Peginterferon lambda for the treatment of outpatients with COVID-19: a phase 2, placebo-controlled randomised trial.
Ambulatory Care
/ methods
Antiviral Agents
/ administration & dosage
COVID-19
/ diagnosis
Double-Blind Method
Drug Monitoring
/ methods
Female
Humans
Intention to Treat Analysis
Interleukins
/ administration & dosage
Male
Middle Aged
Polyethylene Glycols
/ administration & dosage
RNA, Viral
/ isolation & purification
SARS-CoV-2
/ isolation & purification
Severity of Illness Index
Treatment Outcome
Viral Load
/ drug effects
Virus Shedding
/ drug effects
COVID-19 Drug Treatment
Journal
The Lancet. Respiratory medicine
ISSN: 2213-2619
Titre abrégé: Lancet Respir Med
Pays: England
ID NLM: 101605555
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
27
10
2020
revised:
03
12
2020
accepted:
04
12
2020
pubmed:
9
2
2021
medline:
14
5
2021
entrez:
8
2
2021
Statut:
ppublish
Résumé
To date, only monoclonal antibodies have been shown to be effective for outpatients with COVID-19. Interferon lambda-1 is a type III interferon involved in innate antiviral responses with activity against respiratory pathogens. We aimed to investigate the safety and efficacy of peginterferon lambda in the treatment of outpatients with mild-to-moderate COVID-19. In this double-blind, placebo-controlled trial, outpatients with laboratory-confirmed COVID-19 were randomly assigned to a single subcutaneous injection of peginterferon lambda 180 μg or placebo within 7 days of symptom onset or first positive swab if asymptomatic. Participants were randomly assigned (1:1) using a computer-generated randomisation list created with a randomisation schedule in blocks of four. At the time of administration, study nurses received a sealed opaque envelope with the treatment allocation number. The primary endpoint was the proportion of patients who were negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA on day 7 after the injection, analysed by a χ Between May 18, and Sept 4, 2020, we recruited 30 patients per group. The decline in SARS-CoV-2 RNA was greater in those treated with peginterferon lambda than placebo from day 3 onwards, with a difference of 2·42 log copies per mL at day 7 (p=0·0041). By day 7, 24 (80%) participants in the peginterferon lambda group had an undetectable viral load, compared with 19 (63%) in the placebo group (p=0·15). After controlling for baseline viral load, patients in the peginterferon lambda group were more likely to have undetectable virus by day 7 than were those in the placebo group (odds ratio [OR] 4·12 [95% CI 1·15-16·73; p=0·029). Of those with baseline viral load above 10 Peginterferon lambda accelerated viral decline in outpatients with COVID-19, increasing the proportion of patients with viral clearance by day 7, particularly in those with high baseline viral load. Peginterferon lambda has potential to prevent clinical deterioration and shorten duration of viral shedding. The Toronto COVID-19 Action Initiative, University of Toronto, and the Ontario First COVID-19 Rapid Research Fund, Toronto General & Western Hospital Foundation.
Sections du résumé
BACKGROUND
To date, only monoclonal antibodies have been shown to be effective for outpatients with COVID-19. Interferon lambda-1 is a type III interferon involved in innate antiviral responses with activity against respiratory pathogens. We aimed to investigate the safety and efficacy of peginterferon lambda in the treatment of outpatients with mild-to-moderate COVID-19.
METHODS
In this double-blind, placebo-controlled trial, outpatients with laboratory-confirmed COVID-19 were randomly assigned to a single subcutaneous injection of peginterferon lambda 180 μg or placebo within 7 days of symptom onset or first positive swab if asymptomatic. Participants were randomly assigned (1:1) using a computer-generated randomisation list created with a randomisation schedule in blocks of four. At the time of administration, study nurses received a sealed opaque envelope with the treatment allocation number. The primary endpoint was the proportion of patients who were negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA on day 7 after the injection, analysed by a χ
FINDINGS
Between May 18, and Sept 4, 2020, we recruited 30 patients per group. The decline in SARS-CoV-2 RNA was greater in those treated with peginterferon lambda than placebo from day 3 onwards, with a difference of 2·42 log copies per mL at day 7 (p=0·0041). By day 7, 24 (80%) participants in the peginterferon lambda group had an undetectable viral load, compared with 19 (63%) in the placebo group (p=0·15). After controlling for baseline viral load, patients in the peginterferon lambda group were more likely to have undetectable virus by day 7 than were those in the placebo group (odds ratio [OR] 4·12 [95% CI 1·15-16·73; p=0·029). Of those with baseline viral load above 10
INTERPRETATION
Peginterferon lambda accelerated viral decline in outpatients with COVID-19, increasing the proportion of patients with viral clearance by day 7, particularly in those with high baseline viral load. Peginterferon lambda has potential to prevent clinical deterioration and shorten duration of viral shedding.
FUNDING
The Toronto COVID-19 Action Initiative, University of Toronto, and the Ontario First COVID-19 Rapid Research Fund, Toronto General & Western Hospital Foundation.
Identifiants
pubmed: 33556319
pii: S2213-2600(20)30566-X
doi: 10.1016/S2213-2600(20)30566-X
pmc: PMC7906707
pii:
doi:
Substances chimiques
Antiviral Agents
0
Interleukins
0
RNA, Viral
0
peginterferon lambda-1a
0T0250N43U
Polyethylene Glycols
3WJQ0SDW1A
Banques de données
ClinicalTrials.gov
['NCT04354259']
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
498-510Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
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