Single-dose liposomal amphotericin B for visceral leishmaniasis in India.
BACKGROUND
Some 50% of patients with visceral leishmaniasis (kala-azar) worldwide live in the Indian state of Bihar. Liposomal amphotericin B is an effective treatment when administered in short courses. We wanted to determine whether the efficacy of a single infusion of liposomal amphotericin B was inferior to conventional parenteral therapy, consisting of 15 alternate-day infusions of amphotericin B deoxycholate.


METHODS
In this open-label study, we randomly assigned 412 patients in a 3:1 ratio to receive either liposomal amphotericin B (liposomal-therapy group) or amphotericin B deoxycholate (conventional-therapy group). Liposomal amphotericin B (at a dose of 10 mg per kilogram of body weight) was given once, and patients were discharged home 24 hours later. Amphotericin B deoxycholate, which was administered in 15 infusions of 1 mg per kilogram, was given every other day during a 29-day hospitalization. We determined the cure rate 6 months after treatment.


RESULTS
A total of 410 patients--304 of 304 patients (100%) in the liposomal-therapy group and 106 of 108 patients (98%) in the conventional-therapy group--had apparent cure responses at day 30. Cure rates at 6 months were similar in the two groups: 95.7% (95% confidence interval [CI], 93.4 to 97.9) in the liposomal-therapy group and 96.3% (95% CI, 92.6 to 99.9) in the conventional-therapy group. Adverse events in the liposomal-therapy group were infusion-related fever or rigors (in 40%) and increased anemia or thrombocytopenia (in 2%); such events in the conventional-therapy group were fever or rigors (in 64%), increased anemia (in 19%), and hypokalemia (in 2%). Nephrotoxicity or hepatotoxicity developed in no more than 1% of patients in each group.


CONCLUSIONS
A single infusion of liposomal amphotericin B was not inferior to and was less expensive than conventional therapy with amphotericin B deoxycholate. (ClinicalTrials.gov number, NCT00628719.)
Sundar
Shyam
S
Kala-Azar Medical Research Center, Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. drshyamsundar@hotmail.com
Chakravarty
Jaya
J
Agarwal
Dipti
D
Rai
Madhukar
M
Murray
Henry W
HW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D002648:Child; D002675:Child, Preschool; D003840:Deoxycholic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007194:India; D007262:Infusions, Intravenous; D057194:Intention to Treat Analysis; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D000981:Antiprotozoal Agents; D004338:Drug Combinations; C068538:liposomal amphotericin B; D003840:Deoxycholic Acid; D000666:Amphotericin B; C059765:amphotericin B, deoxycholate drug combination