Prednisolone and Mycobacterium indicus pranii in tuberculous pericarditis.

Abstract

BACKGROUND:

Tuberculous pericarditis is associated with high morbidity and mortality even if antituberculosis therapy is administered. We evaluated the effects of adjunctive glucocorticoid therapy and Mycobacterium indicus pranii immunotherapy in patients with tuberculous pericarditis.

METHODS:

Using a 2-by-2 factorial design, we randomly assigned 1400 adults with definite or probable tuberculous pericarditis to either prednisolone or placebo for 6 weeks and to either M. indicus pranii or placebo, administered in five injections over the course of 3 months. Two thirds of the participants had concomitant human immunodeficiency virus (HIV) infection. The primary efficacy outcome was a composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis.

RESULTS:

There was no significant difference in the primary outcome between patients who received prednisolone and those who received placebo (23.8% and 24.5%, respectively; hazard ratio, 0.95; 95% confidence interval [CI], 0.77 to 1.18; P=0.66) or between those who received M. indicus pranii immunotherapy and those who received placebo (25.0% and 24.3%, respectively; hazard ratio, 1.03; 95% CI, 0.82 to 1.29; P=0.81). Prednisolone therapy, as compared with placebo, was associated with significant reductions in the incidence of constrictive pericarditis (4.4% vs. 7.8%; hazard ratio, 0.56; 95% CI, 0.36 to 0.87; P=0.009) and hospitalization (20.7% vs. 25.2%; hazard ratio, 0.79; 95% CI, 0.63 to 0.99; P=0.04). Both prednisolone and M. indicus pranii, each as compared with placebo, were associated with a significant increase in the incidence of cancer (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), owing mainly to an increase in HIV-associated cancer.

CONCLUSIONS:

In patients with tuberculous pericarditis, neither prednisolone nor M. indicus pranii had a significant effect on the composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. (Funded by the Canadian Institutes of Health Research and others; IMPI ClinicalTrials.gov number, NCT00810849.).

• Authors: Bongani M Mayosi, Mpiko Ntsekhe, Jackie Bosch, Shaheen Pandie, Hyejung Jung, Freedom Gumedze, Janice Pogue, Lehana Thabane, Marek Smieja, Veronica Francis, Laura Joldersma, Kandithalal M Thomas, Baby Thomas, Abolade A Awotedu, Nombulelo P Magula, Datshana P Naidoo, Albertino Damasceno, Alfred Chitsa Banda, Basil Brown, Pravin Manga, Bruce Kirenga, Charles Mondo, Phindile Mntla, Jacob M Tsitsi, Ferande Peters, Mohammed R Essop, James B W Russell, James Hakim, Jonathan Matenga, Ayub F Barasa, Mahmoud U Sani, Taiwo Olunuga, Okechukwu Ogah, Victor Ansa, Akinyemi Aje, Solomon Danbauchi, Dike Ojji, Salim Yusuf, IMPI Trial Investigators
• Journal: The New England journal of medicine (N Engl J Med) Vol. 371 Issue 12 Pg. 1121-30 (Sep 18 2014) ISSN: 1533-4406 [Electronic] United States
• PMID: 25178809 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Glucocorticoids
• Prednisolone

Topics

• Adult
• Cardiac Tamponade (etiology, prevention & control)
• Combined Modality Therapy
• Female
• Glucocorticoids (adverse effects, therapeutic use)
• HIV Infections (complications)
• Humans
• Immunotherapy
• Kaplan-Meier Estimate
• Male
• Mycobacterium (immunology)
• Pericardiocentesis
• Pericarditis, Constrictive (etiology, prevention & control)
• Pericarditis, Tuberculous (complications, drug therapy, mortality)
• Prednisolone (adverse effects, therapeutic use)
• Treatment Failure