Beneficial effects of colchicine for moderate to severe COVID-19: a randomised, double-blinded, placebo-controlled clinical trial
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
To evaluate whether the addition of colchicine to standard treatment for COVID-19 results in better outcomes.
Design
We present the results of a randomised, double-blinded, placebo-controlled clinical trial of colchicine for the treatment of moderate to severe COVID-19, with 75 patients allocated 1:1 from 11 April to 30 August 2020. Colchicine regimen was 0.5 mg thrice daily for 5 days, then 0.5 mg twice daily for 5 days. The primary endpoints were the need for supplemental oxygen, time of hospitalisation, need for admission and length of stay in intensive care unit and death rate.
Results
Seventy-two patients (36 for placebo and 36 for colchicine) completed the study. Median (and IQR) time of need for supplemental oxygen was 4.0 (2.0–6.0) days for the colchicine group and 6.5 (4.0–9.0) days for the placebo group (p<0.001). Median (IQR) time of hospitalisation was 7.0 (5.0–9.0) days for the colchicine group and 9.0 (7.0–12.0) days for the placebo group (p=0.003). At day 2, 67% versus 86% of patients maintained the need for supplemental oxygen, while at day 7, the values were 9% versus 42%, in the colchicine and the placebo groups, respectively (log rank; p=0.001). Two patients died, both in placebo group. Diarrhoea was more frequent in the colchicine group (p=0.26).
Conclusion
Colchicine reduced the length of both, supplemental oxygen therapy and hospitalisation. The drug was safe and well tolerated. Once death was an uncommon event, it is not possible to ensure that colchicine reduced mortality of COVID-19.
Trial registration number
RBR-8jyhxh.
Article activity feed
-
SciScore for 10.1101/2020.08.06.20169573: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The trial is registered on the National Registry under the alphanumeric code RBR-8jyhxh (http://www.ensaiosclinicos.gov.br/rg/RBR-8jyhxh/) and it was approved by National Ethics Committee (CONEP; CAAE: 30248420.9.3001.5403). Randomization Trial design: We conducted a randomized, double-blinded, placebo controlled clinical trial to evaluate the use of colchicine for the treatment of hospitalized patients with moderate to severe COVID-19. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. …
SciScore for 10.1101/2020.08.06.20169573: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The trial is registered on the National Registry under the alphanumeric code RBR-8jyhxh (http://www.ensaiosclinicos.gov.br/rg/RBR-8jyhxh/) and it was approved by National Ethics Committee (CONEP; CAAE: 30248420.9.3001.5403). Randomization Trial design: We conducted a randomized, double-blinded, placebo controlled clinical trial to evaluate the use of colchicine for the treatment of hospitalized patients with moderate to severe COVID-19. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our clinical trial has some limitations. The most evident is the reduced number of patients and the recruitment in a single center. To balance this, the blinding and the control by a placebo arm strengthen our finds. The absence of mechanistic investigations, e.g., measures of the plasmatic levels of cytokines, is another limitation. Our exclusion criteria were some kind of restrictive, such as the prohibition of some cardiovascular drugs. Much of this concern was related to drugs that could impair colchicine metabolism or excretion, but some concern was also due to the potential hazardous effect of hydroxychloroquine and azithromycin combined use for myocardial fibers. Finally, as patients were discharged, the number of blood samples reduced through the first week of observation and beyond, once it would not be appropriate to summon up the patients for new blood collections due to SARS-CoV-2 transmission possibility.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
-
-
-
SciScore for 10.1101/2020.08.06.20169573: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement The trial is registered on the National Registry under the alphanumeric code RBR8jyhxh (http://www.ensaiosclinicos.gov.br/rg/RBR-8jyhxh/) and it was approved by National Ethics Committee (CONEP; CAAE: 30248420.9.3001.5403). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
Our clinical …
SciScore for 10.1101/2020.08.06.20169573: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement The trial is registered on the National Registry under the alphanumeric code RBR8jyhxh (http://www.ensaiosclinicos.gov.br/rg/RBR-8jyhxh/) and it was approved by National Ethics Committee (CONEP; CAAE: 30248420.9.3001.5403). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
Our clinical trial has some limitations. The most evident is the reduced number of patients and the recruitment in a single center. To balance this, the blinding and the control by a placebo arm strengthen our finds. The absence of mechanistic investigations, e.g., measures of the plasmatic levels of cytokines, is another limitation. Our exclusion criteria were some kind of restrictive, such as the prohibition of some cardiovascular drugs. Much of this concern was related to drugs that could impair colchicine metabolism or excretion, but some concern was also due to the potential hazardous effect of hydroxychloroquine and azithromycin combined use for myocardial fibers. Finally, as patients were discharged, the number of blood samples reduced through the first week of observation and beyond, once it would not be appropriate to summon up the patients for new blood collections due to SARS-CoV-2 transmission possibility.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
About SciScore
SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.
-