title: Efficacy and safety of amphotericin B emulsion versus liposomal formulation in Indian patients with visceral leishmaniasis: a randomized, open-label study.
abstract: BACKGROUND
  India is home to 60% of the total global visceral leishmaniasis (VL) population. Use of long-term oral (e.g. miltefosine) and parenteral drugs, considered the mainstay for treatment of VL, is now faced with increased resistance, decreased efficacy, low compliance and safety issues. The authors evaluated the efficacy and safety of an alternate treatment option, i.e. single infusion of preformed amphotericin B (AmB) lipid emulsion (ABLE) in comparison with that of liposomal formulation (LAmB).
  
  
  METHODS
  In this multicentric, open-label study, 500 patients with VL were randomly assigned in a 3:1 ratio to receive 15 mg/kg single infusion of either ABLE (N = 376) or LAmB (N = 124). Initial cure (Day 30/45), clinical improvement (Day 30) and long term definitive cure (Day 180) were assessed.
  
  
  RESULTS
  A total of 326 (86.7%) patients in the ABLE group and 122 (98.4%) patients in the LAmB group completed the study. Initial cure was achieved by 95.9% of patients in the ABLE group compared to 100% in the LAmB group (p = 0.028; 95% CI: -0.0663, -0.0150). Clinical improvement was comparable between treatments (ABLE: 98.9% vs. LAmB: 98.4%). Definitive cure was achieved in 85.9% with ABLE compared to 98.4% with LAmB. Infusion-related pyrexia (37.2% vs. 32.3%) and chills (18.4% vs. 18.5%) were comparable between ABLE and LAmB, respectively. Treatment-related serious adverse events were fewer in ABLE (0.3%) compared to LAmB (1.6%). Two deaths occurred in the ABLE group, of which one was probably related to the study drug. Nephrotoxicity and hepatotoxicity was not observed in either group.
  
  
  CONCLUSIONS
  ABLE 15 mg/kg single infusion had favorable efficacy and was well tolerated. Considering the demographic profile of the population in this region, a single dose treatment offers advantages in terms of compliance, cost and applicability.
  
  
  BACKGROUND
  www.clinicaltrials.gov NCT00876824.
authors.affiliation: Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
authors.forename: Shyam
authors.initials: S
authors.lastname: Sundar
authors.affiliation: Department of Clinical Medicine, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Agamkuan, Patna, Bihar, India.
authors.forename: Krishna
authors.initials: K
authors.lastname: Pandey
authors.affiliation: Balaji Utthan Sansthan, Kala-azar Research Centre, Patna, Bihar, India.
authors.forename: Chandreshwar Prasad
authors.initials: CP
authors.lastname: Thakur
authors.affiliation: Kalazar Research Centre, Brahmpura, Muzaffarpur, Bihar, India.
authors.forename: Tara Kant
authors.initials: TK
authors.lastname: Jha
authors.affiliation: Department of Clinical Medicine, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Agamkuan, Patna, Bihar, India.
authors.forename: Vidya Nand Ravi
authors.initials: VN
authors.lastname: Das
authors.affiliation: Department of Pathology, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Agamkuan, Patna, Bihar, India.
authors.forename: Neena
authors.initials: N
authors.lastname: Verma
authors.affiliation: Department of Biochemistry, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Agamkuan, Patna, Bihar, India.
authors.forename: Chandra Shekhar
authors.initials: CS
authors.lastname: Lal
authors.affiliation: Kala-azar Medical Research Center, Muzaffarpur, Bihar, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Verma
authors.affiliation: Kala-azar Medical Research Center, Muzaffarpur, Bihar, India.
authors.forename: Shahnawaz
authors.initials: S
authors.lastname: Alam
authors.affiliation: Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Agamkuan, Patna, Bihar, India.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Das
mesh_terms: D000293:Adolescent; D000328:Adult; D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004655:Emulsions; D005260:Female; D005334:Fever / Q000188:drug therapy; D006801:Humans; D007194:India / Q000453:epidemiology; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D012756:Sheep; D055815:Young Adult
chemical_list: D000981:Antiprotozoal Agents; D004655:Emulsions; C068538:liposomal amphotericin B; D000666:Amphotericin B