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Duality%20of%20interests

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Title: Diastolic Dysfunction in the Population Author: Mike Anderson Last modified by: Bongani Mayosi Created Date: 3/29/1999 7:53:04 PM Document presentation format – PowerPoint PPT presentation

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Title: Duality%20of%20interests


1
Duality of interests
  • B.M. Mayosi has received research grants from
    AstraZeneca, Cadila Pharma, Novartis, Pfizer,
    Roche, and Servier

2
Background
  • Tuberculous (TB) pericarditis affects up to a
    million people per year worldwide.
  • The case fatality rate associated with
    tuberculous pericarditis is as high as 40
    despite anti-tuberculosis treatment.
  • The use of adjunctive corticosteroids may reduce
    the inflammatory response to tuberculosis and
    reduce morbidity (i.e., cardiac tamponade and
    constrictive pericarditis) and mortality
    associated with the disease.
  • There is also evidence that immunotherapy with
    Mycobacterium indicus pranii, a non-pathogenic
    environmental organism, may reduce inflammation
    associated with pulmonary TB.
  • However, there is uncertainty about the safety
    and effectiveness of adjunctive steroids and
    Mycobacterium indicus pranii in TB pericarditis

3
IMPI Primary Objective
The primary objective of the Investigation of the
Management of Pericarditis (IMPI) Trial was to
assess the safety and effectiveness of oral
prednisolone and Mycobacterium indicus pranii
immunotherapy in reducing the composite outcome
of death, cardiac tamponade requiring
pericardiocentesis, or constrictive pericarditis
in patients with definite or probable tuberculous
pericardial effusion.
4
IMPI Study Design
  • Randomized double-blind placebo-controlled 2x2
    factorial multi-centre and multi-national trial
  • Enrol 1400 patients with definite or probable TB
    pericardial effusion over 36 months, and follow
    the last patient enrolled for 6 months
  • Eligible patients were randomly assigned to
    receive oral prednisolone or placebo for 6 weeks
    and Mycobacterium indicus pranii injection or
    placebo for 3 months
  • Patients were followed at weeks 2, 4, 6, and
    months 3 and 6, six-monthly follow-up was
    performed thereafter for up to four years.

5
IMPI Trial Interventions
  • Prednisolone and placebo were supplied as
    identical tablets (5mg, 30mg and 40mg) 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.
  • Patients enrolled in the Mycobacterium indicus
    pranii received 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 received a similar regimen of placebo
    injections of normal saline in identically
    packaged vials.

6
IMPI Organization
19 Centers in Africa
African Coordinating Center University of Cape
Town, South Africa
International Coordinating Center Population
Health Research Institute HHS and McMaster
University, Hamilton, Canada
Sponsors Canadian Institutes for Health
Research, Cadila Pharma, South African Medical
Research Council, Lily and Ernst Hausmann Trust
7
IMPI Target Population
  • Inclusion Criteria
  • Age 18 years
  • Confirmed pericardial effusion on
    echocardiography
  • Evidence of definite or probable TB
    pericarditis (Mayosi BM et al. Circulation 2005)
  • Within 1 week of starting of anti-TB treatment
  • Informed consent
  • Exclusion Criteria
  • Presence of an alternative cause of
    pericardial disease
  • Pregnancy
  • Use of corticosteroids within the previous
    month
  • Hypersensitivity or allergy to the
    Mycobacterium indicus pranii

8
IMPI Prednisolone Selected Baseline
Characteristics
Characteristics Prednisolone Placebo
N 706 694
Age (SD) 38.8 (13.5) 38.5 (13.3)
Female (n, ) 317 (44.9) 299 (43.1)
HIV positive (n, ) 474 (67.1) 465 (67.0)
Centesis done (n, ) 428 (60.6) 419 (60.4)
Definite TB (n, ) 189 (26.7) 185 (26.7)
Probable TB pericarditis 506 (71.7) 506 (72.9)
Non-TB cause (n, ) 11 (1.5) 3 (0.4)
On anti-retrovirals (n, ) 99 (14.0) 104 (15.0)
9
IMPI Mycobacterium Selected Baseline
Characteristics
Characteristics M. Indicus pranii Placebo
N 625 625
Age (SD) 37.7 (12.5) 39.3 (14.1)
Female (n, ) 292 (46.7) 263 (42.1)
HIV positive (n, ) 437 (69.9) 403 (64.5)
Centesis done (n, ) 372 (59.5) 381(61.0)
Definite TB (n, ) 167 (26.7) 158 (25.3)
Probable TB pericarditis 450 (72.0) 462 (73.9)
Non-TB cause (n, ) 8 (1.3) 5 (0.8)
On anti-retrovirals (n, ) 88 (14.1) 84 (13.4)
10
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11
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12
IMPI Time To Primary Outcome
13
IMPI Prednisolone Time To Constriction
14
IMPI Prednisolone Hospitalization
15
IMPI Time To Malignancy
16
IMPI Prednisolone Sub-group analysis
17
IMPI Prednisolone Sub-group analysis
18
IMPI Conclusions
  • In those with definite or probable TB pericardial
    effusion
  • Adjunctive therapy with prednisolone for 6 weeks
    and Mycobacterium indicus pranii for three months
    did not have a significant effect on the combined
    outcome of death from all causes, cardiac
    tamponade requiring pericardiocentesis or
    constrictive pericarditis.
  • Both therapies were associated with an increased
    risk of HIV-associated malignancies.
  • However, use of adjunctive steroids reduced the
    incidence of pericardial constriction and
    hospitalization.
  • The beneficial effects of prednisolone on
    constriction and hospitalization were similar in
    HIV-positive and HIV-negative patients.
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