Colchicine, when given in addition to conventional therapy, was more effective than placebo in reducing the incidence of recurrence and the persistence of symptoms of pericarditis in a randomised controlled trial. This is the first time that the efficacy of colchicine in preventing recurrent episodes of pericarditis has been demonstrated in a double-blind multicentre randomised trial.
" Recurrence," said investigator Dr Massimo Imazio from the Maria Vittoria Hospital in Turin, Italy,"is the most common complication of pericarditis, affecting between 20 and 50% of patients. Recurrences can be frequent and may seriously affect quality of life, cause hospital readmission, and increase management costs. There has been some preliminary data from non-randomised observational studies and two single-centre open-label randomised studies suggesting that colchicine may be a safe and useful drug for preventing these recurrences. Our aim was to test these suggestions in a multicentre double-blind randomised placebo-controlled trial."
Indeed, it was on the basis of such non-randomised observational findings (as well as expert opinion) that colchicine was recommended for the treatment of recurrent pericarditis (class I recommendation) in the 2004 guidelines on pericardial diseases of the European Society of Cardiology.
The CORP trial, an independent non-sponsored study and the first multicentre double-blind randomised trial of colchicine in the secondary prevention of pericarditis, was performed in four centres in Italy and recruited 120 consecutive patients with a first episode of recurrent pericarditis. The primary endpoint of the study was the recurrence rate at 18 months; the secondary endpoints were symptom persistence at 72 hours, remission rate at one week, the number of recurrences, time to first recurrence, disease-related hospitalisation, cardiac tamponade, and constrictive pericarditis rates.
Colchicine was given as adjunctive therapy at an initial dose of 1.0-2.0 mg for the first day and a maintenance dose of 0.5-1.0 mg daily for the following six months. The lower dose (initial dose: 0.5 mg every 12 hours and maintenance dose 0.5 mg daily) was given to patients under 70 kg in weight or intolerant of the highest dose (initial dose 1.0 mg every 12 hours and maintenance dose of 0.5 mg every 12 hours).
Results showed that colchicine significantly reduced the incidence of recurrences at 18 months when compared to placebo (24% vs. 55%, p<0.001). In addition, symptom persistence at 72 hours was significantly lower in the colchicine group than in the placebo group (23.3% vs. 53.3%, p=0.001) as were the mean number of recurring episodes. The rate of remission at one week was higher in those patients given colchicine than placebo (82% vs. 48%; p<0.001), as was the time to a subsequent recurrence. The rate of side effects was similar in the colchicine and placebo groups (7% vs. 7%; p>0.99).
Commenting on the results, Dr Imazio said: "When added to empiric anti-inflammatory therapy, colchicine appears to be a safe low-cost drug for rapid symptom relief, improved remission rates at one week, and reduced recurrence after an initial episode of recurrent pericarditis.
"However, our findings might not be generalisable to other settings or other patient populations. This trial only addressed the use of colchicine following a first recurrence of pericarditis, and not in patients with multiple recurrences. We recruited only adult patients, and thus cannot apply our results to paediatric populations. We excluded patients with bacterial or neoplastic pericarditis, patients with transaminases elevation or severe liver disease, elevated creatinine, patients with myopathy, blood dyscrasias or gastrointestinal disease, pregnant and lactating women, as well as women of childbearing potential and not using contraception.
"It should also be noted that colchicine is not registered for the prevention of pericarditis and its use for this indication is off-label."
A full report of this study will be published simultaneously online (and under the same embargo conditions) by the Annals of Internal Medicine.