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

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

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

Study Overview

• Status: Withdrawn
• Conditions: COVID-19 Pneumonia
• Intervention / Treatment: Drug: Chloroquine Phosphate Tablets

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Mexico
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
      • Hospital Universitario José E. Gonzalez

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men or women ≥18 years.
2. Oral tolerance or access for enteral administration of medication.
3. PCR or IgM for SARS-CoV-2 positive.
4. Negative pregnancy test in case of a woman of reproductive age.
5. Signature of a document proving informed consent.
6. Hospital admission for SARS-CoV-2 pneumonia.

Exclusion Criteria:

1. New alteration of the state of alert that does not revert after interventions 60 minutes after hospital admission.
2. Mean Arterial Pressure (MAP) ≤ 65mmHg despite initial resuscitation on arrival at the centre.
3. History of allergy to chloroquine, hydroxychloroquine, piperaquine or primaquine.
4. Known patient with hearing loss.
5. Received chloroquine or hydroxychloroquine in the last 3 months.
6. Patients with cirrhosis or elevation of aspartate transaminase (AST) or alanine transaminase (ALT) greater than three times the upper normal limit.
7. Patients with calculated glomerular filtration rate by Modification of Diet in Renal Disease study equation (MDRD) < 30ml/min 1.73 m2.
8. Patients known to be deficient in 6-phosphate dehydrogenase
9. Patients known to have retinopathy or macular disease.
10. 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.
11. Electrocardiogram QTc interval ≥ 480 ms.
12. Patients with hypomagnesemia or uncorrected hypokalemia.
13. Patients with a history of psychiatric illness.
14. Patients who are pregnant or nursing.
15. Patients taking quinolones, dextropropoxyphene, amiodarone, flecainide, cisapride, domperidone, atazanavir or lopinavir.
16. Patients with acute pancreatitis.
17. Patients who the investigators deem unsuitable for participation in the clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Chloroquine; Patients will receive chloroquine phosphate 450 mg every 12 hours orally	Drug: Chloroquine Phosphate Tablets; Orally administered; Other Names: Losartan tablets
EXPERIMENTAL: Chloroquine plus losartan; Patients will receive Chloroquine phosphate 450mg orally every 12hrs plus Losartan 25mg orally every 12hrs	Drug: Chloroquine Phosphate Tablets; Orally administered; Other Names: Losartan tablets

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hospital Universitario Dr. Jose E. Gonzalez
• Investigators: Principal Investigator: Adrian Camacho Ortiz, MD, Hospital Universitario "Dr. Jose Eleuterio Gonzalez", UANL

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 10, 2020
• Primary Completion (ACTUAL): June 10, 2020
• Study Completion (ACTUAL): February 16, 2021

Study Registration Dates

• First Submitted: April 26, 2020
• First Submitted That Met QC Criteria: June 10, 2020
• First Posted (ACTUAL): June 11, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 18, 2021
• Last Update Submitted That Met QC Criteria: February 16, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: COVID-19; Losartan; SARS-CoV-2 pneumonia; Chloroquine phosphate
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; COVID-19; Pneumonia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Anti-Infective Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Antimalarials; Amebicides; Filaricides; Antinematodal Agents; Anthelmintics; Chloroquine; Chloroquine diphosphate; Losartan
• Other Study ID Numbers: IF20-00003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No