Investigation of the Management of Pericarditis - IMPI

Sep 02, 2014
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Canadian Institutes of Health Research, Canadian Network and Centre for Trials Internationally, Population Health Research Institute, South African Medical Research Council
Date Presented:
01/01/2014
Date Published:
01/01/2014
Date Updated:
09/02/2014
Original Posted Date:
09/02/2014
References

Description:

Tuberculous pericarditis is a highly morbid and mortal disease, for which the optimal therapy is not known. The goal of the trial was to evaluate treatment with glucocorticoid therapy and Mycobacterium indicus pranii immunotherapy in participants with tuberculous pericarditis.

Hypothesis:

Glucocorticoid therapy and M. indicus pranii immunotherapy will reduce adverse cardiovascular events.

Study Design

  • Blinded
  • Parallel
  • Placebo Controlled
  • Randomized
  • Stratified

Patient Populations:

  • Participants were eligible for enrollment if they had a pericardial effusion, definite or probable tuberculous pericarditis, and had received anti-tuberculosis treatment <1 week before enrollment.

    Number of enrollees: 2,650 total patients
    Duration of follow-up (median): 637 days, 721 days
    Mean patient age: 39 years
    Percentage female: 45%

Exclusions:

  • Alternative cause of the pericardial disease
  • Use of glucocorticoids in the last month
  • Allergy to M. indicus pranii immunotherapy
  • Pregnancy

Primary Endpoints:

  • Death, tamponade requiring pericardiocentesis, or constrictive pericarditis

Secondary Endpoints:

  • Individual components of the primary outcome

Drug/Procedures Used:

Participants with tuberculous pericarditis and a high prevalence of human immunodeficiency virus (HIV) were randomized by factorial design to prednisolone (n = 706) vs. placebo (n = 694), and to M. indicus pranii immunotherapy (five intradermal injections over 3 months (n = 625) vs. placebo injections (n = 625).

Prednisolone was administered at a dose of 120 mg per day for the first week, then 90 mg per day for the second week, then 60 mg per day for the third week, then 30 mg per day for the fourth week, then 15 mg per day for the fifth week, then 5 mg per day for the sixth week.

Principal Findings:

Overall, 2,650 patients were randomized. The mean age was 39 years, 45% were women, 65% had a large pericardial effusion, 61% had pericardiocentesis performed, and 67% were HIV positive. A definite diagnosis of tuberculous pericarditis was only made in 16%.

In the glucocorticoid stratum: At a median of 637 days, the primary outcome occurred in 23.8% of the prednisolone group vs. 24.5% of the placebo group (p = 0.66).

- Death: 18.8% vs. 16.6% (p = 0.26), respectively
- Cardiac tamponade: 3.1% vs. 4.0% (p = 0.37), respectively
- Constrictive pericarditis: 4.4% vs. 7.8% (p = 0.009), respectively
- Hospitalization: 20.7% vs. 25.2% (p = 0.04), respectively
- Cancer: 1.05 cases/100 person-years vs. 0.32 cases/100 person-years (p = 0.03), respectively

In the immunotherapy group: At a median of 721 days, the primary outcome occurred in 25.0% of the immunotherapy group vs. 24.3% of the placebo group (p = 0.81).

- Death: 19.0% vs. 17.8% (p = 0.59), respectively
- Cardiac tamponade: 3.5% vs. 3.5% (p = 0.98), respectively
- Constrictive pericarditis: 5.8% vs. 5.9% (p = 0.89), respectively
- Hospitalization: 24.3% vs. 22.6% (p = 0.46), respectively
- Cancer: 0.92 cases/100 person-years vs. 0.24 cases/100 person-years (p = 0.03), respectively

Interpretation:

Among participants with tuberculous pericarditis, neither prednisolone therapy nor M. indicus pranii immunotherapy was associated with a reduction in the primary outcome. Prednisolone therapy was effective at reducing the incidence of constrictive pericarditis; however, both therapies were associated with an increased incidence of HIV-related cancers. One potential reason for the lack of benefit was the relatively low proportion of definite tuberculous pericarditis.

References:

Mayosi BM, Ntsekhe M, Bosch J, et al., on behalf of the IMPI Trial Investigators. Prednisolone and Mycobacterium indicus pranii in Tuberculous Pericarditis. N Engl J Med 2014;Sep 2:[Epub ahead of print].

Presented by Dr. Bongani Mayosi at the European Society of Cardiology Congress, Barcelona, Spain, September 2, 2014.

Keywords: Neoplasms, Pericarditis, Constrictive, Morbidity, Prednisolone, Immunotherapy, Pericarditis, Tuberculous, Pericardiocentesis, Prevalence, Mycobacterium, Glucocorticoids, Pericardial Effusion, Cardiac Tamponade, ESC Congress


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