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

NCT00810849 | Completed Phase 3 DMC

• 1 other identifier: IMPI-TRIAL1
• Study Type: interventional
• Target: 1,400
• Locations: 1 country
• Sites: 1

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.

Conditions

Tuberculous Pericarditis

Keywords

Tuberculosis, pericardium

Outcome Measures

Primary Outcomes (1)

• Composite end-point of death, constriction, or cardiac tamponade requiring pericardial drainage.

  Two years

Secondary Outcomes (2)

• Safety of immunomodulatory treatment

  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.

  2 years

Study Arms (2)

Prednisolone

PLACEBO COMPARATOR

Six-week tapering course of prednisolone and those assigned to the prednisolone control arm will receive the same number of identically-coated placebo tablets.

Drug: Prednisolone

Mycobacterium w

PLACEBO COMPARATOR

Patients enrolled in the Mycobacterium w experimental arm will receive 5 doses of 0.1 ml of the vaccine intradermally (on enrolment, at 2 weeks, 4 weeks, 6 weeks, and 3 months).

Biological: Mycobacterium w immunotherapy

Interventions

Prednisolone DRUG

Prednisolone and placebo will be supplied as 5 mg identical tablets and given at a dosage of 120 mg/day in the first week, followed by 90 mg/day in the second week, 60 mg/day in the third week, 30 mg/day in the fourth week, 15 mg/day in the fifth week, and 5 mg/day in the sixth week.

Also known as: Medrol tablets

Prednisolone

Mycobacterium w immunotherapy BIOLOGICAL

Patients enrolled in the Mycobacterium w experimental arm will receive 5 doses of 0.1 ml of the vaccine intradermally (on enrolment, at 2 weeks, 4 weeks, 6 weeks, and 3 months). Patients in the control arm of the Mycobacterium w comparison will receive a similar regime of placebo injections of normal saline in identically-packaged vials.

Also known as: Immuvac

Mycobacterium w

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients admitted with suspected tuberculous pericarditis will be eligible if they meet all three of the following criteria:
• A confirmed pericardial effusion on echocardiography;
• Evidence of definite or probable tuberculous pericarditis; and
• Within 1 week of starting of antituberculosis treatment.

You may not qualify if:

• Presence of an alternative cause of pericardial disease, e.g., penetrating chest trauma in the previous 12 months and malignancy.
• Use of corticosteroids within the previous month.
• Hypersensitivity or allergy to the Mycobacterium w vaccine.
• Pregnancy.
• Age \< 18 years.

Sponsors & Collaborators

• University of Cape Town: lead
• Population Health Research Institute: collaborator

Study Sites (1)

Groote Schuur Hospital

Cape Town, Western Cape, 7925, South Africa

Location

Related Publications (2)

• Mayosi BM, Ntsekhe M, Bosch J, Pogue J, Gumedze F, Badri M, Jung H, Pandie S, Smieja M, Thabane L, Francis V, Thomas KM, Thomas B, Awotedu AA, Magula NP, Naidoo DP, Damasceno A, Banda AC, Mutyaba A, Brown B, Ntuli P, Mntla P, Ntyintyane L, Ramjee R, Manga P, Kirenga B, Mondo C, Russell JB, Tsitsi JM, Peters F, Essop MR, Barasa AF, Mijinyawa MS, Sani MU, Olunuga T, Ogah O, Adebiyi A, Aje A, Ansa V, Ojji D, Danbauchi S, Hakim J, Matenga J, Yusuf S. Rationale and design of the Investigation of the Management of Pericarditis (IMPI) trial: a 2 x 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.

  PMID: 23351812 BACKGROUND

• Mayosi BM, Ntsekhe M, Bosch J, Pandie S, Jung H, Gumedze F, Pogue J, Thabane L, Smieja M, Francis V, Joldersma L, Thomas KM, Thomas B, Awotedu AA, Magula NP, Naidoo DP, Damasceno A, Chitsa Banda A, Brown B, Manga P, Kirenga B, Mondo C, Mntla P, Tsitsi JM, Peters F, Essop MR, Russell JB, Hakim J, Matenga J, Barasa AF, Sani MU, Olunuga T, Ogah O, Ansa V, Aje A, Danbauchi S, Ojji D, Yusuf S; IMPI Trial Investigators. Prednisolone and Mycobacterium indicus pranii in tuberculous pericarditis. N Engl J Med. 2014 Sep 18;371(12):1121-30. doi: 10.1056/NEJMoa1407380. Epub 2014 Sep 1.

  PMID: 25178809 DERIVED

MeSH Terms

Conditions

Pericarditis, Tuberculous

Interventions

Prednisolone; Methylprednisolone; Immuvac

Condition Hierarchy (Ancestors)

Tuberculosis, Cardiovascular; Tuberculosis, Extrapulmonary; Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Cardiovascular Infections; Cardiovascular Diseases; Pericarditis; Heart Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Salim Yusuf, M.D.

  Population Health Research Institute, McMaster University, Hamilton, Canada

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: December 17, 2008
• First Posted: December 18, 2008
• Study Start: December 1, 2008
• Primary Completion: February 1, 2014
• Study Completion: August 1, 2014
• Last Updated: September 3, 2014

Record last verified: 2014-09

Locations

ZA (1)