin
* Combination Product: 4Plants/Azythromycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible patients are adults with COVID-19 confirmed by a positive PCR (Polymerase Chain Reaction) test and without symptoms Exclusion Criteria: any patient hypersensitive to hydroxychloroquine or under traditional herbal treatment in the two weeks preceding inclusion, any patient with other acute or chronic illnesses such as heart failure, arterial hypertension, renal failure, hepatocellular failure, tuberculosis or unable to take the oral treatment; any patient for whom one of the treatments under study is contraindicated according to the doctor's opinion. pregnant women, severe neurological manifestations

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Eligible consenting symptom-free patients with COVID-19 confirmed by a positive Polymerase Chain Reaction test were subjected to the 10 days of treatment allocated to each of the 3 arms of the trial. Virological clearance is assessed on days 3, 6 and 14. Side effects are noted throughout the trial period. Clinical, paraclinical and laboratory examinations are occasionally provided. Viral clearance, side effects, and the onset of COVID symptoms are evaluated and the data is statistically processed.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hydroxychloroquine/Azythromycin<br>Patients received Hydroxychloroquine 200 mg tablet orally 3 times daily for 10 days and Azythromycine 250 mg orally at the rate of 2 tablets the first day, then one tablet for 5 days | Combination Product: Hydroxychloroquine/Azithromycine<br>* Dual treatment with Hydroxychloroquine and Azythromycin<br>|
| Experimental: Quinquina/Azythromycin<br>Patients receive 3.5g tea bags of Cinchona/Stevia powder orally at the rate of 3 tea bags per day for 10 days | Combination Product: Quinquina-Stevia/Azythromycin<br>* Dual treatment with Quinquina/Stevia (3/0,5) and Azythromycin<br>* Other names: CILE;|
| Experimental: 4plants/Azythromycin<br>Participants received 4Plants powder in a 3.5g tea bag orally three times daily for 10 days and Azythromycine 250 mg orally at the rate of 2 tablets the first day, then one tablet for 5 days | Combination Product: 4Plants/Azythromycin<br>* Dual treatment with 4 plant species drug and Azythromycin<br>* Other names: ACAR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virologic clearance of throat swabs or lower respiratory tract secretions | Virologic clearance from admission to discharge at days 3, 6 and 14 | day 3 to day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| COVID-19 symptoms development | number of patients who developed fever, cough, and any other clinical sign typical of the disease | day 1 to day 14 | 
| Adverse effects | number of participants who developed treatment-related adverse effects | day 1 to day 14 | 
| Worsened condition | number of patients whose condition worsened on D14 | day 1 to day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment; clinical research