Assessing the efficacy and safety of hydroxychloroquine as outpatient treatment of COVID-19: a randomized controlled trial
Schwartz et al.,
Assessing the efficacy and safety of hydroxychloroquine as outpatient treatment of COVID-19: a randomized..,
CMAJ Open, doi:10.9778/cmajo.20210069
Small early terminated late treatment RCT not showing significant differences. The HCQ group was a median of 7 days from symptom onset at baseline, which may not include the delay delivering the medication. From the 4 HCQ hospitalizations, only one is in the per-protocol analysis, and that patient was hospitalized one day after randomization (authors do not specify if the patient received and took any HCQ before the hospitalization). The trial was terminated early due to the fraudulent Lancet article (wording here is notably different between the submitted and published versions). Per-protocol analysis, the submitted version, and the peer-review comments (two reviewers, only one with substantial feedback) are in the supplementary material.
risk of ICU admission, 133.3% higher, RR 2.33, p = 1.00, treatment 1 of 111 (0.9%), control 0 of 37 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm).
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risk of hospitalization, 533.3% higher, RR 6.33, p = 0.57, treatment 4 of 111 (3.6%), control 0 of 37 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm).
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risk of ICU admission, 141.9% higher, RR 2.42, p = 1.00, treatment 1 of 74 (1.4%), control 0 of 31 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm), per-protocol.
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risk of hospitalization, 141.9% higher, RR 2.42, p = 1.00, treatment 1 of 74 (1.4%), control 0 of 31 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm), per-protocol.
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Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
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Schwartz et al., 18 Jun 2021, Double Blind Randomized Controlled Trial, Canada, peer-reviewed, 20 authors, average treatment delay 7.0 days, dosage 800mg day 1, 400mg days 2-5.
Abstract: Research
Assessing the efficacy and safety of hydroxychloroquine
as outpatient treatment of COVID-19: a randomized
controlled trial
Ilan Schwartz MD PhD, Mari E. Boesen MSc, Graziela Cerchiaro PhD, Craig Doram BSc PEng,
Brett D. Edwards MD, Aravind Ganesh MD, Jamie Greenfield MPH, Scott Jamieson BScPT MPH,
Vikram Karnik MD, Carol Kenney RN, Rachel Lim MD, Bijoy K. Menon MD, Kwadwo Mponponsuo MD,
Sarah Rathwell MSc, Karla J. Ryckborst RN, Breanne Stewart RN, Maryna Yaskina PhD, Luanne Metz MD,
Lawrence Richer MD, Michael D. Hill MD MSc; for the ALBERTA HOPE COVID-19 Collaborators
Abstract
Background: Identification of therapies to prevent severe COVID-19 remains a priority. We sought to determine whether hydroxychloroquine treatment for outpatients with SARS-CoV-2 infection could prevent hospitalization, mechanical ventilation or death.
Methods: This randomized controlled trial was conducted in Alberta during the first wave of the COVID-19 pandemic without direct
contact with participants. Community-dwelling individuals with confirmed SARS-CoV-2 infection (by reverse transcription polymerase
chain reaction [RT-PCR] viral ribonucleic acid test) within the previous 4 days, and symptom onset within the previous 12 days, were
randomly assigned to oral hydroxychloroquine or matching placebo for 5 days. Enrolment began Apr. 15, 2020. The primary outcome was the composite of hospitalization, invasive mechanical ventilation or death within 30 days. Secondary outcomes included
symptom duration and disposition at 30 days. Safety outcomes, such as serious adverse events and mortality, were also ascertained.
Outcomes were determined by telephone follow-up and administrative data.
Results: Among 4919 individuals with a positive RT-PCR test, 148 (10.2% of a planned 1446 patients) were randomly assigned,
111 to hydroxychloroquine and 37 to placebo. Of the 148 participants, 24 (16.2%) did not start the study drug. Four participants in
the hydroxychloroquine group met the primary outcome (4 hospitalizations, 0 mechanical ventilation, 4 survived to 30 days) and
none in the placebo group. Hydroxychloroquine did not reduce symptom duration (hazard ratio 0.77, 95% confidence interval 0.49–
1.21). Recruitment was paused on May 22, 2020, when a since-retracted publication raised concerns about the safety of hydroxychloroquine for hospitalized patients with COVID-19. Although we had not identified concerns in a safety review, enrolment was
slower than expected among those eligible for the study, and cases within the community were decreasing. Recruitment goals were
deemed to be unattainable and the trial was not resumed, resulting in a study underpowered to assess the effect of treatment with
hydroxychloroquine and safety.
Interpretation: There was no evidence that hydroxychloroquine reduced symptom duration or prevented severe outcomes
among outpatients with proven COVID-19, but the early termination of our study meant that it was underpowered. Trial registration:
ClinicalTrials.gov, no. NCT04329611
E
ighteen years ago, the severe acute respiratory syndrome (SARS) experience 1–5 highlighted limited
knowledge of early treatments for novel pandemic
respiratory viruses. With the emergence of SARS-CoV-2,
early experience in Wuhan,6 the Lombardy region of Italy7,8
and New York City9 demonstrated the need to suppress
severe disease to prevent health system collapse. Hydroxychloroquine, derived from the centuries-old antimalarial
medicine quinine, has broad..
Late treatment
is less effective
Please send us corrections, updates, or comments. Vaccines and
treatments are complementary. All practical, effective, and safe means should
be used based on risk/benefit analysis. No treatment, vaccine, or intervention
is 100% available and effective for all current and future variants. We do not
provide medical advice. Before taking any medication, consult a qualified
physician who can provide personalized advice and details of risks and
benefits based on your medical history and situation.
FLCCC and
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provide treatment protocols.
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