Trial ISRCTN86534580; EudraCT 2020-001209-22
Publication PRINCIPLE - Yu LM, Lancet (2021) (published paper)
Dates: 2020-11-27 to 2021-03-31
Funding: Public/non profit (UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research)
Conflict of interest: Yes
Methods | |
RCT Blinding: Unblinded | |
Location :
Multicenter / UK Follow-up duration (days): 28 | |
Inclusion criteria |
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Exclusion criteria |
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Interventions | |
Treatment
Budesonide 800 mcg (2 x 400 mcg inhalations) twice a day for 14 days. |
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Control
Standard care | |
Participants | |
Randomized participants : Budesonide =1073 Standard care=NR | |
Characteristics of participants N= 1073 Mean age : NR 835 males Severity : Mild: n= 1719/ Asymptomatic: n=0 Number of vaccinated participants: NR | |
Primary outcome | |
In the register 1. Time taken to self-reported recovery, defined as the first instance that a participant reports feeling recovered from possible COVID-19; 2. Hospitalisation and/or death. Both collected within 28 days of randomization (ISRCTN). | |
In the report 1) Time to first reported recovery defined as the first instance that a participant reports feeling recovered; and 2) Hospitalization or death related to COVID-19. | |
Documents available |
Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication:
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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 published/pre-print article, the trial registry, protocol and statistical analysis plan were used in data extraction and assessment of risk of bias. PRINCIPLE is an adaptive platform trial. The primary outcome was changed from hospitalization or death within 28 days to first instance that a participant reports feeling recovered on the recommendation of the Trial Management Group and Trial Steering and with ethical approval due to low incidence of the original outcome. The Data Monitoring and Safety Committee determined that the pre-specified superiority criterion was met on time to recovery, in both the SARS-CoV-2 positive population and the overall study population. Recruitment was stopped because the Trial Steering Committee decided that accumulating further data to reach pre-specified futility or superiority criteria on hospitalization/death was unlikely due to the successful vaccine rollout and lower than originally anticipated event rate. Therefore the study did not achieve the target sample size specified in the trial registry.
On 16th of August, 2021, this study was updated based on the published report. |