Trial NCT04322396, EudraCT 2020-001198-55
Publication Sivapalan P, Eur Respir J, 2021 (published paper)
Dates: 2020-04-06 to 2020-12-21
Funding: Mixed (The Novo Nordisk Foundation, Herlev and Gentofte Hospital, University Hospital of Copenhagen.)
Conflict of interest: Yes

Methods
RCT
Blinding: quadruple blinding
Location : Multicenter / Denmark
Follow-up duration (days): 30
Inclusion criteriaAt least 18 years of age; admitted to hospital with a confirmed positive test for SARS-CoV-2 infection by RT-PCR; hospitalised for ≤ 48 h; signed informed consent to participate
Exclusion criteriaReceived > 5 L oxygen supply; known intolerance/allergy to the study drugs; neurogenic hearing loss; psoriasis; retinopathy; maculopathy; visual field changes; breastfeeding/pregnant; severe liver disease (international normalised ratio > 1.5 spontaneously); severe gastrointestinal disease (investigator-assessed liver disease, severe ulcerative colitis or Crohn's disease, peptic ulcer disease, or cancer); neurological or haematological disorder; estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2; clinically significant cardiac conduction disorder/arrhythmia or a prolonged corrected QT interval (QTc; i.e., F > 480 ms for males or > 470 ms for females); myasthenia gravis; receiving treatment with digoxin; glucose-6-phosphate dehydrogenase deficiency; porphyria; hypoglycaemia (blood glucose < 3.0 mmol/L); unable to give informed consent; severe linguistic problems that significantly hindered cooperation; receiving treatment with ergot alkaloids
Interventions
Treatment
Hydroxychloroquine + Azithromycin
HCQ: 200 mg orally twice a day for 15 days. AZM: 500 mg orally once a day for 3 days, then 250 mg orally once a day for 12 days.
Control
Placebo
Participants
Randomized
117 participants (n1=61 / n2= 56)
Characteristics of participants
N=117
Mean age : NR
65 males
Severity : Mild: n=* / Moderate: n=*/ Severe: n=27 Critical: n=0
Primary outcome
In the register
Days alive and discharged from hospital within 14 days
In the report
Days alive and out of hospital (DAOH) within 14 days from randomisation.
Documents
available

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing stated
Risk of bias
Overall
The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review
Low
General comment In addition to the published article, the full and published study protocols and statistical analysis plan, prospective trial registries ( NCT04322396), EudraCT 2020-03-21) and supplementary appendices were used in data extraction and assessment of risk of bias. There were no substantive differences between the published article and the protocols or registries in population, procedures, interventions or outcomes. The registry and protocol primary outcome reflects the reported primary outcome. Recruitment was terminated at the first planned interim analysis after a recommendation from the data monitoring board based on pre-specified futility criteria, and therefore the study did not achieve its pre-specified target sample size.