Clinical Trial: A Trial of Adjunctive Prednisolone and Mycobacterium w Immunotherapy in Tuberculous Pericarditis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Trial of Adjunctive Prednisolone and Mycobacterium w Immunotherapy in Tuberculous Pericarditis

Brief Summary: Human immunodeficiency virus (HIV) infection puts people at risk of opportunistic infections, such as tuberculosis. In Africa, the HIV epidemic has resulted in an increase in the number of cases of tuberculosis affecting various parts of the body, including the membrane surrounding the heart (i.e., pericardium). Pericardial tuberculosis is a serious form of tuberculosis that results in the death or disability of 1 in 2 affected people despite the use of antituberculosis medication. It has been suggested that the addition of corticosteroids to the antituberculosis medication could result in the reduction of the number of deaths caused by the disease, but this proposal remains to be confirmed in appropriately designed clinical trials. Similarly, vaccination with the Mycobacterium w injection is also proposed as a possible way of reducing the damage caused by the tuberculosis infection of the heart. The investigators are proposing to conduct a clinical trial in which people who are on antituberculosis treatment for pericardial tuberculosis will be randomly allocated to receive either prednisolone or a matching placebo tablet, or Mycobacterium w injection or placebo injection. The number of people who die or who develop hardening of the pericardium with compression of the heart (called pericardial constriction) or who need emergency evacuation of the pericardial fluid from pericardial sac for severe compression (called tamponade) will be compared in each group to determine whether the use of corticosteroids or Mycobacterium w injection is safe and results in reduction in the death rate. If corticosteroids and Mycobacterium w are shown to safely reduce the death rate, then they will be recommended for use in all patients with tuberculosis of the pericardium in the future.

Detailed Summary:

Summary of research proposal Tuberculous pericarditis is one of the most severe forms of infection with Mycobacterium tuberculosis, causing death or cardiac disability in nearly half of those affected in spite of antituberculosis chemotherapy. Attenuation of the inflammatory response in tuberculous pericarditis may improve outcome by reducing the likelihood of cardiac tamponade and pericardial constriction. A meta-analysis of all randomized controlled trials of corticosteroids for tuberculous pericarditis showed a trend towards reduction of mortality, but the studies were too small to confirm any effect on survival. Concern remains that corticosteroids might increase the frequency of opportunistic infections and cancers in patients infected with the Human Immunodeficiency Virus (HIV). In addition to the promising but inconclusive evidence on adjunctive steroids, there is preliminary evidence suggesting that repeated doses of Mycobacterium w immunotherapy may reduce the inflammation associated with extrapulmonary tuberculosis and increase the CD4 cell count in people infected with HIV. These early observations remain to be tested in a large randomized trial with the hard endpoint of mortality.

The Investigation of the Management of Pericarditis in Africa (IMPI [pronounced as 'ee-mp-ee', for Zulu warriors]) Trial will assess effectiveness and safety of oral prednisolone or placebo and Mycobacterium w immunotherapy or placebo in 1400 patients with tuberculous pericardial effusion. This trial will also determine the feasibility of conducting a large-scale multicentre clinical trial in patients with tuberculous pericarditis in sub-Saharan Africa.

Hypothesis: We hypothesize that patients with suspected tuberculous pericarditis randomized to adjunctive oral prednisolone for 6 weeks will have a 30% reduction in mortality compared
Sponsor: University of Cape Town

Current Primary Outcome: Composite end-point of death, constriction, or cardiac tamponade requiring pericardial drainage. [ Time Frame: Two years ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Safety of immunomodulatory treatment [ Time Frame: Two years ]
  • The secondary efficacy outcomes are the individual components of the composite primary outcome (i.e., death, constriction, and cardiac tamponade requiring pericardiocentesis), and all-cause hospitalization. [ Time Frame: 2 years ]


Original Secondary Outcome:

  • Safety of immunomodulatory treatment [ Time Frame: Two years ]
  • Long-term feasibility of conducting a multi-centre trial in Africa and India [ Time Frame: 2 years ]


Information By: University of Cape Town

Dates:
Date Received: December 17, 2008
Date Started: December 2008
Date Completion:
Last Updated: September 2, 2014
Last Verified: September 2014