Ivermectin vs Combined Hydroxychloroquine and Antiretroviral Drugs (ART) Among Asymptomatic COVID-19 Infection

Study Overview
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Brief Summary
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This is an open label randomised controlled study of oral ivermectin (600 mcg/kg/d* 3 day) versus combined of hydroxychloroquine plus darunavir/ ritonavir for 5 days treatment among asymptomatic carrier of SAR-CoV2 adult Thai population. Both study treatment regimens will have oral zinc sulfate combination treatment ( 200mg. twice daily). Outcomes include safety and duration of detectable of SAR-CoV2 in nasopharyngeal/ throat (NP) swab by polymerase chain reaction amplification (PCR) after treatment. 40-50 patients in each treatment arm is planned, with an interim analysis when approximately 50% of cases is enrolled.

Detailed Description
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Study procedure will be carried out after informed consent is obtained. Baseline physical exam and laboratory investigations will be performed. Eligible patients will be randomized to one of the two treatment arms. Symptoms and signs will be monitored daily. NP swab will be done at day5-7, and prior to discharge. Complete blood counts, blood chemistries, electrocardiography will be performed for adverse event monitoring within 5 days after end of study drugs' administration. Patients will be discharged at 2- 4 weeks after hospitalization, according to PCR results. There will be 1-2 follow up visit at out patient clinic for NP swab (patients with +ve last NP swab before discharge), and blood tests. Additional 5-8 ml. of EDTA blood will be taken at baseline and weekly for antibody detection. Interim analysis of both safety and efficacy will be performed when approximately 50% of enrollment is achieved. Intention to treat analysis is planned at the completion of enrollment.

Official Title
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Comparative Efficacy of Ivermectin Versus Combination of Hydroxychloroquine Plus Darunavir/ Ritonavir for Shortening Duration of SARS-CoV2 Detection From Respiratory Secretion Among Asymptomatic or Afebrile COVID-19 Infection

Conditions
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Asymptomatic Infections, SARS-CoV2 Infection

Intervention / Treatment
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* Drug: Ivermectin Pill
* Drug: Combined ART/hydroxychloroquine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: SAR-CoV2 detected by PCR from NP swab Asymptomatic or upper respiratory symptoms such as runny noses No history of fever or oral Temp <37.8 degree celsius informed consent obtained Exclusion Criteria: Fever or respiratory rate >24/minute or oxygen saturation at room air< 94% Any serious co-morbidity such as chronic lung disease, chronic kidney disease, cardiovascular diseases, arrythmia, diabetes mellitus with HbA1C > 8%, chronic liver disease, lymphocyte count <1,000cell/cu.mm. History of ivermectin or any of the study drug allergy. Concomitant medication with potential drug interaction with any of the study drugs such as alfuzosin, colchicine, ergot derivatives, cisapride, simvastatin and rifampicin Pregnant or lactating woman

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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ivermectin<br>Combination of oral ivermectin 600 mcg/kg/day once daily for 3 days Zinc sulfate (100mg/tab) 2 tab every 12 hours for 3 days | Drug: Ivermectin Pill<br>* 3 days of once daily oral ivermectin 600mcg/kg/d<br>* Other names: Vermectin;|
| Active Comparator: ART/hydroxychloroquine<br>Combination of Day1 hydroxychloroquine 400mg bid, then 200mg bid on Day 2-5 Darunavir/ritonavir (400/100mg) every 12 hours for 5 days Zinc sulfate (100/tab) 2 tab every 12 hours for 5 days | Drug: Combined ART/hydroxychloroquine<br>* Day 1 hydroxychloroquine 400mg bid, Day2-5 hydroxychloroquine 200mg bid Darunavir/ritonavir (400/100mg) q 12 hours for 5 days<br>* Other names: combined darunavir/ritonavir/hydroxychloroquine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse event rates | Comparison of adverse event rates between treatment arms | after first dose until day 28 of follow up | 
| Efficacy for shortening duration of SAR-CoV2 detection by PCR | comparison of median duration for detectable SAR-CoV2 by PCR from NP swab in each arm | weekly after treatment until 4th week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody detection rates | comparison of median duration for total antibody detection in each arm | weekly after treatment until 4th week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ivermectin, hydroxychloroquine/darunavir/ritonavir, SAR-CoV2, asymptomatic infection, zinc sulfate