Prednisolone and Mycobacterium indicus pranii in tuberculous pericarditis.

BACKGROUND: Tuberculous pericarditis is associated with high morbidity and mortality even if antituberculosis therapy is administered. We evaluated the effects of adjunctive glucocorticoid therapy and Mycobacterium indicus pranii immunotherapy in patients with tuberculous pericarditis. METHODS: Using a 2-by-2 factorial design, we randomly assigned 1400 adults with definite or probable tuberculous pericarditis to either prednisolone or placebo for 6 weeks and to either M. indicus pranii or placebo, administered in five injections over the course of 3 months. Two thirds of the participants had concomitant human immunodeficiency virus (HIV) infection. The primary efficacy outcome was a composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. RESULTS: There was no significant difference in the primary outcome between patients who received prednisolone and those who received placebo (23.8% and 24.5%, respectively; hazard ratio, 0.95; 95% confidence interval [CI], 0.77 to 1.18; P=0.66) or between those who received M. indicus pranii immunotherapy and those who received placebo (25.0% and 24.3%, respectively; hazard ratio, 1.03; 95% CI, 0.82 to 1.29; P=0.81). Prednisolone therapy, as compared with placebo, was associated with significant reductions in the incidence of constrictive pericarditis (4.4% vs. 7.8%; hazard ratio, 0.56; 95% CI, 0.36 to 0.87; P=0.009) and hospitalization (20.7% vs. 25.2%; hazard ratio, 0.79; 95% CI, 0.63 to 0.99; P=0.04). Both prednisolone and M. indicus pranii, each as compared with placebo, were associated with a significant increase in the incidence of cancer (1.8% vs. 0.6%; hazard ratio, 3.27; 95% CI, 1.07 to 10.03; P=0.03, and 1.8% vs. 0.5%; hazard ratio, 3.69; 95% CI, 1.03 to 13.24; P=0.03, respectively), owing mainly to an increase in HIV-associated cancer. CONCLUSIONS: In patients with tuberculous pericarditis, neither prednisolone nor M. indicus pranii had a significant effect on the composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. (Funded by the Canadian Institutes of Health Research and others; IMPI ClinicalTrials.gov number, NCT00810849.).

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. 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.

STELLIUM 1: First-in-man follow-up evaluation of bioabsorbable polymer-coated paclitaxel-eluting stent.

BACKGROUND: Durable polymers used for first-generation drug-eluting stents (DES) potentially contribute to persistent inflammation and late DES thrombosis. The vascular response to the Stellium stent, which is coated with an absorbable polymer for slow release of low-dose paclitaxel, was evaluated in the present study. METHODS AND RESULTS: The 37 patients with stable angina were implanted with 47 Stellium stents. Quantitative coronary angiography (QCA) was performed at baseline, and QCA and optical coherence tomography (OCT) were performed at 6 months post-implant. The primary endpoint was major adverse cardiac events (MACE). At 6 months, 1 case of MACE occurred because of total occlusion of a protected left main artery. In-stent and segment binary restenosis rates were both 0%. In-stent late loss was 0.19 ± 0.54 mm. Altogether, 5,564 struts were visualized by OCT and mean neointimal thickness was 150.03 ± 146.36 µm. The number of well-apposed struts with and without neointima overlay was 5,135 (92.29%) and 396 (7.12%), respectively. Peri-strut low intensity was observed in 518 struts (9.31%). CONCLUSIONS: This first-in-man study of the Stellium stent shows the promising possibility of bioabsorbable polymeric surface coating paclitaxel-eluting stents out to 6 months. The low rate of peri-strut low intensity suggests low cellular toxicity of the Stellium stent compared with the first-generation DES.

Clinical characteristics and initial management of patients with tuberculous pericarditis in the HIV era: the Investigation of the Management of Pericarditis in Africa (IMPI Africa) registry.

