Rifapentine no better than rifampin for intensive phase treatment of pulmonary TB
Using rifapentine instead of rifampin during intensive phase treatment of pulmonary tuberculosis (TB) does not seem to offer a significant advantage.
Rifapentine (Priftin) is approved in the U.S. for treating active TB in a dose of 600 mg (approximately 10 mg/kg) given once or twice a week in combination with other anti-TB drugs.
In mice, giving rifapentine five days a week rather than once or twice achieves durable cures without relapse after only three months -- but until now there were no data on the safety and antimicrobial activity of a five-days-a-week rifapentine regimen in humans.
At 24 hospitals around the world, Dr. Susan E. Dorman from Johns Hopkins University in Baltimore, Maryland and colleagues in the Tuberculosis Trials Consortium randomly assigned 531 adults to receive either rifampin (10 mg/kg) or rifapentine (10 mg/kg) five days a week during the first eight weeks (intensive phase) of combination treatment for pulmonary tuberculosis.
Everyone also received isoniazid, pyrazinamide, and ethambutol, the authors reported online July 30 in The Journal of Infectious Diseases.
Like other researchers before them, this group used sputum culture status at completion of eight weeks of treatment as their surrogate endpoint for efficacy, even though, as they admit, "it has imperfect specificity and sensitivity as a predictor of the 'gold standard' clinical outcomes of treatment failure and relapse."
In a per protocol analysis, there was no significant difference in the percentage of negative liquid cultures at the end of the intensive phase with rifampin vs rifapentine (65.1% vs 67.9%; p=0.65). Results were similar for solid cultures.
Post hoc analyses found similar results for patients with noncavitary and cavitary pulmonary tuberculosis.
Women and patients with more doses of prestudy TB medications were more likely than others to achieve negative sputum cultures at the end of the intensive phase.
Factors independently associated with failure to achieve negative sputum culture included increasing age, cigarette use, high bacillary burden on smear microscopy, fever, and productive cough.
Similar numbers of patients discontinued their assigned treatment due to toxicity, and similar numbers of patients in each treatment group developed hepatitis.
"Rifapentine remains a promising drug with potential for tuberculosis treatment shortening," the investigators conclude, "and recent work by Dooley and colleagues indicates that higher rifapentine daily doses appear to be safe and tolerable in healthy volunteers."
They add, "To continue to evaluate the potential for rifapentine to support shorter-course therapy for drug-susceptible tuberculosis, assessment of safety, activity, and pharmacokinetics of higher daily rifapentine doses in patients with active tuberculosis is warranted."
Dr. Dorman did not respond to a request for comments.
SOURCE: http://bit.ly/NsimBc
J Infect Dis 2012.
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