Protocol for the Controlled evaLuation of Angiotensin Receptor blockers for COVID-19 respIraTorY disease (CLARITY): a randomised controlled trial.
Angiotensin receptor blockers
Bayesian adaptive design
COVID-19
RCT
Renin-angiotensin system
Journal
Trials
ISSN: 1745-6215
Titre abrégé: Trials
Pays: England
ID NLM: 101263253
Informations de publication
Date de publication:
28 Aug 2021
28 Aug 2021
Historique:
received:
07
06
2021
accepted:
06
08
2021
entrez:
29
8
2021
pubmed:
30
8
2021
medline:
1
9
2021
Statut:
epublish
Résumé
SARS-CoV-2 binds to membrane-bound angiotensin-converting enzyme 2 (ACE2) which may result in downregulation of membrane-bound ACE2. ACE2 is a key regulator of the renin-angiotensin system (RAS) and is responsible for degrading angiotensin II and thereby counteracting its pro-inflammatory, pro-fibrotic effects mediated through the angiotensin II type 1 receptor (AT1R). As AT1R is directly blocked by angiotensin receptor blockers (ARBs), these agents may offer a safe, low-cost solution for reducing COVID-19 respiratory outcomes. CLARITY is a pragmatic, adaptive, two-arm, multi-centre, comparative effectiveness phase III randomised controlled trial that examines whether ARBs reduce COVID-19 severity among high-risk patients. Recruiting in India and Australia, the trial will compare treatment with a maximum tolerated daily dose of an ARB to standard of care. Treatment allocation is blinded in India but open-label in Australia due to interruptions to placebo supply in the latter. The primary endpoint is a 7-point ordinal scale of clinical states, ranging from no limitation of activities (category 1) to death (category 7), assessed on day 14. Secondary outcomes include the 7-point scale assessed at day 28 and 28- and 90-day mortality. The design adapts the sample size based on accumulating data via frequent interim analyses and the use of predictive probability to determine whether the current sample size is sufficient or continuing accrual would be futile. The trial commenced recruitment on 18 August 2020. ClinicalTrials.gov, NCT04394117 . Registered on 19 May 2020. Clinical Trial Registry of India: CTRI/2020/07/026831).
Sections du résumé
BACKGROUND
BACKGROUND
SARS-CoV-2 binds to membrane-bound angiotensin-converting enzyme 2 (ACE2) which may result in downregulation of membrane-bound ACE2. ACE2 is a key regulator of the renin-angiotensin system (RAS) and is responsible for degrading angiotensin II and thereby counteracting its pro-inflammatory, pro-fibrotic effects mediated through the angiotensin II type 1 receptor (AT1R). As AT1R is directly blocked by angiotensin receptor blockers (ARBs), these agents may offer a safe, low-cost solution for reducing COVID-19 respiratory outcomes.
METHODS AND DISCUSSION
RESULTS
CLARITY is a pragmatic, adaptive, two-arm, multi-centre, comparative effectiveness phase III randomised controlled trial that examines whether ARBs reduce COVID-19 severity among high-risk patients. Recruiting in India and Australia, the trial will compare treatment with a maximum tolerated daily dose of an ARB to standard of care. Treatment allocation is blinded in India but open-label in Australia due to interruptions to placebo supply in the latter. The primary endpoint is a 7-point ordinal scale of clinical states, ranging from no limitation of activities (category 1) to death (category 7), assessed on day 14. Secondary outcomes include the 7-point scale assessed at day 28 and 28- and 90-day mortality. The design adapts the sample size based on accumulating data via frequent interim analyses and the use of predictive probability to determine whether the current sample size is sufficient or continuing accrual would be futile. The trial commenced recruitment on 18 August 2020.
TRIAL REGISTRATION
BACKGROUND
ClinicalTrials.gov, NCT04394117 . Registered on 19 May 2020. Clinical Trial Registry of India: CTRI/2020/07/026831).
Identifiants
pubmed: 34454580
doi: 10.1186/s13063-021-05521-0
pii: 10.1186/s13063-021-05521-0
pmc: PMC8397850
doi:
Substances chimiques
Angiotensin Receptor Antagonists
0
Angiotensin-Converting Enzyme Inhibitors
0
Banques de données
ClinicalTrials.gov
['NCT04394117']
Types de publication
Clinical Trial Protocol
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
573Subventions
Organisme : National Health and Medical Research Council
ID : APP2002277
Informations de copyright
© 2021. The Author(s).
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