Effectiveness Study of Paromomycin IM Injection (PMIM) for the Treatment of Visceral Leishmaniasis (VL) in Bangladesh.
BACKGROUND
This study was conducted in Bangladeshi patients in an outpatient setting to support registration of Paromomycin Intramuscular Injection (PMIM) as a low-cost treatment option in Bangladesh.


METHODS
This Phase IIIb, open-label, multi-center, single-arm trial assessed the efficacy and safety of PMIM administered at 11 mg/kg (paromomycin base) intramuscularly once daily for 21 consecutive days to children and adults with VL in a rural outpatient setting in Bangladesh. Patients ≥5 and ≤55 years were eligible if they had signs and symptoms of VL (intermittent fever, weight loss/decreased appetite, and enlarged spleen), positive rK39 test, and were living in VL-endemic areas. Compliance was the percentage of enrolled patients who received 21 daily injections over no more than 22 days. Efficacy was evaluated by initial clinical response, defined as resolution of fever and reduction of splenomegaly at end of treatment, and final clinical response, defined as the absence of new clinical signs and symptoms of VL 6 months after end of treatment. Safety was assessed by evaluation of adverse events.


RESULTS
A total of 120 subjects (49% pediatric) were enrolled. Treatment compliance was 98.3%. Initial clinical response in the Intent-to-Treat population was 98.3%, and final clinical response 6 months after end of treatment was 94.2%. Of the 119 subjects who received ≥1 dose of PMIM, 28.6% reported at least one adverse event. Injection site pain was the most commonly reported adverse event. Reversible renal impairment and/or hearing loss were reported in 2 subjects.


CONCLUSIONS
PMIM was an effective and safe treatment for VL in Bangladesh. The short treatment duration and lower cost of PMIM compared with other treatment options may make this drug a preferred treatment to be investigated as part of a combination therapy regimen. This study supports the registration of PMIM for use in government health facilities in Bangladesh.


BACKGROUND
ClinicalTrials.gov identifier: NCT01328457.
Kuwait Institute for Scientific Research, Environment and Life Sciences Research Center, Food and Nutrition Program, formerly International Center for Diarrheal Disease Research, Bangladesh (icddr,b), Mohakhali, Dhaka, Bangladesh.
Kazi M
KM
Jamil
International Center for Diarrheal Disease Research, Bangladesh (icddr,b), Mohakhali, Dhaka, Bangladesh.
Rashidul
R
Haque
Shaheed Suhrawardy Medical College Hospital (SSMCH), Sher-E-Bangla Nagor, Dhaka, Bangladesh.
Ridwanur
R
Rahman
Dev Care Foundation, Dhaka, Bangladesh and Retired Ministry of Health, Government of Bangladesh Official.
M Abul
MA
Faiz
International Center for Diarrheal Disease Research, Bangladesh (icddr,b), Mohakhali, Dhaka, Bangladesh.
Abu Toha Md Rezwanul Haque
AT
Bhuiyan
PATH, formerly OneWorld Health.
Amresh
A
Kumar
PATH, formerly OneWorld Health.
Syed Misbah
SM
Hassan
PATH, formerly OneWorld Health.
Heather
H
Kelly
International AIDS Vaccine Initiative, formerly OneWorld Health.
Pritu
P
Dhalaria
John Snow India, formerly OneWorld Health.
Sonali
S
Kochhar
PATH, formerly OneWorld Health.
Philippe
P
Desjeux
International Center for Diarrheal Disease Research, Bangladesh (icddr,b), Mohakhali, Dhaka, Bangladesh.
Mohammad A A
MA
Bhuiyan
International Center for Diarrheal Disease Research, Bangladesh (icddr,b), Mohakhali, Dhaka, Bangladesh.
Mohammed M
MM
Khan
Bill & Melinda Gates Foundation, formerly PATH.
Raj Shankar
RS
Ghosh
D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D001459:Bangladesh; D002648:Child; D002675:Child, Preschool; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D017048:Health Care Costs; D006801:Humans; D007273:Injections, Intramuscular; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010303:Paromomycin / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D016896:Treatment Outcome; D055815:Young Adult
D000890:Anti-Infective Agents; D010303:Paromomycin