Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19
Barrat-Due et al.
, Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19
, Annals of Internal Medicine, doi:10.7326/M21-0653, NCT04321616
Small RCT in Norway with 52 HCQ and 42 remdesivir patients, showing no significant differences with treatment. Add-on trial to WHO Solidarity. NCT04321616 (history)
risk of death, 120.0% higher, RR 2.20, p = 0.35, treatment 4 of 45 (8.9%), control 2 of 48 (4.2%), adjusted per study.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Barrat-Due et al., 13 Jul 2021, Double Blind Randomized Controlled Trial, Norway, peer-reviewed, 41 authors, average treatment delay 8.0 days, trial NCT04321616 (history)
Abstract: ORIGINAL RESEARCH
Annals of Internal Medicine
Evaluation of the Effects of Remdesivir and Hydroxychloroquine on
Viral Clearance in COVID-19
A Randomized Trial
Andreas Barratt-Due, PhD; Inge Christoffer Olsen, PhD; Katerina Nezvalova-Henriksen, PhD; Trine Kåsine, MD;
Fridtjof Lund-Johansen, PhD; Hedda Hoel, PhD; Aleksander Rygh Holten, PhD; Anders Tveita, PhD; Alexander Mathiessen, PhD;
Mette Haugli, MD; Ragnhild Eiken, MD; Anders Benjamin Kildal, PhD; Åse Berg, PhD; Asgeir Johannessen, PhD;
Lars Heggelund, PhD; Tuva Børresdatter Dahl, PhD; Karoline Hansen Skåra, MSc; Pawel Mielnik, MD; Lan Ai Kieu Le, MD;
Lars Thoresen, MD; Gernot Ernst, MD; Dag Arne Lihaug Hoff, PhD; Hilde Skudal, MD; Bård Reiakvam Kittang, PhD;
Roy Bjørkholt Olsen, PhD; Birgitte Tholin, MD; Carl Magnus Ystrøm, MD; Nina Vibeche Skei, MD; Trung Tran, PhD;
Susanne Dudman, PhD; Jan Terje Andersen, PhD; Raisa Hannula, MD; Olav Dalgard, PhD; Ane-Kristine Finbråten, PhD;
Kristian Tonby, PhD; Bjorn Blomberg, PhD; Saad Aballi, MD; Cathrine Fladeby, PhD; Anne Steffensen, MSc; Fredrik Müller, PhD;
Anne Ma Dyrhol-Riise, PhD; Marius Trøseid, PhD; and Pål Aukrust, PhD; for the NOR-Solidarity trial*
Background: New treatment modalities are urgently needed
for patients with COVID-19. The World Health Organization
(WHO) Solidarity trial showed no effect of remdesivir or hydroxychloroquine (HCQ) on mortality, but the antiviral effects of these
drugs are not known.
Objective: To evaluate the effects of remdesivir and HCQ on
all-cause, in-hospital mortality; the degree of respiratory failure
and inﬂammation; and viral clearance in the oropharynx.
Design: NOR-Solidarity is an independent, add-on, randomized controlled trial to the WHO Solidarity trial that included
biobanking and 3 months of clinical follow-up (ClinicalTrials.
Setting: 23 hospitals in Norway.
Patients: Eligible patients were adults hospitalized with conﬁrmed SARS-CoV-2 infection.
Intervention: Between 28 March and 4 October 2020, a
total of 185 patients were randomly assigned and 181 were
included in the full analysis set. Patients received remdesivir
(n = 42), HCQ (n = 52), or standard of care (SoC) (n = 87).
Measurements: In addition to the primary end point of
WHO Solidarity, study-speciﬁc outcomes were viral clearance
n February 2020, a World Health Organization (WHO)
expert group recommended that 4 drugs approved for
other indications—hydroxychloroquine (HCQ), remdesivir,
ritonavir-boosted lopinavir, and interferon-b 1a—should
be evaluated in an international, adaptive, open-label,
randomized clinical trial and compared with standard of
care (SoC) in the treatment of hospitalized patients with
SARS-CoV-2 infection. This initiative resulted in initiation
of the WHO Solidarity trial (1). The HCQ and lopinavir
groups of this trial were subsequently stopped because of
reported lack of effect based on emerging external evidence from the RECOVERY (Randomised Evaluation of
COVID-19 Therapy) trial, as well as internal evidence from
interim analyses (2).
In October 2020, the WHO Solidarity trial consortium
published interim results, reporting that all of the repurposed drugs evaluated showed little or no effect on inhospital mortality and did not reduce the need for mechanical
in oropharyngeal specimens, the degree of respiratory failure, and inﬂammatory variables.
Results: No signiﬁcant differences were seen between treatment
groups in mortality during hospitalization. There was a..
is less effective
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