Trial NCT04315896
Publication Hernandez-Cardenas C, PloS One, 2021 (published paper)
Dates: 2020-04-08 to 2020-07-12
Funding: Mixed (Participating hospitals; CONACYT (National Council of Science and Technology of Mexico); SANOFI)
Conflict of interest: *
| Methods | |
| RCT Blinding: quadruple blinding | |
| Location :
Multicenter / Mexico Follow-up duration (days): 30 | |
| Inclusion criteria | Adults over 18 years of age, with <14 days from symptoms onset; Confirmed diagnosis of COVID-19 by RT-PCR (in a pharyngeal/nasopharyngeal swab sample or in a tracheal aspirate/bronchial lavage) that required hospitalization as decided by the attending physicians; Hypoxemia (SaO2 <90% ambient air or PaO2/FIO2 <250 in Mexico City); Opacities in the chest roentgenogram or the tomography; Hospitalization was usually due to the requirement of respiratory support, either supplementary oxygen or mechanical ventilation. |
| Exclusion criteria | Known previous COVID-19 infection; Previously treated with HCQ or chloroquine during the last month; Pregnant woman; Planned transfer to another hospital unit; Participating in another COVID-19 trial; Contraindication to start or continue HCQ including known hypersensitivity to HCQ or chloroquine, a corrected QT interval (QTc) >0.50 s, severe liver or kidney disease, a history of pre-existing maculopathy, >11 score points (of a maximum of 21 score points) on a scale assessing the risk of QTc prolongation in hospitalized patients, including age, gender, myocardial infarction or heart failure, sepsis, the use of drugs known to prolong the QTc or diuretics, and hypokalemia. |
| Interventions | |
| Treatment
Hydroxychloroquine 200 mg twice a day for 10 days, orally or by nasogastric tube |
|
| Control
Placebo | |
| Participants | |
| Randomized 214 participants (n1=106 / n2= 108) | |
| Characteristics of participants N=214 Mean age : 49.5 161 males Severity : Mild: n=0 / Moderate: n=0/ Severe: n=52 Critical: n=162 | |
| Primary outcome | |
| In the register All-cause hospital mortality [ Time Frame: From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to 120 days ] | |
| In the report 30-day mortality rate after randomization | |
| Documents available |
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 published article, the pre-print article and the trial registry were used in data extraction and assessment of risk of bias. The statistical analysis plan was not available. There were no substantive differences between the registry and the pre-print/published article in population, procedures or interventions. Outcomes were pre-specified at 120 days vs 30 days in the published report. The study was stopped early due to reduced recruitment following the worldwide suspension of several large trials testing HCQ.
Quote: "In mid-July, 2020, the rhythm of recruitment was reduced drastically, due to several reasons including patient refusal, that of their relatives, or that of their treating physicians, coinciding with the worldwide suspension of several large trials testing HCQ in which no benefits of the drug were found. Thus, it became unfeasible to complete the proposed sample size." The study was updated on the November 24th, 2021 with data from the published report. |