Publication Rajasingham R
Dates: 4/6/2020 to 5/26/2020
Funding: Mixed (Jan and David Baszucki; Steve Kirsch; Rainwater Charitable Foundation; Alliance of Minnesota Chinese Organizations; Minnesota Chinese Chamber of Commerce; University of Minnesota Foundation)
Conflict of interest: No conflicts of interest
Multicenter / Canada, USA |
Follow-up duration (days): 84
|Inclusion criteria||Healthcare workers aged 18 years and older with ongoing exposure to persons with Covid-19. A high-risk healthcare worker was defined as working in an emergency department or intensive care unit, on a dedicated Covid-19 hospital ward, as a first responder, or whose job description included regularly performing aerosol-generating procedures (e.g., anesthesiologists or otolaryngologists), and included physicians, nurses, advanced practice providers, and other personnel (e.g., respiratory therapists).|
|Exclusion criteria||Persons who reported active or prior Covid-19 (confirmed or symptom-compatible illness), no expected exposure to patients, or contraindication to hydroxychloroquine.
Additional exclusion criteria included, prior allergy or adverse reaction to chloroquine or hydroxychloroquine, known QT prolongation, G6PD deficiency, porphyria, prior retinal eye disease, chronic kidney disease (stage 4, 5, or dialysis), weight <40kg.
Current use of the following medications was contraindicated: hydroxychloroquine, chloroquine, flecainide, amiodarone, digoxin, procainamide, propafenone, artemether, lumefantrine, mefloquine, tamoxifen, or methotrexate.
In Canada, additional exclusions requested by Health Canada were: pregnancy, breastfeeding, severe diarrhea or vomiting, known cirrhosis with history of encephalopathy or ascites, current use of systemic chemotherapy, residing in a remote location not serviced by courier, ventricular arrhythmia, or history of sudden cardiac death, or QT prolonging medicines (dapsone, dofetilide, sotalol, levofloxacin, ciprofloxacin, moxifloxacin, azithromycin, clarithromycin, erythromycin, ketoconazole, itraconazole, amitriptyline, citalopram, desipramine, escitalopram, imipramine, doxepin, fluoxetine, sertraline, bupropion, venlafaxine, haloperidol, droperidol, lithium, quetiapine, thioridazine, ziprasidone, methadone, or current use of sumatriptan or zolmitriptan if not prescribed as needed).
Hydroxychloroquine 400mg QW
Hydroxychloroquine 400mg BW
1483 participants n1=494/ n2=494/ n3=495
|Characteristics of participants|
Mean age : NR
|In the register|
COVID-19-free survival [ Time Frame: up to 12 weeks ]
|In the report|
Covid-19free survival time by laboratory-confirmed or probable compatible illness
|Risk of bias
The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review
In addition to the pre-print article, the study registry and supplementary appendix were used in data extraction and risk of bias assessment. Due to the inability to recruit participants and hence the termination of the trial after the first interim analysis, the target sample size specified in the registry was not achieved.
Quote: "Before the first interim analysis on May 21, 2020, it became apparent that we would not meet our initial enrollment goal of 3150 participants (Supplemental Figure S2). At the first interim analysis, and without unblinding of treatment allocation, the principal investigator proposed to the data safety monitoring board stopping enrollment due to an inability to recruit participants, with continued follow up for those already enrolled. Enrollment was stopped on May 26, 2020, and outcomes data were collected through July 13, 2020."
There were no changes in intervention and control treatments between the trial registration and pre-print article. The primary and secondary outcomes were also consistent between the two sources, except for the registry outcome 'Ordinal scale of COVID-19 disease maximum severity if COVID-29 diagnosed at study end' which was not reported in the pre-print article.