Hydroxychloroquine, Azithromycin in the Treatment of Covid-19

NCT ID: NCT04405921

Last Updated: 2020-06-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-31
• Study Completion Date: 2021-03-31

Brief Summary

This study investigates the efficay and tolerance of 5-days course of hydroxychloroquine or hydroxychloroquine and azithromycin of patients with COVID-19 infection. The investigators will undertake a randomized, double-blind, controlled Trial in the region of Sousse Tunisia

Detailed Description

There is a critical need to identify effective treatments and a number of molecules have been suggested, but The investigators still do not have enough evidence about their efficacy, to treat COVID-19 pneumonia.

One of the most tested treatments was the use of Chloroquine or Hydroxychloroquine associated or not to azithromycin.

Studies have indicated that chloroquine (CQ) shows antagonism against COVID-19 in vitro. It's known to block virus infection by increasing endosomal pH required for virus/cell fusion, as well as interfering with the glycosylation of cellular receptors of SARS-CoV. It's also demonstrated that CQ functioned at both entry, and at postentry stages of the 2019-nCoV infection in Vero E6 cells. Besides its antiviral activity, CQ has an immune-modulating activity, which may synergistically enhance its antiviral effect in vivo.

However, evidence regarding its effects in patients is limited. Among patients with COVID-19, the use of Hydroxychloroquine (HCQ) could significantly shorten time to clinical recovery (TTCR) and promote the absorption of pneumonia. This result has been presented in a randomized controlled trial using two arms HCQ versus conventional treatment. The beneficial effect of HCQ has been proven among mild severity COVID-19 pneumonia but the sample size of this study was limited to 31 patients in each group.

Gautret et al also reported that HCQ treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin. A study showed that azithromycin concentration in phagocytic cells is 40× to 150× higher than plasma concentrations. However, Gautret study has many limitations including selection biases because of non-randomization, a small sample size, and dropout of six patients from the study.

In terms of treatment duration, there is no study supporting a long course treatment of 10 days versus a short course treatment of 5 days for HCQ. This treatment is known to have a large distribution volume of 73 l/kg and a plasma half life going from 22 days to 123 days. This suggests that a short course treatment of Hydroxychloroquine and/or azithromycin could be as effective as a long course treatment.

On the other hand, there are currently no effective specific antivirals or drug combinations supported by high-level evidence, and The investigators don't know if HCQ could be effective or if it's effectiveness may be improved if it's associated with Azithromycin. In fact, this association can lead to improve pneumonia but can also increase the risk of treatment side effects.

Conditions

SARS-CoV-2 Pneumonia; COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Hydroxychloroquine associated to azithromycin

Hydroxychloroquine: 200 mg twice a day orally or via gastric tube (total 400 mg/day) for 5 days. Azithromycin: 500 mg at day 1 then 250 mg/day for 4 days. with standard of care in association to treatments.

Group Type: EXPERIMENTAL

Hydroxychloroquine 200 Mg Oral Tablet

Intervention Type: DRUG

orally or via gastric tube

Azithromycin 250 MG

Intervention Type: DRUG

orally or via gastric tube

Hydroxychloroquine with placebo

Hydroxychloroquine: 200 mg twice a day orally or via gastric tube (total 400 mg/day) for 5 days. with standard of care in association to treatments.

Group Type: ACTIVE_COMPARATOR

Hydroxychloroquine 200 Mg Oral Tablet

Intervention Type: DRUG

orally or via gastric tube

Interventions

Hydroxychloroquine 200 Mg Oral Tablet

orally or via gastric tube

Intervention Type: DRUG

Azithromycin 250 MG

orally or via gastric tube

Intervention Type: DRUG

Other Intervention Names

Plaquenil; Azro 250

Eligibility Criteria

Inclusion Criteria

• PositiveSARS-COV-2 RT-PCR in hospitalized patients in University Hospital Farhat Hached in Sousse Tunisia.
• Had either not received hydroxychloroquine before or had received hydroxychloroquine for at least 1 day and could tolerate a dose of 200 mg of hydroxychloroquine/day.

Exclusion Criteria

• Unableto take oral medication, pregnancy or breast feeding, immune-compromised patients,
• Contraindicationto the studied medications

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hôpital Universitaire Farhat Hached

OTHER

Sponsor Role: lead

Responsible Party

Amel Letaief

Professor of infectious diseases

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University Hospital Farhat Hached

Sousse, , Tunisia

Countries

Tunisia

Central Contacts

Amel Letaief, Professor

Role: CONTACT

ameletaief@gmail.com

21673102501

Facility Contacts

Amel Letaief, Professor

Role: primary

Other Identifiers

PACTT

Identifier Type: -

Identifier Source: org_study_id