Phase III, Study of Three Short Course Combo (Ambisome®, Miltefosine, Paromomycin) Compared With AmBisome for the Treatment of VL in Bangladesh
Condition: Visceral Leishmaniasis
MeSH terms: Leishmaniasis; Leishmaniasis, Visceral
Study type: Interventional
Phase: Phase 3

Summary: 
      This protocol will evaluate the efficacy and safety of various combinations of the three
      drugs; AmBisome, Paromomycin and Miltefosine at reduced total dosage against the standard
      treatment with a total dose of 15mg/kg of AmBisome.
    

Detailed description: 
      Visceral leishmaniasis (VL) is the most severe form of leishmaniasis. The causative parasite
      in Bangladesh is almost exclusively L. donovani.

      • The current treatment options in Bangladesh are not satisfactory as they are either toxic
      and long, or are of limited use in women of childbearing age due to possible teratogenicity,
      long treatment duration which leads to non-compliance and possible emergence of resistance or
      expensive.

      In collaboration with Indian Medical Research Council and investigators in India, DNDi
      initiated a combination trial for treatment of VL in Bihar, India in 2008 including 624
      patients from age 5 - 60. The same combinations will be used in the present study. An interim
      safety review was conducted on the first 120 patients included in the Indian VL Combination
      study and revealed no safety issues with combination treatment. The enrolment is complete and
      the final results for 624 patients are expected in Q1 2010.

      This is a randomized, controlled, open-label, parallel group study to compare the safety and
      efficacy of different combination regimens with AmBisome for the treatment of VL in
      Bangladesh.

      This trial is designed in two steps:

      Step 1: First 120 patients will be recruited in a hospital setting in a study including
      parasitology and laboratory assessments at Community Based Medical College, Bangladesh
      (CBMC,B), primarily for the purpose of reconfirming the safety of combination treatments in
      Bangladesh. Pending the review and approval of an independent DSMB of the Day 45 data, step 2
      will commence.

      Step 2: Approximately 554 Patients will then be recruited and treated in Upazilla Health
      Centre's (UZHC), situated in endemic regions of Bangladesh. We will use rapid diagnostic test
      (RDT) and the limited laboratory assessments that are available in the centres.

      Female patients will be stratified according to marital status, such that unmarried women of
      child-bearing age will be stratified to receive treatments that do not contain Miltefosine,
      and married women will be stratified to receive one of the four treatment regimens and must
      consent to use an approved method of contraception and undergo pregnancy test at the start of
      the study. Child-bearing age is defined as achieving menarche.

      There will be one planned safety review assessing safety and initial cure at Day 45 following
      completion of Step 1.
    

Intervention name(s): Liposomal amphotericin B; liposomal amphotericin B + miltefosine; liposomal amphotericin B + paromomycin; Miltefosine + Paromomycin
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Ambisome i.v. 5mg on days 1, 3 and 5; Ambisome 5mg single dose iv Oral Miltefosine 1.5-2.5 mg/kg in 1 or 2 doses a day, for 10 days (days 1-10); Oral Miltefosine 1.5-2.5 mg/kg in 1 or 2 doses a day, for 10 days (days 1-10) + Paromomycin base 11mg/kg/day IM for 10 days (days 1-10).; Oral Miltefosine 1.5-2.5 mg/kg in 1 or 2 doses a day, for 10 days (days 1-10) + Paromomycin base 11mg/kg/day IM for 10 days (days 1-10).
Other intervention name(s): AmBisome; Impavido; AmBisome; Impavido; Impavido
Intervention MeSH terms: Amphotericin B; Paromomycin; Liposomal amphotericin B; Miltefosine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: visceral leishmaniasis; phase III; randomised ccontrolled trial; Bangladesh; Combination treatment; Ambisome; miltefosine; paromomycin