BACKGROUND: The incidence of tuberculous pericarditis has increased in Africa as a result of the human immunodeficiency virus (HIV) epidemic. However, the effect of HIV co-infection on clinical features and prognosis in tuberculous pericarditis is not well characterised. We have used baseline data of the Investigation of the Management of Pericarditis in Africa (IMPI Africa) registry to assess the impact of HIV co-infection on clinical presentation, diagnostic evaluation, and treatment of patients with suspected tuberculous pericarditis in sub-Saharan Africa. METHODS: Consecutive adult patients in 15 hospitals in three countries in sub-Saharan Africa were recruited on commencement of treatment for tuberculous pericarditis, following informed consent. We recorded demographic, clinical, diagnostic and therapeutic information at baseline, and have used the chi-square test and analysis of variance to assess probabilities of significant differences (in these variables) between groups defined by HIV status. RESULTS: A total of 185 patients were enrolled from 01 March 2004 to 31 October 2004, 147 (79.5%) of whom had effusive, 28 (15.1%) effusive-constrictive, and 10 (5.4%) constrictive or acute dry pericarditis. Seventy-four (40%) had clinical features of HIV infection. Patients with clinical HIV disease were more likely to present with dyspnoea (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.4 to 7.4, P = 0.005) and electrocardiographic features of myopericarditis (OR 2.8, 95% CI 1.1 to 6.9, P = 0.03). In addition to electrocardiographic features of myopericarditis, a positive HIV serological status was associated with greater cardiomegaly (OR 3.89, 95% CI 1.34 to 11.32, P = 0.01) and haemodynamic instability (OR 9.68, 95% CI 2.09 to 44.80, P = 0.0008). However, stage of pericardial disease at diagnosis and use of diagnostic tests were not related to clinical HIV status. Similar results were obtained for serological HIV status. Most patients were treated on clinical grounds, with microbiological evidence of tuberculosis obtained in only 13 (7.0%) patients. Adjunctive corticosteroids were used in 109 (58.9%) patients, with patients having clinical HIV disease less likely to be put on them (OR 0.37, 95% CI 0.20 to 0.68). Seven patients were on antiretroviral drugs. CONCLUSION: Patients with suspected tuberculous pericarditis and HIV infection in Africa have greater evidence of myopericarditis, dyspnoea, and haemodynamic instability. These findings, if confirmed in other studies, may suggest more intensive management of the cardiac disease is warranted in patients with HIV-associated pericardial disease.

Mortality in patients treated for tuberculous pericarditis in sub-Saharan Africa.

OBJECTIVE: To determine the mortality rate and its predictors in patients with a presumptive diagnosis of tuberculous pericarditis in sub-Saharan Africa. DESIGN: Between 1 March 2004 and 31 October 2004, we enrolled 185 consecutive patients with presumed tuberculous pericarditis from 15 referral hospitals in Cameroon, Nigeria and South Africa, and observed them during the 6-month course of antituberculosis treatment for the major outcome of mortality. This was an observational study, with the diagnosis and management of each patient left at the discretion of the attending physician. Using Cox regression, we have assessed the effect of clinical and therapeutic characteristics (recorded at baseline) on mortality during follow-up. RESULTS: We obtained the vital status of 174 (94%) patients (median age 33; range 14 - 87 years). The overall mortality rate was 26%. Mortality was higher in patients who had clinical features of HIV infection than in those who did not (40% v. 17%, p=0.001). Independent predictors of death during followup were: (i) a proven non-tuberculosis final diagnosis (hazard ratio (HR) 5.35, 95% confidence interval (CI) 1.76 - 16.25), (ii) the presence of clinical signs of HIV infection (HR 2.28, CI 1.14 - 4.56), (iii) coexistent pulmonary tuberculosis (HR 2.33, CI 1.20 - 4.54), and (iv) older age (HR 1.02, CI 1.01 - 1.05). There was also a trend towards an increase in death rate in patients with haemodynamic instability (HR 1.80, CI 0.90 - 3.58) and a decrease in those who underwent pericardiocentesis (HR 0.34, CI 0.10 - 1.19). CONCLUSION: A presumptive diagnosis of tuberculous pericarditis is associated with a high mortality in sub-Saharan Africa. Attention to rapid aetiological diagnosis of pericardial effusion and treatment of concomitant HIV infection may reduce the high mortality associated with the disease.