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Previous Volume 356:2571-2581 June 21, 2007 Number 25 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set CME Exam Perspective by Klempner, M. S. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background Visceral leishmaniasis (kala-azar) affects large, rural, resource-poor populations in South Asia, Africa, and Brazil. Safe, effective, and affordable new therapies are needed. We conducted a randomized, controlled, phase 3 open-label study comparing paromomycin, an aminoglycoside, with amphotericin B, the present standard of care in Bihar, India.

Methods In four treatment centers for visceral leishmaniasis, 667 patients between 5 and 55 years of age who were negative for the human immunodeficiency virus and had parasitologically confirmed visceral leishmaniasis were randomly assigned in a 3:1 ratio to receive paromomycin (502 patients) at a dose of 11 mg per kilogram of body weight intramuscularly daily for 21 days or amphotericin B (165 patients) at a dose of 1 mg per kilogram intravenously every other day for 30 days. Final cure was assessed 6 months after the end of treatment; safety assessments included daily clinical evaluations and weekly laboratory and audiometric evaluations. Noninferiority testing was used to compare 6-month cure rates, with a chosen margin of noninferiority of 10 percentage points.

Results Paromomycin was shown to be noninferior to amphotericin B (final cure rate, 94.6% vs. 98.8%; difference, 4.2 percentage points; upper bound of the 97.5% confidence interval, 6.9; P<0.001). Mortality rates in the two groups were less than 1%. Adverse events, which were more common among patients receiving paromomycin than among those receiving amphotericin B (6% vs. 2%, P=0.02), included transient elevation of aspartate aminotransferase levels (>3 times the upper limit of the normal range); transient reversible ototoxicity (2% vs. 0, P=0.20); and injection-site pain (55% vs. 0, P<0.001); and in patients receiving amphotericin B, as compared with those receiving paromomycin, nephrotoxicity (4% vs. 0, P<0.001), fevers (57% vs. 3%), rigors (24% vs. 0, P<0.001), and vomiting (10% vs. <1%, P<0.001).

Conclusions Paromomycin was shown to be noninferior to amphotericin B for the treatment of visceral leishmaniasis in India. (ClinicalTrials.gov number, NCT00216346 [ClinicalTrials.gov] .)

Source Information

From the Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh (S.S.); the Kala-azar Research Centre, Brahmpura, Muzaffarpur, Bihar (T.K.J.); Balaji Utthan Sansthan, Patna, Bihar (C.P.T.); and the Rajendra Memorial Research Institute of Medical Sciences, Patna, Bihar (P.K.S., S.K.B.) — all in India.

Address reprint requests to Dr. Sundar at the Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India, or at drshyamsundar{at}hotmail.com.

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