Hydroxychloroquine, Azithromycin in the Treatment of Covid-19

COVID-19 Clinical Trial

— PACTT  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04405921
• Other study ID #: PACTT
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: July 2020
• Est. completion date: March 2021

Study information

• Verified date: June 2020
• Source: Centre Hôpital Universitaire Farhat Hached
• Contact: Amel Letaief, Professor
• Phone: 21673102501
• Email: ameletaief[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: March 2021
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Pneumonia
• SARS-CoV-2 Pneumonia

Intervention

Drug:
• Hydroxychloroquine 200 Mg Oral Tablet
orally or via gastric tube
• Azithromycin 250 MG
orally or via gastric tube

Locations

Country	Name	City	State
Tunisia	University Hospital Farhat Hached	Sousse

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hôpital Universitaire Farhat Hached

Country where clinical trial is conducted

Tunisia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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