Hidroxicloroquina With Azitromicina Versus Hidroxicloroquina and Placebo Int Patients With Mild COVID-19 (Omehecatl)

Double-blind, Randomized, Prospective, Parallel Study to Demonstrate the Efficacy and Safety of Outpatient Treatment of the Fixed Combination of Hydroxychloroquine With Azithromycin Versus Hydroxychloroquine Treatment and Placebo Treatment in Patients Diagnosed With Mild COVID-19 Infection

Chloroquine and hydroxychloroquine are two antimalarial drugs that are also used in autoimmune diseases. Chloroquine analogs have been shown to inhibit endosome acidification and exhibit nonspecific antiviral activity at high micromolar concentration in vitro against a wide range of emerging viruses (HIV, dengue, hepatitis C, chikungunya, influenza, Ebola, SARS, and MERS ). virus) and more recently COVID-19. On the other hand, azithromycin is a macrolide antibiotic indicated for infections caused by sensitive pathogens, but which in combination with Hydroxychloroquine has shown a synergistic effect against the SARS-CoV-2 virus.

International studies show the lack of beneficial effect in hospitalized or mechanically ventilated patients. Referring that because these medications reduce the in case of having a beneficial effect it would be in the early onset, to avoid inflammation (cytokine storm), and thus prevent hospitalizations.

The present study focuses on characterizing the possible synergy of the fixed combination of hydroxychloroquine associated with azithromycin in the treatment of Covid-19 from mild to moderate manifestations. Three treatment schemes are proposed with a 10-day follow-up, a) the fixed combination of Hydroxychloroquine / Azithromycin (combination of interest), b) Hydroxychloroquine (active comparison group) and c) non-active control group, using placebo. A group of patients between 18 and 75 years old is considered, who may or may not present other comorbidities. Follow-up will be carried out through quantification of viral load, evaluation of the systemic inflammatory state, changes in clinical manifestations and possible effect on the reduction of hospitalizations. Therefore, it is proposed to carry out the following project.

objective To determine the efficacy and safety of Hydroxychloroquine / Azithromycin fixed combination compared to Hydroxychloroquine or placebo in outpatients with Research design: Phase II, multicenter, prospective, randomized, parallel, longitudinal, double-blind study.

Medications to use Group 1. Fixed combination of Hydroxychloroquine with Azithromycin 200 mg / 250 mg one tablet every 12 hours for five days and continue with Hydroxychloroquine 200 mg one tablet every 12 hours for 5 more days.

Group 2. Hydroxychloroquine 200 mg, one tablet every 12 hours for ten days. Group 3. Placebo one tablet every 12 hours for ten days.

Study Overview

• Status: Recruiting
• Conditions: Covid19
• Intervention / Treatment: Drug: Hydroxychloroquine with Azithromycin

• Study Type: Interventional
• Enrollment (Anticipated): 105
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Mexico
  • Mexico City
    • Benito Juárez, Mexico City, Mexico, 03100
      • Recruiting
      • UMF 28
      • Contact: Ivonne A Roy, MD; Phone Number: 525522704760; Email: ivonne3316@gmail.com
      • Sub-Investigator: Magaly A Ortiz Zamora, MD
      • Sub-Investigator: Lourdes G Navarro Susano, MD
      • Principal Investigator: Ivonne A Roy García, MD
    • Cuauhtémoc, Mexico City, Mexico, 06600
      • Not yet recruiting
      • Fundación IMSS
      • Contact: Martha M Zapata Tarrés, MD; Phone Number: 5554184099
      • Sub-Investigator: Marta M Zapata Tarrés, MD
      • Principal Investigator: Pedro Gutierrez Castrellón, MD
      • Sub-Investigator: Romeo Rodríguez Suárez, MD
  • State Of Mexico
    • Cuautitlán Izcalli, State Of Mexico, Mexico, 54720
      • Recruiting
      • UMF 52
      • Contact: Moises Moreno, MD; Phone Number: 5565593877; Email: sesby14@gmail.com
      • Sub-Investigator: Miroslava Guzmán Rivas, MD
      • Principal Investigator: Moises Moreno Noguez, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have given the signed informed consent form.
• Confirmed diagnosis of COVID-19 infection by PCR with mild symptoms.
• Patients who attend the primary care respiratory care module in the participating units and who have symptoms suggestive of COVID-19, who comply with the current operational definition.
• With or without comorbidities such as hypertension, controlled diabetes mellitus, cardiovascular or respiratory diseases.
• Controlled diabetes will be considered to be that which is evidenced by results of glycosylated hemoglobin less than 7% in the last 3 tables, whether it is reported in your beneficiary file or by external laboratory results.
• Electrocardiogram (ECG) normal or with variations without clinical relevance, with QT interval <450 ms.
• No contraindication to study drugs (history of hypersensitivity to study drugs, including macrolides, patients with renal failure (eGFR <40 mL / min) or on renal replacement therapy, patients with a history of retinopathy or macular degeneration.

Exclusion Criteria:

• Patients who are participating in studies with investigational drugs.
• Pregnancy or breastfeeding.
• Type 1 diabetes
• % Type II diabetes mellitus with glycated hemoglobin greater than 7%.
• Patients requiring hospitalization or assisted mechanical ventilation
• Cardiac disorders with cardiac conduction delay (QT segment ≥ 450 ms

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hydroxychloroquine with Azithromycin; Fixed combination of Hydroxychloroquine with Azithromycin 200 mg / 250 mg one tablet every 12 hours for five days and continue with Hydroxychloroquine 200 mg one tablet every 12 hours for 5 more days.	Drug: Hydroxychloroquine with Azithromycin; Fixed combination of Hydroxychloroquine with Azithromycin 200 mg / 250 mg one tablet every 12 hours for five days and continue with Hydroxychloroquine 200 mg one tablet every 12 hours for 5 more days.; Other Names: Azithromycin
Active Comparator: Hydroxychloroquine; Hydroxychloroquine 200 mg, one tablet every 12 hours for ten days.	Drug: Hydroxychloroquine with Azithromycin; Fixed combination of Hydroxychloroquine with Azithromycin 200 mg / 250 mg one tablet every 12 hours for five days and continue with Hydroxychloroquine 200 mg one tablet every 12 hours for 5 more days.; Other Names: Azithromycin
Placebo Comparator: Placebo; Placebo one tablet every 12 hours for ten days.	Drug: Hydroxychloroquine with Azithromycin; Fixed combination of Hydroxychloroquine with Azithromycin 200 mg / 250 mg one tablet every 12 hours for five days and continue with Hydroxychloroquine 200 mg one tablet every 12 hours for 5 more days.; Other Names: Azithromycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalization	Being admitted for hospitalization	15 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viral load	Measured by RT-PCR	0 and 14 days
Clinical safety	any adverse event	21 days

Collaborators and Investigators

• Sponsor: Coordinación de Investigación en Salud, Mexico
• Collaborators: Ultra Laboratorios SA. de CV.

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2021
• Primary Completion (Anticipated): August 1, 2021
• Study Completion (Anticipated): August 1, 2021

Study Registration Dates

• First Submitted: June 25, 2021
• First Submitted That Met QC Criteria: July 14, 2021
• First Posted (Actual): July 16, 2021

Study Record Updates

• Last Update Posted (Actual): August 4, 2021
• Last Update Submitted That Met QC Criteria: August 3, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Azithromycin; Hydroxychloroquine
• Other Study ID Numbers: 2020-785-138

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Database with all non identifiable data will be available upon request.
• IPD Sharing Time Frame: 6 months
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No