Phase 4 trial of miltefosine for the treatment of Indian visceral leishmaniasis.
BACKGROUND
Visceral leishmaniasis (VL) is a major public health problem in Bihar, accounting for 90% of all cases in India. Development of high levels of resistance to various existing drugs necessitated the search for alternative orally administered drugs. Hospital-based studies have shown that oral miltefosine is a highly effective treatment for VL both in adults and in children.


METHODS
An open, single-arm trial was designed to investigate the feasibility of treatment of VL patients with miltefosine in field conditions in 13 centers in Bihar.


RESULTS
The phase 4 study was conducted among 1132 adult and pediatric VL patients. Compliance was good, with 1084 (95.5%) patients completing the full 28-day treatment course. Nine hundred and seventy-one (85.8%) patients returned for the final cure assessment at 6 months after treatment. The final cure rate was 82% by intention to treat analysis and 95% by per protocol analysis (similar to the 94% cure rate in hospitalized patients). Treatment-related adverse events of common toxicity criteria grade 3 occurred in ~3% of patients, including gastrointestinal toxicity and rise in aspertate amino transferase, alanine amino transferase, or serum creatinine levels, similar to previous clinical experience.


CONCLUSIONS
This study supports the use of miltefosine in an outpatient setting in an area where VL is endemic.
Bhattacharya
Sujit Kumar
SK
Rajendra Memorial Research Institute of Medical Sciences, Agam-Kuan, India. sujitkbhattacharya@yahoo.com
Sinha
Prabhat Kumar
PK
Sundar
Shyam
S
Thakur
Chandreshar Prasad
CP
Jha
Tara Kant
TK
Pandey
Krishna
K
Das
Vidyanand Rabi
VR
Kumar
Naveen
N
Lal
Chandrasekhar
C
Verma
Neena
N
Singh
Vijay Pratap
VP
Ranjan
Alok
A
Verma
Rakesh Bihari
RB
Anders
Gerlind
G
Sindermann
Herbert
H
Ganguly
Nirmal Kumar
NK
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D002214:Capsules / Q000008:administration & dosage; D056486:Chemical and Drug Induced Liver Injury; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D007194:India; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008107:Liver Diseases / Q000097:blood; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
D000981:Antiprotozoal Agents; D002214:Capsules; D010767:Phosphorylcholine; C039128:miltefosine; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase