COlchicine for Recurrent Pericarditis - CORP

Aug 28, 2011
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Maria Vittoria Hospital, Torino, Italy. Acarpia Lda (Madeira, Portugal) provided supply of drug/placebo as unrestricted grant.
Date Presented:
01/01/2011
Date Published:
01/01/2011
Date Updated:
08/28/2011
Original Posted Date:
08/28/2011
References

Description:

Recurrent pericarditis is one of the most common and troublesome complications of acute pericarditis, occurring in 10-50% of patients with pericarditis. Colchicine has been shown to be promising for the secondary prevention of recurrent pericarditis in the CORE (recurrent pericarditis) and COPE (acute pericarditis) open-label studies. The current trial sought to compare the safety and efficacy of colchicine compared with placebo, in addition to standard therapy, in patients with recurrent pericarditis, in a double-blind randomized controlled fashion.

Hypothesis:

Colchicine would be superior to placebo in reducing recurrent pericarditis in patients with a first episode of recurrent pericarditis.

Study Design

  • Placebo Controlled
  • Blinded
  • Randomized
  • Parallel

Patient Populations:

  • Definite diagnosis of recurrent pericarditis (first recurrence), defined as previous history of acute pericardits with recurrent chest pain and one or more of the following signs: (a) fever, (b) pericardial friction rubs, (c) electrocardiographic changes, (d) echocardiographic evidence of new or worsening pericardial effusion, and (e) elevations in the white blood cell count, erythrocyte sedimentation rate, or C-reactive protein
  • Age ≥18 years

    Number of screened applicants: 140
    Number of enrollees: 120
    Duration of follow-up: 18 months
    Mean patient age: 47.6
    Percentage female: 55%

Exclusions:

  • First attack of acute pericarditis or second or subsequent recurrence
  • Tuberculous, neoplastic, or purulent etiologies
  • Known severe liver disease or current transaminases >1.5 times the upper normal limit
  • Current serum creatinine ≥2.5 mg/dl
  • Known myopathy or current serum creatine kinase above the upper normal limit
  • Known blood dyscrasias or gastrointestinal disease
  • Pregnant and lactating women (in whom colchicine is considered contraindicated)
  • Women of childbearing potential not protected by a contraception method
  • Known hypersensitivity to colchicine
  • Current or previous treatment with colchicine for any indications

Primary Endpoints:

  • Recurrent pericarditis at 18 months

Secondary Endpoints:

  • Symptom-persistence at 72 hours
  • Remission rate at 1 week
  • Number of recurrences
  • Time to first recurrence
  • Disease-related hospitalization
  • Cardiac tamponade
  • Constrictive pericarditis rates

Drug/Procedures Used:

Patients were randomized to either conventional treatment with placebo or conventional therapy with colchicine 1 mg BID for 24 hours, then 0.5 mg BID for 6 months (0.5 mg BID for 1 day then 0.5 mg QD for 1 month if weight <70 kg).

Concomitant Medications:

Aspirin 800-1000 mg orally every 8 hours (or ibuprofen 600 mg every 8 hours) for 7-10 days, with gradual tapering over 3-4 weeks

Principal Findings:

A total of 120 patients were randomized, 60 to colchicine and 60 to placebo. Baseline characteristics were fairly similar between the two arms. The majority of patients (82%) had idiopathic pericarditis; about 18% had a possible autoimmune cause. About 6% had undergone prior cardiac surgery, 11% prior myocardial infarction, and 9% had been treated with corticosteroids before.

At 18 months, recurrence rate was 24% in the colchicine group versus 55% in the placebo group (relative risk [RR] 0.44, 95% confidence interval [CI] 0.27-0.73, p < 0.001). This corresponded to a number needed to treat of three patients. Colchicine also significantly reduced the persistence of symptoms at 72 hours (23% vs. 53%, RR 0.46, 95% CI 0.26-0.73, p = 0.001), and the mean number of recurrences (0.1 vs. 1, p < 0.001). At the same time, colchicine increased the remission rate at 1 week (82% vs. 48%, p < 0.001), and prolonged the time to a subsequent recurrence (2.5 vs. 1 months, p < 0.001). No differences were noted in the incidence of readmission or cardiac tamponade; no cases of constrictive pericarditis were recorded in either arm.

Overall adverse effects were similar (7%), including gastrointestinal (7% vs. 5%) and hepatotoxicity (0% vs. 2%). Drug withdrawal rates were similar (8% vs. 7%).

Interpretation:

The results of this trial indicate that low-dose colchicine, in addition to empiric anti-inflammatory therapy, may be safe and efficacious in reducing rates of recurrent pericarditis in patients with mostly idiopathic recurrent pericarditis. It also improves remission rates and hastens symptom resolution. These are interesting findings and extend earlier findings by the same investigators with colchicine.

Although infrequent, recurrent pericarditis can be quite troublesome, and sometime debilitating; treatment options thus far have been limited either by efficacy or side effects. Colchicine may prove to be a valuable addition to the treatment armamentarium for recurrent pericarditis. Further studies will need to outline whether it can be used as a solitary agent, and whether it has any role in preventing pericarditis in patients at high-risk, such as those undergoing pericardiotomy.

References:

Imazio M, Brucato A, Cemin R, et al., on behalf of the CORP Investigators. Colchicine for Recurrent Pericarditis (CORP): A Randomized Trial. Ann Intern Med 2011;155:409-414.

Presented by Dr. Massimo Imazio at the European Society of Cardiology Congress, Paris, France, August 2011.

Keywords: Risk, Myocardial Infarction, Pericarditis, Constrictive, Blood Sedimentation, Colchicine, Leukocyte Count, Pericardiectomy, Recurrence, C-Reactive Protein, Secondary Prevention, Chest Pain, Cardiac Surgical Procedures, Pericardial Effusion, Cardiac Tamponade


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