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BARCELONA -- Adding steroids to anti-tuberculosis treatment for patients with tuberculous pericarditis can reduce the risk of an important complication and the resulting hospital admissions, researchers said here.

But in a large randomized trial, adding prednisolone to tuberculosis (TB) treatment did not reduce the risk of death, according to of the University of Cape Town in South Africa, and colleagues.

And for patients with HIV -- a majority of trial participants -- the therapy was associated with about a threefold increase in the risk of malignancy, Mayosi reported at the European Society of Cardiology meeting.

Study results were published simultaneously in the

Tuberculous pericarditis "is the most important and the most serious form of pericardial disease in the world," Mayosi said, occurring in about 10% of the 10 million new TB patients every year.

Earlier research had suggested that steroids could reduce the mortality of the disease, which is about 26% by 6 months after diagnosis, and even higher in patients with AIDS.

The bottom line of the Investigation of the Management of Pericarditis trial was that "we need to be selective in the use of steroids," Mayosi said, because despite some benefits, there remains the risk of cancers in people with concomitant HIV.

Much of the disease burden of tuberculous pericarditis is in developing countries, where many TB patients are also co-infected with HIV, Mayosi noted.

The study also investigated the effect of injections of a nonpathogenic bacterium, heat-killed , also known as Mycobacterium w, which had been hypothesized to reduce the inflammation associated with TB.

But that part of the study was stopped early because of futility, he reported.

The investigators used a factorial design to investigate the effects of the two substances on a composite endpoint of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis.

Some 1,400 patients with probably or confirmed tuberculous pericarditis were randomly assigned to get prednisolone or placebo for 6 weeks. Within each group they were re-randomized to get five injections of M. indicus pranii or placebo over 3 months.

The researchers also looked at the elements of the composite endpoint separately as secondary efficacy endpoints, as well as such things as opportunistic infections, hospital admissions, and the occurrence of new malignancies to judge safety.

For the steroid/placebo comparison, Mayosi reported, there was no significant difference in the primary outcome: 23.8% of those getting prednisolone and 24.5% on placebo reached that endpoint.

In particular, when the investigators looked at the separate elements, there was no significant difference in mortality -- 18.8% of those getting the steroid died from any cause compared with 16.6% of those on placebo.

The risk of cardiac tamponade was also not significantly different, with 3.1% of those on the steroid and 4.0% of those on placebo having the complication.

On the other hand, 4.4% of those getting prednisolone had constrictive pericarditis, compared with 7.8% of placebo patients, yielding a hazard ratio of 0.56 that was significant (P=0.009).

Hospital admissions were 20.7% versus 25.2% for prednisolone and placebo patients, respectively, leading to an HR of 0.79 (P=0.04).

The difference was mainly driven by constrictive pericarditis, Mayosi said.

For the other comparison -- M. indicus pranii or placebo -- there was no significant difference either in the composite endpoint or the separate components, he reported.

On the other hand, both interventions were associated with a significant increase in the risk of malignancy compared with placebo:

• The incidence of new cancers was 1.8% for prednisolone versus 0.6% for placebo (HR 3.27, 95% CI 1.07-10.03, P=0.03)
• For the mycobacterium and placebo, the rates were 1.8% and 0.5%, respectively (HR 3.69, 95% CI 1.03-13.24, P=0.03)

The increase in HIV-related cancer with prednisolone therapy was mainly due to Kaposi's sarcoma and non-Hodgkins lymphoma, Mayosi said.

The reduction in constrictive pericarditis and hospital admission with prednisolone treatment is "clinically meaningful," commented , and , both of the Johns Hopkins University School of Medicine.

In an, they said, "subgroup analyses to determine which patients benefited most will be informative."

But HIV-positive patients have a clearly greater risk of cancer, suggesting the "use of glucocorticoids should be curtailed in this population unless the risk of constrictive pericarditis is high," Chaisson and Post argued.

On the other hand, the lack of benefit from M. indicus pranii is no surprise, they added, "since the scientific rationale for this therapy in patients with tuberculous pericarditis is underwhelming."