Document Detail


High versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study.
MedLine Citation:
PMID:  20131255     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Despite widespread use of colchicine, the evidence basis for oral colchicine therapy and dosing in acute gout remains limited. The aim of this trial was to compare low-dose colchicine (abbreviated at 1 hour) and high-dose colchicine (prolonged over 6 hours) with placebo in gout flare, using regimens producing comparable maximum plasma concentrations in healthy volunteers.
METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study compared self-administered low-dose colchicine (1.8 mg total over 1 hour) and high-dose colchicine (4.8 mg total over 6 hours) with placebo. The primary end point was > or = 50% pain reduction at 24 hours without rescue medication.
RESULTS: There were 184 patients in the intent-to-treat analysis. Responders included 28 of 74 patients (37.8%) in the low-dose group, 17 of 52 patients (32.7%) in the high-dose group, and 9 of 58 patients (15.5%) in the placebo group (P = 0.005 and P = 0.034, respectively, versus placebo). Rescue medication was taken within the first 24 hours by 23 patients (31.1%) in the low-dose group (P = 0.027 versus placebo), 18 patients (34.6%) in the high-dose group (P = 0.103 versus placebo), and 29 patients (50.0%) in the placebo group. The low-dose group had an adverse event (AE) profile similar to that of the placebo group, with an odds ratio (OR) of 1.5 (95% confidence interval [95% CI] 0.7-3.2). High-dose colchicine was associated with significantly more diarrhea, vomiting, and other AEs compared with low-dose colchicine or placebo. With high-dose colchicine, 40 patients (76.9%) had diarrhea (OR 21.3 [95% CI 7.9-56.9]), 10 (19.2%) had severe diarrhea, and 9 (17.3%) had vomiting. With low-dose colchicine, 23.0% of the patients had diarrhea (OR 1.9 [95% CI 0.8-4.8]), none had severe diarrhea, and none had vomiting.
CONCLUSION: Low-dose colchicine yielded both maximum plasma concentration and early gout flare efficacy comparable with that of high-dose colchicine, with a safety profile indistinguishable from that of placebo.
Authors:
Robert A Terkeltaub; Daniel E Furst; Katherine Bennett; Karin A Kook; R S Crockett; Matthew W Davis
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Publication Detail:
Type:  Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  62     ISSN:  1529-0131     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-14     Completed Date:  2010-05-04     Revised Date:  2011-12-06    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1060-8     Citation Subset:  AIM; IM    
Affiliation:
VAMC San Diego, and University of California, San Diego, CA 92161, USA. rterkeltaub@ucsd.edu
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00506883
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Arthralgia / chemically induced
Colchicine / administration & dosage,  adverse effects,  pharmacokinetics,  toxicity*
Continental Population Groups
Diarrhea / chemically induced
Dose-Response Relationship, Drug
Female
Gout / chemically induced*
Humans
Male
Melena / chemically induced
Middle Aged
Nausea / chemically induced
Pain / chemically induced
Placebos
Reference Values
Vomiting / chemically induced
Chemical
Reg. No./Substance:
0/Placebos; 64-86-8/Colchicine
Comments/Corrections
Comment In:
Arthritis Rheum. 2011 Nov;63(11):3647-8; author's reply 3648   [PMID:  21792828 ]
Arthritis Rheum. 2010 Oct;62(10):3126-7; author reply 3127-8   [PMID:  20617519 ]
Evid Based Med. 2010 Dec;15(6):170-1   [PMID:  20713543 ]

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