COVidIVERmectin: Ivermectin for Treatment of Covid-19

Study Overview
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Brief Summary
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Prospective, multi-centre, randomized, double-blind trial to assess efficacy and safety of ivermectin for the treatment of initial infection with SARS-CoV2 infection. Study arms: A) placebo B) ivermectin 600 μg/kg daily for 5 consecutive days (I_600) + placebo. C) ivermectin 1200 μg/kg daily at empty stomach with water for 5 consecutive days (I_1200). Patients will be randomized at emergency room of hospitals as well as at outpatient ambulatory care as well as at home, according to routine procedures of recruiting centres. In arm A and B, the number of placebo tablets to be administered will be calculated by the study dedicated pharmacist considering the number of tablets that should be taken in case a patient with the same weight is assigned to arm C.

Detailed Description
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Primary objectives The study is aimed: at defining if ivermectin, administered at dosage of 600 μg/kg or 1200 μg/kg QD for five consecutive days is safe in patients with initial, asymptomatic or oligosymptomatic SARS_CoV-2 infection, at defining if ivermectin, administered at the dosage(s) found to be safe decreases the viral load of SARS-CoV-2 at Day 7. Secondary objectives To assess the temporal profile of viral load at baseline, day 7, 14 and 30 the time to clinical cure (for symptomatic patients) the proportion of patients with virological clearance at day 14 and 30. the hospitalization rate. the COVID-19 Severity Score at day 14 and 30 STUDY DESIGN This is a multicentre, prospective, randomized, double-blind, adaptive phase II dose finding study. Patients meeting the inclusion criteria will be asked to participate to the study and randomized in a 1:1:1 ratio to either: Placebo arm (arm A): placebo will be identical in appearance to ivermectin in order to preserve blinding and will be administered p.o. at empty stomach with water once daily, for 5 days Intervention arms: a) Ivermectin, single dose 600 μg/kg, for 5 days (I_600) and placebo (arm B) ; b) Ivermectin, single dose 1200 μg/kg, for 5 days (I_1200) (arm C) ); these drugs will be administered p.o. once daily, for 5 days. In arm A and B, the number of placebo tablets to be administered will be calculated by the study dedicated pharmacist considering the number of tablets that should be taken in case a patient with the same weight is assigned to arm C. Patients will be randomized by a centralized computer system. At randomization a treatment ID is assigned to the patient. Once a treatment ID is assigned this must not be re-assigned even in cases of errors. Enrolled subjects will be identified by a unique subject number (patient code) that will remain consistent for the duration of the study. Patients will be recruited at the emergency room of hospitals, and/or among asymptomatic hospital workers found positive for SARS-CoV-2 at routine screening and/or in outpatient ambulatory settings, and/or at home, if not meeting the clinical criteria for hospitalization, according to the routine procedure of each participating site. The expected duration of subject inclusion in the study is of 1 month, or until the planned number of subjects to be enrolled will be reached.

Official Title
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Randomized, Double-blind, Multi Centre Phase II, Proof of Concept, Dose Finding Clinical Trial on Ivermectin for the Early Treatment of COVID-19

Conditions
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Covid19

Intervention / Treatment
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* Drug: Ivermectin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >=18 years Positivity at RT-PCR per SARS_CoV2 (nasopharyngeal swabs) Consent to participation to the study and to the processing of personal data COVID-19 Severity Score < 3 Patient able to take oral drugs Exclusion Criteria: Pregnant or lactating women (pregnancy test not required, if doubt patient is excluded) Subjects suffering from known CNS diseases Lack of (or inability to provide) informed consent Patient under dialysis Any severe medical condition with a prognosis of < 6 months Patients under warfarin treatment Patients under antiviral treatment Patients under chloroquine phosphate or hydroxychloroquine

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: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: I_600<br>ivermectin 600 μg/kg daily for 5 consecutive days (I_600) + placebo | Drug: Ivermectin<br>* Patients will be administered a single oral daily dose of approximately 600 μg/Kg (486-679 μg/Kg as rounded to a whole number of tablets), or 1200 μg/Kg (1098-1286 μg/Kg).<br>* Other names: Ivermectin 9 mg cp by Chemo group;|
| Experimental: I_1200<br>ivermectin 1200 μg/kg daily at empty stomach with water for 5 consecutive days | Drug: Ivermectin<br>* Patients will be administered a single oral daily dose of approximately 600 μg/Kg (486-679 μg/Kg as rounded to a whole number of tablets), or 1200 μg/Kg (1098-1286 μg/Kg).<br>* Other names: Ivermectin 9 mg cp by Chemo group;|
| Placebo Comparator: Placebo<br>placebo | Other: Placebo<br>* Patients should take placebo orally on an empty stomach with water<br>* Other names: Placebo supplied by chemo group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SADR | Number of serious adverse drug reaction | 14 days | 
| Viral load | Quantitative viral load as measured by quantitative, digital droplet PCR. | Assessed at day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trend viral load | 1. Trend over time of quantitative viral load at Day 7 and 14 as measured by quantitative, digital droplet PCR. | Days 7 and 14 from baseline | 
| Clinical resolution | Time to clinical resolution (for symptomatic patients). | Assessed on Day 30 | 
| Viral clearance | Time from diagnosis to documented viral clearance | assessed on days 14 and 30 | 
| Virological clearance | Proportion of patients with virological clearance | Assessed at day 14 and 30 | 
| hospitalization rate | rate of hospitalization | Day 30 | 
| Severity score | COVID-19 Severity Score (Coronavirus Diseases 19 Severity Score) - min value 1 (no limitation of activities), max value 8 (death). Higher scores mean worse outcome | Assessed at Day 14 and Day 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ivermectin