A Study to Compare the Efficacy and Safety of Different Doses of Ivermectin for COVID-19

Study Overview
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Brief Summary
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In December 2019, a group of patients with pneumonia of unknown cause was linked to a wholesale seafood market in Wuhan, China. The genetic analysis of samples from the lower respiratory tract of these patients indicated a new coronavirus as the causative agent, which was named SARS-CoV-2. The virus spread rapidly to more than 45 countries, including Brazil, causing an international alarm. However, in spite of its epidemiological magnitude, so far, there is no antiviral treatment or vaccine approved for the treatment of this infection. With about 15% to 20% of SARS-CoV-2 patients suffering from serious illnesses and overburdened hospitals, therapeutic options are desperately needed. So, instead of creating compounds from scratch that can take years to develop and test, researchers and public health agencies have sought to redirect drugs already approved for other diseases and known to be widely safe. In this context, the analysis of the international literature shows the existence of an in vitro antiviral activity of ivermectin against SARS-CoV-2. However, there are no studies that have evaluated its clinical effectiveness in patients diagnosed with SARS-CoV-2 infection. Therefore, and considering this knowledge gap, the present study aims to determine the clinical efficacy and safety of different doses of ivermectin in patients diagnosed with SARS-CoV-2 infection.

Official Title
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Phase 2 Clinical Trial to Compare the Efficacy and Safety of Different Doses of Ivermectin in Patients Diagnosed With the New Coronavirus Infection (SARS-CoV-2)

Conditions
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Coronavirus Infection

Intervention / Treatment
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* Drug: Ivermectin
* Other: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of infection by SARS-CoV-2: symptoms of acute respiratory tract infection (sudden onset of at least one of the following: cough, fever, shortness of breath) and biomolecular diagnosis of SARS-CoV-2 infection; OR any acute respiratory disease AND biomolecular diagnosis of SARS-CoV-2 infection; OR severe acute respiratory infection (fever and at least one sign / symptom of respiratory disease eg cough, fever, shortness of breath) AND in need of hospitalization AND biomolecular diagnosis of SARS-CoV-2 infection; Eastern Cooperative Oncology Group Performance Status score 0 to 1; National Early Warning Score 0 to 4; Ability to understand and consent to participate in this clinical trial, manifested by signing the Informed Consent Form (ICF). Exclusion Criteria: Inability to ingest / absorb the study drug orally through spontaneous ingestion or use of gastro / enteral tubes; Any finding of clinical observation (history / physical evaluation) that is interpreted by the investigating physician as a risk to participate in the trial; Any laboratory test findings that the investigating physician considers as a risk to the research participant as to his / her participation in the clinical study; Any ECG examination finding that the investigating physician considers as a risk to the research participant as to his / her participation in the trial; Known hypersensitivity to the components of the drugs used during the study; Women in pregnancy or breastfeeding; Body weight less than 15kg; Estimated glomerular filtration rate (CKD-Epidemiology Collaboration, CKD-EPI) <30 mL / min; Aspartate aminotransaminase (AST) or alanine aminotransaminase (ALT)> 5 times the upper limit of normality; Refusal to participate; Refusal to sign the informed consent form.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of care<br>Standard of care (SOC) treatment | Other: Standard of Care<br>* Standard treatment for COVID-19<br>|
| Experimental: SOC plus ivermectin 100 mcg/kg<br>SOC plus ivermectin 100 mcg/kg | Drug: Ivermectin<br>* SOC plus different dosing regimens of Ivermectin<br>|
| Experimental: SOC plus ivermectin 200 mcg/kg<br>SOC plus ivermectin 200 mcg/kg | Drug: Ivermectin<br>* SOC plus different dosing regimens of Ivermectin<br>|
| Experimental: SOC plus ivermectin 400 mcg/kg<br>SOC plus ivermectin 400 mcg/kg | Drug: Ivermectin<br>* SOC plus different dosing regimens of Ivermectin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Undetectable viral load during 7 days of follow-up. | Proportion of patients who achieved undetectable viral load during 7 days of follow-up. | 7 days following intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viral load variation in the nasopharyngeal swab. | Viral load variation in the nasopharyngeal swab during treatment. | 7 days following intervention. | 
| Time to undetectable SARS-CoV-2 viral load in the nasopharyngeal swab. | Variation of serum lymphocyte counts during treatment. | 7 days following intervention. | 
| Incidence of Treatment-Emergent Self-reported Adverse Events | Incidence of Treatment-Emergent Adverse Events as assessed by clinical history and physical examination | 28 days following intervention. | 
| Incidence of Treatment-Emergent Laboratory-based Adverse Events | Incidence of Treatment-Emergent Adverse Events as assessed by laboratory tests | 28 days following intervention. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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coronavirus infections, SARS-CoV-2, COVID-19, ivermectin, clinical trial