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:
Participant gender:
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
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