Ivermectin to Prevent Hospitalizations in COVID-19

Study Overview
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Brief Summary
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It is a single-center, prospective, randomized, double-blind, placebo-controlled study carried out by the Ministry of Public Health of the Province of Corrientes, Argentina, in coordination with the Corrientes Institute of Cardiology Juana F. Cabral. Patients who meet all the inclusion criteria and none of the exclusion criteria are randomized via the web system to receive placebo or ivermectin. The need for hospitalization in patients with COVID-19 is assessed as the primary end point. As secondary end points are evaluated: time to hospitalization (in days); use of invasive mechanical ventilation; time to invasive mechanical ventilation (in days); dialysis; all-cause mortality; negative of the swab at 3 ± 1 days and 12 ± 2 days after entering the study and ivermectin safety. Intermediate internal analyzes of study objectives and serious adverse events will be performed, including 125; 250 and 375 patients in order to assess the possible need for early termination of the study. For these intermediate internal analyzes, the Haybittle-Peto rule will be followed, therefore a value of p <0.001 will be considered significant

Detailed Description
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The study will be carried out in the province of Corrientes, in the Argentine Republic. All patients must be domiciled in this province. In the province of Corrientes, the care of patients with COVID19 is in charge of a single group of professionals (Crisis Committee) and patients who require hospitalization will be carried out in a single hospital destined for this purpose

Official Title
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Ivermectin to Prevent Hospitalizations in COVID-19: Randomized, Double-blind, Placebo-controlled

Conditions
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Covid19

Intervention / Treatment
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* Drug: Ivermectin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Over 18 years of age who reside in the province of Corrientes at the time of diagnosis; Confirmed diagnosis of COVID-19 by polymerase chain reaction test for detection of SARS-CoV2 in the last 48 hours; In the case of women of childbearing age, they must be using a contraceptive method of proven efficacy and safety (barrier, hormonal or permanent contraceptives) for at least 3 months prior to inclusion in the present study and for the entire period of time for the duration of the study and until at least 30 days after the end of this study. A woman will be considered to have no reproductive capacity if she is postmenopausal (at least 2 years without her menstrual cycles) or if she has undergone surgical sterilization (at least one month before the time of inviting her to participate in this study); Weight at the time of inclusion greater than 48,000 kilograms; That they sign the informed consent for participation in the study. Exclusion Criteria: Pregnant or breastfeeding women; Known allergy to ivermectin or some of the components of ivermectin tablets or placebo; Current use of home oxygen; That require hospitalization due to COVID-19 at the time of diagnosis or history of hospitalization for COVID-19; Presence of mal-absorptive syndrome; Presence of any other concomitant acute infectious disease; Known history of severe liver disease, for example liver cirrhosis; Need or use of antiviral drugs at the time of admission for another viral pathology other than COVID-19; Need or use of hydroxychloroquine or chloroquine; Use of ivermectin up to 7 days prior to randomization; Patients on dialysis or who have required it in the last 2 months or who plan to do it in the next 2 months; Current participation or in the last 30 days in a research study that has included the administration of a drug.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ivermectin<br>The dose of ivermectin in patients who are randomized to the active substance depends on the weight of the patient: More than 48 kg and less than 80 kg: Two tablets of 6 mg each (12 mg in total) at the time of inclusion and the same dose at 24 hours. More than 80 kg and less than 110 kg: Three tablets of 6 mg each (18 mg in total) at the time of inclusion and the same dose at 24 hours. More than 110 Kg: Four tablets of 6 mg each (24 mg in total) at the time of inclusion and the same dose at 24 hours. | Drug: Ivermectin<br>* Patients will receive the tablet from the branch to which they were randomized only at the time of inclusion and 24 hours after the first dose.<br>|
| Placebo Comparator: Placebo<br>The dose of placebo in patients who are randomized to the this depends on the weight of the patient: More than 48 kg and less than 80 kg: Two tablets of 6 mg each (12 mg in total) at the time of inclusion and the same dose at 24 hours. More than 80 kg and less than 110 kg: Three tablets of 6 mg each (18 mg in total) at the time of inclusion and the same dose at 24 hours. More than 110 Kg: Four tablets of 6 mg each (24 mg in total) at the time of inclusion and the same dose at 24 hours. | Drug: Placebo<br>* Patients will receive the tablet from the branch to which they were randomized only at the time of inclusion and 24 hours after the first dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Hospitalization of medical cause in patients with COVID-19 in each arm | Hospitalization will be considered when at least 24 hours have elapsed in a health institution, in any of its services. | through study completion, an average of 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to hospitalization | Number of days elapsed | through study completion, an average of 30 days | 
| Percentage of Use of invasive mechanical ventilation support in each arm | All patients who are connected to invasive mechanical ventilation support | through study completion, an average of 30 days | 
| Time to invasive mechanical ventilation support | Number of days elapsed | through study completion, an average of 30 days | 
| Percentage of dialysis in each arm | All patients who require temporary or permanent renal replacement therapy | through study completion, an average of 30 days | 
| All-cause mortality | Death of the patient, from any cause. | through study completion, an average of 30 days | 
| Negative of the swab at 3±1 days and 12±2 days after entering the study | Negative Nasal Swab Using Polymerase Chain Reaction Technique | At days 3±1 and 12±2 | 
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]) | According to the adverse events that patients may present. | through study completion, an average of 30 days | 

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