Colchicine for COVID-19 in the community (PRINCIPLE): a randomised, controlled, adaptive platform trial
Jienchi DorwardLy‐Mee YuGail HaywardBenjamin R. SavilleOghenekome GbinigieOliver van HeckeEmma OgburnPhilip EvansNicholas ThomasMihir PatelDuncan RichardsNicholas BerryMichelle A. DetryChristina SaundersMark FitzgeraldVictoria HarrisMilensu ShanyindeSimon de LusignanMonique AnderssonChristopher ButlerRichard Hobbs
32
Citation
27
Reference
10
Related Paper
Citation Trend
Abstract:
Background Colchicine has been proposed as a COVID-19 treatment. Aim To determine whether colchicine reduces time to recovery and COVID-19-related admissions to hospital and/or deaths among people in the community. Design and setting Prospective, multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial (PRINCIPLE). Method Adults aged ≥65 years or ≥18 years with comorbidities or shortness of breath, and unwell for ≤14 days with suspected COVID-19 in the community, were randomised to usual care, usual care plus colchicine (500 µg daily for 14 days), or usual care plus other interventions. The co-primary endpoints were time to first self-reported recovery and admission to hospital/death related to COVID-19, within 28 days, analysed using Bayesian models. Results The trial opened on 2 April 2020. Randomisation to colchicine started on 4 March 2021 and stopped on 26 May 2021 because the prespecified time to recovery futility criterion was met. The primary analysis model included 2755 participants who were SARS-CoV-2 positive, randomised to colchicine ( n = 156), usual care ( n = 1145), and other treatments ( n = 1454). Time to first self-reported recovery was similar in the colchicine group compared with usual care with an estimated hazard ratio of 0.92 (95% credible interval (CrI) = 0.72 to 1.16) and an estimated increase of 1.4 days in median time to self-reported recovery for colchicine versus usual care. The probability of meaningful benefit in time to recovery was very low at 1.8%. COVID-19-related admissions to hospital/deaths were similar in the colchicine group versus usual care, with an estimated odds ratio of 0.76 (95% CrI = 0.28 to 1.89) and an estimated difference of −0.4% (95% CrI = −2.7 to 2.4). Conclusion Colchicine did not improve time to recovery in people at higher risk of complications with COVID-19 in the community.Keywords:
Colchicine
Intention-to-treat analysis
Cite
Citations (0)
Cite
Citations (0)
Controversy exists concerning the necessary margin of excision for cutaneous melanoma 2 mm or greater in thickness.
Margin (machine learning)
Surgical excision
Cite
Citations (479)
Cite
Citations (0)
Ground-glass opacity
Cite
Citations (54)
The prognostic role of survivin in colorectal carcinoma remains controversial. This meta-analysis aimed to explore the association between survivin expression and survival outcomes in patients with colorectal carcinoma. A comprehensive literature search for relevant studies published up to April 2013 was performed using PubMed, MEDLINE and ISI Web of Science. Only articles in which survivin was detected by immunohistochemical staining were included. This meta-analysis was done using STATA and Review Manager. A total of 1784 patients from 14 studies were included in the analysis. Our results showed that survivin overexpression in patients with colorectal carcinoma was significantly associated with poor overall survival (hazard ratio, 1.505; 95% confidence interval, 1.197–1.893; P = 0.000) and disease-free survival (hazard ratio, 2.323; 95% confidence interval, 1.687–3.199; P = 0.000). The results indicated that a significant relationship between survivin expression and overall survival was also exhibited in studies with an Asian country (hazard ratio, 1.684; 95% confidence interval, 1.477–1.921), patient number >100 (hazard ratio, 1.604; 95% confidence interval, 1.371–1.877), the cut-off level <50% (hazard ratio, 1.449; 95% confidence interval, 1.045–2.010), the percentage of survivin overexpression >50% (hazard ratio, 1.528; 95% confidence interval, 1.056–2.211) and the hazard ratio estimated (hazard ratio, 1.643; 95% confidence interval, 1.262–2.139). Moreover, upregulation of survivin was associated with stages (III/IV vs. I/II: odds ratio, 1.08; 95% confidence interval, 0.80–1.46), the depth of invasion (T3/T4 vs. T1/T2: odds ratio, 1.79; 95% confidence interval 0.67–4.74), lymph node metastasis (positive vs. negative: odds ratio, 1.49; 95% confidence interval, 0.99–2.26), distant metastasis (positive vs. negative: odds ratio, 2.37; 95% confidence interval, 0.99–5.72) and grade of differentiation (well/moderate vs. poor: odds ratio, 1.02; 95% confidence interval, 0.43–2.41), but without significance. The present meta-analysis indicated that upregulation of survivin was associated with poor prognosis in patients with colorectal carcinoma.
Survivin
Cite
Citations (26)
Cite
Citations (0)
Lymphadenectomy
Cite
Citations (6)