Asthma Clinical Research Network (ACRN)
Colchicine In Moderate Asthma (CIMA)
In patients with moderate asthma who require ICS for control of symptoms and lung function, colchicine offers no therapeutic benefit as measured by maintenance of control when ICS are administered.
Men and women (18-60 yrs) with moderate asthma and pre-bronchodilator FEV1 values 55-90% of predicted were recruited. Moderate asthma was defined as having symptoms poorly regulated by episodic administration of a ß-agonist and by the need for ICS at doses ranging from 336 to 1600 µg/day for symptom control for at least 30 days prior to entry. Eligible subjects were required to have >12% increase in FEV1 in response to inhaled albuterol or a methacholine PC20 £ 8mg/ml within 6 months prior to entry. Qualifying subjects enrolled in a 4-week run-in period in which usual medications were discontinued and all subjects were given triamcinolone acetonide, 800 µg/day, and albuterol MDI as needed for symptom control. After 2 weeks of stabilization on triamcinolone, all subjects were given colchicine (0.6 mg bid) for the final 2 weeks of the run-in. Subjects whose FEV1 remained 55% of predicted and who demonstrated compliance with study procedures at week 4 were randomized to either remain on colchicine or take placebo in a 6-week double-blind treatment phase. At the same time, all subjects discontinued inhaled triamcinolone. Clinic visits were scheduled at 2-week intervals where subjects were examined and performed spirometry. The primary outcome variable was treatment failure, defined as a significant decrease in FEV1, decrease in PEF, increase in symptoms, or increase rescue albuterol use relative to baseline.
Enrollment began in February 1996 and the trial ended in July 1996. Seventy-one subjects (52% female, 38% minority) were randomized with 36 to the placebo group and 35 to the colchicine group. There were no significant differences between groups at entry in terms of age, gender, ethnicity, FEV1, or reported dosages of ICS used prior to entry. Two subjects, one from each group, withdrew after randomization for reasons unrelated to asthma. Compliance with colchicine use was 94.4% as measured by capsule counts. The percentage of subjects identified as treatment failures was 60% in the colchicine group and 56% in the placebo group (logrank p-value = 0.38). Changes in FEV1, AM PEF, PEF variability, symptom scores, rescue ß-agonist use, and quality of life scores between baseline and the study end point also did not differ significantly between the groups. The major publication appeared in AJRCCM:
Fish JE, Peters SP, Chambers CV, McGeady SG, Epstein KR, Boushey HA, Cherniack RM, Chinchilli VM, Drazen JM, Fahy JV, Hurd SS, Israel E, Lazarus SC, Lemanske RF, Martin RJ, Mauger EA, Sorkness C, Szefler SJ. An evaluation of colchicine as an alternative to inhaled corticosteroids in moderate asthma. American Journal of Respiratory and Critical Care Medicine 1997; 156:1165-1171.