Trial NCT04304053
Publication Mitja O, N Engl J Med, 2020
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 criteria1. Asymptomatic individuals exposed to a PCR confirmed COVID19 case within 7 days as either a healthcare worker, a household contact, a nursing home worker or nursing home resident.
2. Aged ≥18 years male or female.
3. In women of childbearing potential, negative pregnancy test and commitment to use contraceptive method throughout the study.
4. Willing to take study medication.
5. Willing to comply with all study procedures.
6. Able to provide oral, informed consent and/or assent.
Exclusion criteria1. With known history of cardiac arrhythmia (or QT prolongation syndrome).
2. Unable to take drugs by mouth.
3. With significantly abnormal liver function (Child Pugh C)
4. Need of dialysis treatment, or GFR≤30 mL/min/1.73 m2.
5. Participants with psoriasis, myasthenia, hematopoietic and retinal diseases, CNS-related hearing loss or glucose-6-phosphate dehydrogenase deficit.
6. Persons already treated with any of the study drugs during the last 30 days.
7. Pregnant or lactating women.
8. 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

Yes. In English

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."
This study was updated on September 21st with data from contact with authors.
This study was updated on December 10th with data from the published manuscript.