Chloroquine + Losartan Compared to Chloroquine Alone for the Treatment of COVID-19 Pneumonia

Study Overview
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Brief Summary
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Study design Phase 2, double blinded, single-center, 1:1 randomized clinical trial of Chloroquine vs Chloroquine/losartan for the treatment of SARS-CoV-2 pneumonia in non-critically ill subjects

Detailed Description
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Study design Phase 2, blinded, single-center, 1: 1 randomized clinical trial for the treatment of SARS-CoV-2 pneumonia in non-critically ill subjects. Two of the co-investigators and the data analyst will remain blind to group allocation until after statistical analysis. The groups will consist of subjects receiving in one arm PO Chloroquine 450mg every 12 hours and in the other arm, in addition to chloroquine, PO Losartan 25mg every 24 hours. Study drugs will be administered for a total of 10 days enterally. Baseline demographics and clinical characteristics will be registered and periodically during the study. nasopharyngeal swabs will be taken every 48hrs during hospitalization to determine the presences and viral load of SARS-CoV-2, and daily EKG for QT interval monitoring.

Official Title
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Phase II, Randomized, Double-blind, Controlled Clinical Trial Evaluating the Efficacy and Safety of Chloroquine + Low Dose Losartan Compared to Chloroquine Monotherapy in Subjects With SARS-CoV-2 Pneumonia

Conditions
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COVID-19 Pneumonia

Intervention / Treatment
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* Drug: Chloroquine Phosphate Tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women ≥18 years. Oral tolerance or access for enteral administration of medication. PCR or IgM for SARS-CoV-2 positive. Negative pregnancy test in case of a woman of reproductive age. Signature of a document proving informed consent. Hospital admission for SARS-CoV-2 pneumonia. Exclusion Criteria: New alteration of the state of alert that does not revert after interventions 60 minutes after hospital admission. Mean Arterial Pressure (MAP) ≤ 65mmHg despite initial resuscitation on arrival at the centre. History of allergy to chloroquine, hydroxychloroquine, piperaquine or primaquine. Known patient with hearing loss. Received chloroquine or hydroxychloroquine in the last 3 months. Patients with cirrhosis or elevation of aspartate transaminase (AST) or alanine transaminase (ALT) greater than three times the upper normal limit. Patients with calculated glomerular filtration rate by Modification of Diet in Renal Disease study equation (MDRD) < 30ml/min 1.73 m2. Patients known to be deficient in 6-phosphate dehydrogenase Patients known to have retinopathy or macular disease. History of acute myocardial infarction in the last 6 months, unstable angina, ventricular tachycardia, ventricular fibrillation or class III-IV heart failure according to New York Heart Association. Electrocardiogram QTc interval ≥ 480 ms. Patients with hypomagnesemia or uncorrected hypokalemia. Patients with a history of psychiatric illness. Patients who are pregnant or nursing. Patients taking quinolones, dextropropoxyphene, amiodarone, flecainide, cisapride, domperidone, atazanavir or lopinavir. Patients with acute pancreatitis. Patients who the investigators deem unsuitable for participation in the clinical trial.

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: double blind randomized clinical trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Chloroquine<br>Patients will receive chloroquine phosphate 450 mg every 12 hours orally | Drug: Chloroquine Phosphate Tablets<br>* Orally administered<br>* Other names: Losartan tablets;|
| Experimental: Chloroquine plus losartan<br>Patients will receive Chloroquine phosphate 450mg orally every 12hrs plus Losartan 25mg orally every 12hrs | Drug: Chloroquine Phosphate Tablets<br>* Orally administered<br>* Other names: Losartan tablets;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall mortality | Determine all-cause mortality up to 28 days after randomization of Chloroquine Phosphate Compared to Chloroquine Phosphate plus Losartan in Non-Critically Ill Patients with SARS-CoV-2 Pneumonia. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical outcome assessment | Compare the clinical outcome of Chloroquine Phosphate treatment vs Chloroquine Phosphate plus Losartan in the follow-up visit at the end of treatment. Acording to NIH and FDA definitions | 28 days | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Assess the adverse events associated to chloroquine and chloroquine plus losartan at 28 days | 28 days | 
| Time to negative SARS-CoV-2 test | Time to negative Polymerase chain reaction (PCR) test from baseline: testing every 48hrs until a negative result | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, SARS-CoV-2 pneumonia, Chloroquine phosphate, Losartan