Injectable paromomycin for Visceral leishmaniasis in India

N Engl J Med. 2007 Jun 21;356(25):2571-81. doi: 10.1056/NEJMoa066536.


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. ( number, NCT00216346.)

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amphotericin B / adverse effects
  • Amphotericin B / therapeutic use
  • Animals
  • Antiprotozoal Agents / administration & dosage
  • Antiprotozoal Agents / adverse effects
  • Antiprotozoal Agents / therapeutic use*
  • Audiometry
  • Child
  • Child, Preschool
  • Disease Reservoirs
  • Female
  • Hearing Disorders / chemically induced
  • Hearing Disorders / diagnosis
  • Humans
  • India
  • Infusions, Intravenous
  • Injections, Intramuscular
  • Kidney Diseases / chemically induced
  • Leishmania donovani*
  • Leishmaniasis, Visceral / drug therapy*
  • Leishmaniasis, Visceral / mortality
  • Male
  • Middle Aged
  • Paromomycin / administration & dosage
  • Paromomycin / adverse effects
  • Paromomycin / therapeutic use*
  • Prospective Studies
  • Treatment Outcome


  • Antiprotozoal Agents
  • Paromomycin
  • Amphotericin B

Associated data