Trial NCT04354428
Publication Johnston C, 2021 (published paper)
Dates: 4/15/2020 to 7/27/2020
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: double blinding | |
| 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 â¥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 1 Hydroxychloroquine+Azithromycin | |
| Control Vitamin C+Placebo | |
| Control Hydroxychloroquine+Placebo | |
| Participants | |
| Randomized 231 participants n1=77/ n2=83/ n3=71 | |
| Characteristics of participants N=231 Mean age : NR 100 males Severity : Mild: n=0 / Moderate: n=0/ Severe: n=0 Critical: n=0 | |
| 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 stated NR |
| 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. |