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

Am Heart J. 2013 Feb;165(2):109-15.e3. doi: 10.1016/j.ahj.2012.08.006. Epub 2012 Dec 13.

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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Pericardial Effusion / surgery*
  • Pericardiocentesis / methods*
  • Pericarditis, Tuberculous / complications
  • Pericarditis, Tuberculous / drug therapy*
  • Pericarditis, Tuberculous / surgery
  • Pilot Projects
  • Prednisolone / administration & dosage*
  • Prospective Studies
  • Treatment Outcome

Substances

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