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

• Status: Terminated
• Trial end date: 2020-11-04
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Frantisek Duska; Frantisek Duska, MD, PhD
• Collaborators: General University Hospital, Prague; Masaryk Hospital Usti nad Labem; St. Anne's University Hospital Brno, Czech Republic; The Faculty Hospital Na Bulovce; University Hospital Olomouc; University Hospital Pilsen; University Hospital, Motol
• Treatments: Azithromycin; Hydroxychloroquine

Criteria

Inclusion Criteria:

• Adult (>18 years) within 24 hours of admission to intensive care unit with proven or suspected COVID-19 infection. For the purpose of this study, intensive care unit is defined as a facility that allow continuous monitoring of vital functions and oxygen administration . It is expected that most patients will have rtPCR test known within 24 hours of admission to hospital. Nonetheless, if this is not the case (eg. due to overloaded lab facility, lack of supplies) it is possible to randomise a patient based on a strong clinical suspicion of SARS-Cov-2 infection. In case COVID-19 is not confirmed in retrospect, experimental therapy is withdrawn and the study subject is withdrawn from "per protocol" analysis of the primary and secondary outcomes, but remains in "intention-to-treat" cohort for the analysis of safety.

Exclusion Criteria:

• symptoms of febrile disease for ≥1 week, pregnancy, treatment limitations in place or moribund patients, allergy or intolerance of any study treatment, incl. long QT syndromes, myasthenia gravis, allergies or known deficiency of glucose-6-phosphate dehydrogenase, participation in another outcome-based interventional trial within last 30 days, patients taking Hydrochloroquine for other indication than COVID-19.