Amphotericin B treatment for Indian visceral leishmaniasis: response to 15 daily versus alternate-day infusions.
BACKGROUND
For patients with Indian visceral leishmaniasis, amphotericin B deoxycholate is usually given as 15 alternate-day infusions of 1 mg/kg over 30 days (total dose, 15 mg/kg); daily treatment with 1 mg/kg for 20 days (total dose, 20 mg/kg) is also used. This study was done to address the unsettled therapeutic questions of administration schedule (alternate-day vs. daily administration) and dose (1 vs. 0.75 mg/kg) and to determine whether the duration of amphotericin B treatment in Bihar, India, can be shortened to 15 days.


METHODS
To compare alternate-day versus daily administration and 1-mg/kg versus 0.75-mg/kg doses and to determine whether the duration of treatment could be abbreviated, Indian subjects randomly received 15 infusions of 1 mg/kg (group A; 245 patients) or 0.75 mg/kg (group B; 244 patients) on alternate days or 1 mg/kg (group C; 500 patients) or 0.75 mg/kg (group D; 496 patients) daily. Noninferiority testing compared 6-month cure rates using a 5% margin.


RESULTS
Overall, 1439 of the 1485 subjects completed treatment and responded. Treatment interruptions (nephrotoxicity) but not infusion-associated reactions or study removals were more common with daily administration. Final cure rates at 6 months were similar: group A, 234 patients (96%; 95% confidence interval [CI], 92%-98%); group B, 225 patients (92%; 95% CI, 88%-95%); group C, 483 patients (97%; 95% CI, 95%-98%); and group D, 476 patients (96%; 95% CI, 94%-97%; P>.05).


CONCLUSIONS
Provided that the serum creatinine level is repeated once, daily treatment with amphotericin B, 0.75 mg/kg for 15 days (total dose, 11.25 mg/kg), is efficient and effective for visceral leishmaniasis in India.


BACKGROUND
ClinicalTrials.gov identifier: NCT00310505.
Sundar
Shyam
S
Kala-Azar Medical Research Center, Department of Medicine, Banaras Hindu University, Institute of Medical Sciences, Varanasi, India. drshyamsundar@hotmail.com
Chakravarty
J
J
Rai
V K
VK
Agrawal
N
N
Singh
S P
SP
Chauhan
V
V
Murray
Henry W
HW
D000293:Adolescent; D000328:Adult; D000666:Amphotericin B / Q000008:administration & dosage*; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007194:India; D007262:Infusions, Intravenous; D007893:Leishmania donovani; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008297:Male; D016896:Treatment Outcome
D000981:Antiprotozoal Agents; D000666:Amphotericin B