In order to bring you the best possible user experience, this site uses Javascript. If you are seeing this message, it is likely that the Javascript option in your browser is disabled. For optimal viewing of this site, please ensure that Javascript is enabled for your browser.
Did you know that your browser is out of date? To get the best experience using our website we recommend that you upgrade to a newer version. Learn more.

We use cookies to optimise the design of this website and make continuous improvement. By continuing your visit, you consent to the use of cookies. Learn more

IMPI Steroid Study: A Trial of Adjunctive Prednisolone in Tuberculous Pericarditis

ESC Congress 2014 - Hot Line report

Pericardial Disease


 

Presentation

By Bongani Mawethu Mayosi, FESC (Cape Town, South Africa)
View Discussant report

Read the press release
Open the Presentation
Watch the Webcast

List of Authors:
Bongani M Mayosi, Mpiko Ntsekhe, Jackie Bosch, Shaheen Pandie, Veronica Francis, Laura Joldersma, Freedom Gumedze, Hyejung Jung, Janice Pogue, Salim Yusuf for The IMPI Trial Investigators

Abstract

STUDY OUTLINE
The Investigation of the Management of Pericarditis (IMPI) trial was a multicenter randomized double-blind placebo-controlled 2 × 2 factorial study. Eligible patients are randomly assigned to receive oral prednisolone or placebo for 6 weeks and Mycobacterium indicus pranii injection or placebo for 3 months. The primary outcome was the first occurrence of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. The secondary outcome was safety of immunomodulatory treatment measured by effect on opportunistic infections and malignancy and impact on measures of immunosuppression and the incidence of immune reconstitution disease.
BACKGROUND
Tuberculous (TB) pericarditis affects a million individuals in Africa and the morbidity and mortality are very high despite anti-TB therapy. We evaluated the effectiveness and safety of adjunctive corticosteroids and Mycobacterium indicus pranii in patients with tuberculous pericarditis treated with anti-TB drugs, especially in those with concomitant human immunodeficiency virus (HIV) infection.
METHODS
We randomized 1,400 people (mean age, 38.7 years) with definite or probable tuberculous pericardial effusion to receive adjunctive prednisolone for 6 weeks or placebo, and to receive Mycobacterium indicus pranii immunotherapy or placebo for 3 months with the use of a 2-by-2 factorial design. The primary outcome was a composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. The secondary safety outcomes were the occurrence of opportunistic infection and malignancy (in all patients), and immunosuppression measured by CD4+ T cell count and immune reconstitution disease (in HIV positive patients).
RESULTS
In the prednisolone comparison, the median follow-up was 636.5 days (interquartile range, 317.5 to 1085.5 days); at study end, the primary-outcome status was known for 1371 participants (97.9%). In the Mycobacterium indicus pranii comparison, the median follow-up was 720.5 days (interquartile range, 368.0 to 1095.0); at study end, the primary-outcome status was known for 1223 participants (97.8%). There was no significant difference between prednisolone and placebo (23.8% vs. 24.8%; hazard ratio, 0.95; 95% confidence interval [CI], 0.77 to 1.18; P=0.66), or between Mycobacterium indicus pranii immunotherapy and placebo (25.0% vs. 24.3%; hazard ratio, 1.03; 95% CI, 0.82 to 1.29; P=0.81) with respect to the primary outcome. Prednisolone was associated with a significant reduction in constrictive pericarditis (4.4% vs. 7.8%; hazard ratio, 0.56; 95% CI, 0.36 to 0.85; P=0.009) and hospitalizations (20.7% vs.  25.2%; hazard ratio, 0.79; 95% CI, 0.63 to 0.99; P=0.04). Prednisolone and Mycobacterium indicus pranii were associated with a significant increase in malignancy (1.8% vs. 0.6%; hazard ratio, 3.27; 95% CI, 1.07 to 10.03; P=0.03; and 1.8% vs 0.5%; hazard ratio, 3.69; 95% CI, 1.03 to 13.24; P=0.03, respectively), mainly due to an increase in HIV-associated malignancies. There was no difference in median CD4+ T cell count during the study and in the occurrence of immune reconstitution disease between the two groups for the two comparisons in HIV infected individuals.
CONCLUSIONS
In patients with tuberculous pericarditis, neither prednisolone nor Mycobacterium indicus pranii had a significant effect on the composite of death, cardiac tamponade or constrictive pericarditis. Both therapies were associated with an increased risk of HIV-associated malignancies. However, use of adjunctive steroids reduced the incidence of pericardial constriction and hospitalization. The beneficial effects of prednisolone on constriction and hospitalization were similar in HIV-positive and HIV-negative patients.

Discussion

By Rick Nishimura (Rochester, United States of America)
See Presenter abstract

Open the presentation
Watch the Webcast

 

References


711

SessionTitle:

Hot Line: Coronary artery disease and atrial fibrillation

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.