Covid-19 Living Data

Trial NCT04354428
Publication Johnston C, EClinicalMedicine (2021) (published paper)
Dates: 2020-04-15 to 2020-07-27
Funding: Public/non profit (Bill & Melinda Gates Foundation; University of Washington Institute of Translational Health Science (ITHS) grant support from NCATS/NIH funded REDCap)
Conflict of interest: Yes

Methods
	RCT Blinding: Participants, outcome assessor and health care pro
	Location : Multicenter / USA Follow-up duration (days): 28
Inclusion criteria	Age between 18 and 80 years old Laboratory-confirmed SARS-CoV-2 infection diagnosis within the prior 72 h Able to provide informed consent in English or Spanish and to participate in telehealth visits Pregnant and lactating persons were eligible. High-risk cohort enrolled participants with established risk factors for severe COVID-19 including age 60 years or greater Pulmonary disease Diabetes mellitus, Hypertension Self-reported body mass index ≥30 kg/m2. Persons who did not meet any of these criteria were enrolled into the low-risk cohort.
Exclusion criteria	Cirrhosis Stage IV kidney disease, coronary artery disease Certain medications that were associated with torsades de pointes or interacted with study medications (Detailed in Protocol Section 7.9.1).
Interventions
	Treatment HCQ+Placebo HCQ: Initial dose: 400 mg orally twice daily on Day 1. Maintenance dose: 200 mg orally twice daily for 9 days. Placebo (folic acid) Initial dose: 800 mcg orally once daily on Day 1. Maintenance dose: 400 mcg orally once daily for 4 days. HCQ+AZM HCQ: Initial dose: 400 mg orally twice daily on Day 1. Maintenance dose: 200 mg orally twice daily for 9 days. AZM: Initial dose: 500 mg orally once daily on Day 1. Maintenance dose: 250 mg orally once daily for 4 days.
	Control Vitamin C+Placebo Vitamin C: Initial dose: 500 mg orally twice daily on Day 1. Maintenance dose: 250 mg orally twice daily for 9 days. Placebo (folic acid) Initial dose: 800 mcg orally once daily on Day 1. Maintenance dose: 400 mcg orally once daily for 4 days.
Participants
	Randomized participants : Vitamin C+Placebo=83 HCQ+Placebo=71 HCQ+AZM=77
	Characteristics of participants N= 231 Mean age : NR 100 males Severity : Mild: n= 212/ Asymptomatic: n=19 Number of vaccinated participants: NR
Primary outcome
	In the register Lower respiratory tract infection (LRTI) rates [ Time Frame: 28 days from enrolment ] Resting blood oxygen saturation (SpO2<93%) level sustained for 2 readings 2 hours apart and presence of subjective dyspnea or cough Incidence of hospitalization or mortality [ Time Frame: Day 28 after enrolment ] Cumulative incidence of hospitalization or mortality Change in upper respiratory viral shedding [ Time Frame: Day 1 through Day 14 after enrolment ] Time to clearance of nasal SARS-CoV-2, defined as 2 consecutive negative swabs
	In the report Development of LRTI, defined by SpO2<93% on two readings ≥two hours but
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: Yes
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	Some concerns
General comment	In addition to the published article, the study registry, protocol, and statistical analysis plan were used in data extraction and risk of bias assessment. The article reports two treatment arms plus a control arm of a platform study assessing several treatments. Due to the low rate of clinical outcomes, the study was terminated for operational futility. As a result, the target sample size specified in the registry was not achieved. As the medication had a distinctive taste, to maintain participant blinding, all members of a household were randomized to the same treatment group. There is no change from the trial registration in the intervention and control treatments.