Trial NCT04328467
Publication Rajasingham R, medRxiv, 2020
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
| Methods | |
| RCT | |
| Location :
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.
Supplementary Appendix: 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). |
| Interventions | |
| Treatment 1 Hydroxychloroquine 400mg QW | |
| Control Placebo | |
| Treatment 3 Hydroxychloroquine 400mg BW | |
| Participants | |
| Randomized 1483 participants n1=494/ n2=494/ n3=495 | |
| Characteristics of participants N=1483 Mean age : NR 691 males | |
| Primary outcome | |
| In the register COVID-19-free survival [ Time Frame: up to 12 weeks ] | |
| In the report | |
| Documents available |
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 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: |