Hydroxychloroquine, Azithromycin in the Treatment of Covid-19 (PACTT)

Hydroxychloroquine, Azithromycin in the Treatment of Covid-19 Pneumonia: A Randomized,Open-label,Controlled Clinical Trial

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

Study Overview

• Status: Unknown
• Conditions: COVID-19; SARS-CoV-2 Pneumonia
• Intervention / Treatment: Drug: Hydroxychloroquine 200 Mg Oral Tablet; Drug: Azithromycin 250 MG

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.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Amel Letaief, Professor; Phone Number: 21673102501; Email: ameletaief@gmail.com

Study Locations

• Tunisia
  • Sousse, Tunisia, 4000
    • University Hospital Farhat Hached
    • Contact: Amel Letaief, Professor

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:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Hydroxychloroquine 200 Mg Oral Tablet; orally or via gastric tube; Other Names: Plaquenil; Drug: Azithromycin 250 MG; orally or via gastric tube; Other Names: Azro 250
Active Comparator: 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.	Drug: Hydroxychloroquine 200 Mg Oral Tablet; orally or via gastric tube; Other Names: Plaquenil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical recovery at day-14, from the start of treatment.	Clinical recovery is defined as a complete resolution clinical signs appeared during the medical history and related to COVID-19.	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viral Clearance via RT-PCR at day 5- 7-10 and day 14	RT-PCR will be realized in same laboratory	5- 7-10 and day 14

Collaborators and Investigators

• Sponsor: Centre Hôpital Universitaire Farhat Hached

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2020
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): March 1, 2021

Study Registration Dates

• First Submitted: May 26, 2020
• First Submitted That Met QC Criteria: May 26, 2020
• First Posted (Actual): May 28, 2020

Study Record Updates

• Last Update Posted (Actual): June 19, 2020
• Last Update Submitted That Met QC Criteria: June 18, 2020
• Last Verified: June 1, 2020

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; Lung Diseases; COVID-19; Pneumonia; 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: PACTT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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