Colchicine for Recurrent Pericarditis 2 - CORP-2

Mar 30, 2014
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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:
Azienda Sanitaria 3 of Torino (now ASLTO2) within the Italian National Health Service. Acarpia (Madeira, Portugal) provided the study drug and placebo as an unrestricted grant.
Date Presented:
01/01/2014
Date Published:
01/01/2014
Date Updated:
03/30/2014
Original Posted Date:
03/30/2014
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), COPE (acute pericarditis) open-label studies, and the CORP (first recurrent pericarditis) trials.

The current trial sought to compare the safety and efficacy of colchicine as compared with placebo, in addition to standard therapy, in patients with multiple recurrent episodes of pericarditis in a double-blind, randomized, controlled fashion.

Hypothesis:

Colchicine would be superior to placebo in reducing recurrent pericarditis in patients with multiple episodes (≥2) of recurrent pericarditis.

Study Design

  • Placebo Controlled
  • Randomized
  • Blinded
  • Parallel

Patient Populations:

  • Definite diagnosis of recurrent pericarditis. 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
  • Consecutive patients ages ≥18 years with two or more recurrences of pericarditis (idiopathic, viral, post-cardiac injury, or caused by connective tissue disease)

    Number of screened applicants: 260
    Number of enrollees: 240
    Duration of follow-up: 6 months
    Mean patient age: 48.8
    Percentage female: 50%

Exclusions:

  • Tuberculous, neoplastic, or purulent pericarditis etiology
  • Severe liver disease or current aminotransferase concentrations more than 1.5 times the upper limit of the normal
  • Serum creatinine concentration >22,100 μmol/L
  • Skeletal myopathy or serum creatine kinase concentration more than the upper limit of the normal
  • Blood dyscrasia
  • Inflammatory bowel disease
  • Hypersensitivity to colchicine or other contraindication to colchicine
  • Current treatment with colchicine
  • Life expectancy of ≤18 months
  • Pregnant or lactating women or women of childbearing potential not using contraception
  • Evidence of myopericarditis, as indicated by any increase of serum troponin concentration

Primary Endpoints:

  • Recurrent pericarditis at 6 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 0.5 mg BID for 6 months (0.5 mg daily for 1 month if weight was ≤70 kg).

Concomitant Medications:

Aspirin 800 mg orally every 8 hours, ibuprofen 600 mg every 8 hours, or indomethacin 50 mg every 8 hours for 7-10 days with gradual tapering over 3-4 weeks. Corticosteroid treatment (prednisone 0.2-0.5 mg/kg/day for 4 weeks, then tapered) was given to patients already taking corticosteroids or who had contraindications to aspirin, ibuprofen, and indomethacin, or a history of intolerance. All patients also received a proton pump inhibitor for gastrointestinal prophylaxis.

Principal Findings:

A total of 240 patients were randomized at four centers in Italy, 120 to colchicine and 120 to placebo. Baseline characteristics were fairly similar between the two arms. The majority of patients (82%) had idiopathic pericarditis; approximately 7% had a possible connective tissue disorder, and the rest were thought to have post-cardiac injury syndrome. Approximately 4% had undergone prior cardiac surgery, 8% prior myocardial infarction, and 6% had been treated with corticosteroids before. Echo evidence of a pericardial effusion was observed in 58%.

At 6 months, recurrence rate was 21.6% in the colchicine group versus 42.5% in the placebo group (relative risk, 0.46; 95% confidence interval, 0.30-0.72; p = 0.0009). This corresponded to a number needed to treat of five patients. Colchicine also significantly reduced the persistence of symptoms at 72 hours (19.2% vs. 44.2%, p = 0.0001), and the mean number of recurrences (0.58 vs. 0.87, p = 0.0004). At the same time, colchicine increased the remission rate at 1 week (83.3% vs. 59.2%, p = 0.0001), and reduced pericarditis-related readmissions (1.7% vs. 10%, p = 0.013). There was a nonsignificant prolongation of the time to a subsequent recurrence (11.1 vs. 4.2 months, p = 0.22).

Overall adverse effects were similar (10%), including gastrointestinal (7.5% vs.75%) and elevation of liver enzymes over the upper limit of normal (2.5% vs. 0.8%). Drug withdrawal rates were similar (6.7% vs. 5.8%).

Interpretation:

The results of the CORP-2 trial are remarkably similar to the original CORP trial, and indicate that low-dose colchicine, in addition to empiric anti-inflammatory therapy, may be safe and efficacious in reducing recurrence rates due to recurrent pericarditis in patients with mostly idiopathic recurrent pericarditis. It also improves remission rates, and hastens symptom resolution.

These are important findings, and extend earlier findings by the same investigators with colchicine. They suggest a primary role for colchicine in the management of patients with pericarditis.

References:

Imazio M, Belli R, Brucato A, et al. Efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): a multicentre, double-blind, placebo-controlled, randomised trial. Lancet 2014;383:2232-7.

Editorial: Cacoub PP. Colchicine for treatment of acute or recurrent pericarditis. Lancet 2014;383:2193-4.

Presented by Dr. Massimo Imazio at the American College of Cardiology Annual Scientific Session, Washington, DC, March 30, 2014.

Keywords: Connective Tissue Diseases, Myocardial Infarction, Colchicine, Blood Sedimentation, Leukocyte Count, Pericarditis, Italy, Recurrence, C-Reactive Protein, Secondary Prevention, Chest Pain, Liver, Cardiac Surgical Procedures, Pericardial Effusion, ACC Annual Scientific Session


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