Rationale and design of the Investigation of the Management of Pericarditis (IMPI) trial: a 2 × 2 factorial randomized double-blind multicenter trial of adjunctive prednisolone and Mycobacterium w immunotherapy in tuberculous pericarditis.

Abstract

BACKGROUND:

In spite of antituberculosis chemotherapy, tuberculous (TB) pericarditis causes death or disability in nearly half of those affected. Attenuation of the inflammatory response in TB pericarditis may improve outcome by reducing cardiac tamponade and pericardial constriction, but there is uncertainty as to whether adjunctive immunomodulation with corticosteroids and Mycobacterium w (M. w) can safely reduce mortality and morbidity.

OBJECTIVES:

The primary objective of the IMPI Trial is to assess the effectiveness and safety of prednisolone and M. w immunotherapy in reducing the composite outcome of death, constriction, or cardiac tamponade requiring pericardial drainage in 1,400 patients with TB pericardial effusion.

DESIGN:

The IMPI trial is a multicenter international randomized double-blind placebo-controlled 2 × 2 factorial study. Eligible patients are randomly assigned to receive oral prednisolone or placebo for 6 weeks and M. w injection or placebo for 3 months. Patients are followed up at weeks 2, 4, and 6 and months 3 and 6 during the intervention period and 6-monthly thereafter for up to 4 years. The primary outcome is the first occurrence of death, pericardial constriction, or cardiac tamponade requiring pericardiocentesis. The secondary outcome is safety of immunomodulatory treatment measured by effect on opportunistic infections (eg, herpes zoster) and malignancy (eg, Kaposi sarcoma) and impact on measures of immunosuppression and the incidence of immune reconstitution disease.

CONCLUSIONS:

IMPI is the largest trial yet conducted comparing adjunctive immunotherapy in pericarditis. Its results will define the role of adjunctive corticosteroids and M. w immunotherapy in patients with TB pericardial effusion.

• Authors: Bongani M Mayosi, Mpiko Ntsekhe, Jackie Bosch, Janice Pogue, Freedom Gumedze, Motasim Badri, Hyejung Jung, Shaheen Pandie, Marek Smieja, Lehana Thabane, Veronica Francis, Kandithal M Thomas, Baby Thomas, Abolade A Awotedu, Nombulelo P Magula, Datshana P Naidoo, Albertino Damasceno, Alfred Chitsa Banda, Arthur Mutyaba, Basil Brown, Patrick Ntuli, Phindile Mntla, Lucas Ntyintyane, Rohan Ramjee, Pravin Manga, Bruce Kirenga, Charles Mondo, James B W Russell, Jacob M Tsitsi, Ferande Peters, Mohammed R Essop, Ayub Felix Barasa, Muhammad S Mijinyawa, Mahmoud U Sani, Taiwo Olunuga, Okechukwu Ogah, Adewole Adebiyi, Akinyemi Aje, Victor Ansa, Dike Ojji, Solomon Danbauchi, James Hakim, Jonathan Matenga, Salim Yusuf
• Journal: American heart journal (Am Heart J) Vol. 165 Issue 2 Pg. 109-15.e3 (Feb 2013) ISSN: 1097-6744 [Electronic] United States
• PMID: 23351812 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Mosby, Inc. All rights reserved.

Chemical References

• Adrenal Cortex Hormones
• Antitubercular Agents
• Bacterial Vaccines
• Mycobacterium w vaccine
• Prednisolone

Topics

• Adrenal Cortex Hormones (therapeutic use)
• Aged
• Antitubercular Agents (therapeutic use)
• Bacterial Vaccines (therapeutic use)
• Double-Blind Method
• Female
• Follow-Up Studies
• Humans
• Immunotherapy (methods)
• Male
• Middle Aged
• Mycobacterium (immunology)
• Pericardial Effusion (etiology, surgery)
• Pericardiocentesis (methods)
• Pericarditis, Tuberculous (complications, drug therapy, surgery)
• Pilot Projects
• Prednisolone (administration & dosage)
• Prospective Studies
• Treatment Outcome