Azithromycin Added to Hydrochloroquine in Patients Admitted to Intensive Care With COVID-19: Randomised Controlled Trial

Summary

Trial design: Prospective, multi-centre, randomised, pragmatic, double blind trial

Methods:

Participants: Adult (\>18 years) within 24 hours of admission to intensive care unit with proven or suspected COVID-19 infection, whether or not mechanically ventilated. Exclusion criteria: symptoms of febrile disease for ≥1 week, treatment limitations in place or moribund patients, allergy or intolerance of any study treatment, incl. long QT syndromes, participation in another outcome-based interventional trial within last 30 days, patients taking Hydrochloroquine for other indication than COVID-19, pregnancy.

Interventions: Patients will be randomised in 1:1:1 ratio to receive Hydrochloroquine 800mg orally in two doses followed by 400mg daily in two doses and Azithromycin 500 mg orally in one dose followed by 250 mg in one dose for a total of 5 days (HC-A group) or Hydrochloroquine+ placebo (HC group) or placebo + placebo (C-group) in addition to best standard of care, which may evolve during the trial period but will not differ between groups.

Objective: To test the hypothesis that early administration of combination therapy slows disease progression and improves mechanical-ventilation free survival.

Outcomes:

Primary outcome: Composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14.

Secondary outcomes:

Composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14 in the subgroup of patients without the need of mechanical ventilation at baseline.

ICU-LOS D28 and D 90 mortality (in hospital)

Tertiary (exploratory) outcomes:

Viral load at D7 of study enrolment (No of viral RNA copies/ml of blood), proportion of patients alive and rtPCR negative from nasal swab at D14, Difference of FiO2 requirement and respiratory system compliance between day 0 and 7.

Randomization: In 1:1:1 ratio and stratified according to study centre and patients age (cut-off 70 years) Blinding (masking): Patients, treating clinicians, outcome assessors and data analyst will be blinded to study treatment allocation. Unblinded study pharmacist or research nurse will prepare investigational products.

Conditions

• COVID-19
• Respiratory Failure

Interventions

DRUG

Azithromycin

orally or into nasogastric tube for 5 days

DRUG

Hydroxychloroquine

orally or into nasogastric tube for 5 days

DRUG

Placebo

orally or into nasogastric tube for 5 days

Sponsors & Collaborators

• Masaryk Hospital Usti nad Labem

  collaborator OTHER

• University Hospital Pilsen

  collaborator OTHER

• The Faculty Hospital Na Bulovce

  collaborator OTHER

• St. Anne's University Hospital Brno, Czech Republic

  collaborator OTHER

• University Hospital, Motol

  collaborator OTHER

• General University Hospital, Prague

  collaborator OTHER

• University Hospital Olomouc

  collaborator OTHER

• Frantisek Duska, MD, PhD

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-05-13

Primary Completion

2020-11-04

Completion

2020-11-04

Countries

• Czechia

Study Locations