Covid-19 Living Data

Trial NCT04304053
Publication Mitja O
Dates: 3/17/2020 to 4/28/2020
Funding: Mixed (Crowdfunding campaign YoMeCorono; Laboratorios Rubió, Laboratorios Gebro Pharma; Zurich Seguros; SYNLAB Barcelona; Generalitat de Catalunya)
Conflict of interest: No conflicts of interest

Methods
	RCT
	Location : Multicenter / Spain Follow-up duration (days): 28
Inclusion criteria	We included adult individuals ? 18 years of age with a recent history of close contact exposure to a PCR confirmed Covid-19 case (i.e., > 15 minutes within two meters, up to seven days before enrolment) and absence of Covid-19-like symptoms on the two weeks preceding enrolment, as either a healthcare worker,a household contact, a nursing home worker or a nursing home resident.In women of childbearing potential, negative pregnancy test and commitment to use contraceptive method throughout the study. Participants willing to take study medication, to comply with all study procedures and able to provide oral, informed consent and/or assent.
Exclusion criteria	Contacts with Covid-19-like signs and symptoms at the time of the baseline visit were considered unpreventable Covid-19 events and were not enrolled in the study. Additional criteria from trial registry: Exclusion Criteria for a contact: With known history of cardiac arrhythmia (or QT prolongation syndrome); Unable to take drugs by mouth; With significantly abnormal liver function (Child Pugh C); Need of dialysis treatment, or GFR?30 mL/min/1.73 m2; Participants with psoriasis, myasthenia, haematopoietic and retinal diseases,CNS-related hearing loss or glucose-6-phosphate dehydrogenase deficit; Persons already treated with any of the study drugs during the last 30 days; Pregnant or lactating women; Any contraindications as per the Data Sheet of Hydroxychloroquine.
Interventions
	Treatment Hydroxychloroquine (*) Duration : 7 days
	Control Standard care Definition of Standard care: * Duration : NA
Participants
	Randomized 2525 participants (n₁=1225 / n₂= 1300)
	Characteristics of participants N=2525 Mean age : 48.7 626 males Severity : Mild: n=* / Moderate: n=/ Severe: n= Critical: n=*
Primary outcome
	In the register 1. Clinical and virological outcome in exposed contacts [Time Frame: Up to 14 days after start of treatment] Incidence of secondary PCR confirmed symptomatic Covid-19 episodes among contacts after high risk PCR+ exposure; and 2. Transmission of SARS-CoV-2 in exposed contacts [Time Frame: Up to 14 days after start of treatment] Incidence of symptomatically compatible or a PCR-positive result regardless of symptoms
	In the report onset of a confirmed Covid-19 episode, defined as symptomatic illness (at least one of the following symptoms: fever, cough, difficulty breathing, myalgia, headache, sore throat, new olfactory and taste disorder(s), or diarrhea) and a positive SARS-CoV-2 RT-PCR test.
Documents avalaible	Protocol NR Statistical plan NR Data-sharing stated 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 report, the registry was used to extract data. This study uses the number of randomized participants as "Safety sample" for the analysis of "Adverse events" and "Serious adverse events". There was a large number of randomized participants excluded from the analysis. The 2525 randomised contacts were from 672 index cases (clusters). Comment on clusters: median (IQR) size of clusters was 2 (1.0, 3.0) in both groups. The sample size estimation initially used an intraclass correlation of 1.0 but then the sample size estimation was subsequently revised. Some outcomes were reported accounting for clustering while others were simply raw numbers. Quote on methods: "The cumulative incidence in primary, secondary, and safety outcomes was compared at the individual level using a binomial regression model with robust sandwich standard errors to account for clustering within rings. We defined a generalized linear model with a binomial distribution and a logarithm link function to estimate the relative risk (RR) as a measure of effect. The individual-level variables we adjusted for are age, gender, region, and time of exposure."