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.
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.


OBJECTIVE
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.


METHODS
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.
The Cardiac Clinic, Department of Medicine, Groote Schuur Hospital, Cape Town, South Africa. bongani.mayosi@uct.ac.za
Bongani M
BM
Mayosi
Mpiko
M
Ntsekhe
Jackie
J
Bosch
Janice
J
Pogue
Freedom
F
Gumedze
Motasim
M
Badri
Hyejung
H
Jung
Shaheen
S
Pandie
Marek
M
Smieja
Lehana
L
Thabane
Veronica
V
Francis
Kandithal M
KM
Thomas
Baby
B
Thomas
Abolade A
AA
Awotedu
Nombulelo P
NP
Magula
Datshana P
DP
Naidoo
Albertino
A
Damasceno
Alfred Chitsa
AC
Banda
Arthur
A
Mutyaba
Basil
B
Brown
Patrick
P
Ntuli
Phindile
P
Mntla
Lucas
L
Ntyintyane
Rohan
R
Ramjee
Pravin
P
Manga
Bruce
B
Kirenga
Charles
C
Mondo
James B W
JB
Russell
Jacob M
JM
Tsitsi
Ferande
F
Peters
Mohammed R
MR
Essop
Ayub Felix
AF
Barasa
Muhammad S
MS
Mijinyawa
Mahmoud U
MU
Sani
Taiwo
T
Olunuga
Okechukwu
O
Ogah
Adewole
A
Adebiyi
Akinyemi
A
Aje
Victor
V
Ansa
Dike
D
Ojji
Solomon
S
Danbauchi
James
J
Hakim
Jonathan
J
Matenga
Salim
S
Yusuf
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000368:Aged; D000995:Antitubercular Agents / Q000627:therapeutic use; D001428:Bacterial Vaccines / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009161:Mycobacterium / Q000276:immunology*; D010490:Pericardial Effusion / Q000209:etiology / Q000601:surgery*; D020519:Pericardiocentesis / Q000379:methods*; D010495:Pericarditis, Tuberculous / Q000150:complications / Q000188:drug therapy* / Q000601:surgery; D010865:Pilot Projects; D011239:Prednisolone / Q000008:administration & dosage*; D011446:Prospective Studies; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000995:Antitubercular Agents; D001428:Bacterial Vaccines; C080550:Mycobacterium w vaccine; D011239:Prednisolone