Safety and Efficacy Study to Evaluate Different Combination Treatment Regimens for Visceral Leishmaniasis
Condition: Visceral Leishmaniasis
MeSH terms: Leishmaniasis; Leishmaniasis, Visceral
Study type: Interventional
Phase: Phase 3

Summary: 
      The overall objective of this trial is to identify a safe and effective combination,
      (coadministration) short course treatment for the treatment of visceral leishmaniasis which
      could be easily deployed in a control programme and will reduce the risk of parasite
      resistance occurring.

      Safety and tolerability should be such that the combination can be easily deployed.
    

Detailed description: 
      New, effective, less toxic and simplified treatments are urgently needed to replace or
      complement the few currently available drugs to treat visceral Leishmaniasis. An interim
      strategy and one which will slow the emergence of resistant parasite strains is to use
      coadministration of currently available drugs.

      In India, first line treatment is now amphotericin B which is administered as an intravenous
      infusion, on alternate days over a 4 week period. A liposomal formulation of amphotericin B,
      AmBisome, is also available, and is substantially less nephrotoxic than amphotericin B, but
      is expensive.

      It is acknowledged that AmBisome is the most effective therapy for visceral leishmaniasis,
      but it's high cost has hampered implementation. Use as part of a combination treatment,
      potentially as a single, lower dose, could reduce treatment costs considerably and thereby
      increase access for patients.

      Two new treatments have recently been licensed in India for the treatment of patients with
      VL,

        -  Paromomycin administered as an intramuscular injection, once daily for 21 days

        -  Miltefosine administered as an oral tablet, once daily for 28 days. These drugs are now
           being used as monotherapy with high risk of emergence of resistant parasites. With price
           reduction for AmBisome, preferential pricing for Miltefosine and the concern for
           emergence of resistant parasites due to monotherapy, it is time to move rapidly toward
           obtaining definitive data for making recommendations on combination therapy as soon as
           possible, before these valuable drugs become useless. The present protocol will be a
           definitive Phase-III trial with the aim that at the end of this trial, strong
           evidence-based recommendations on combination therapy with available drugs can be made
           to Authorities in the Indian sub-continent. This protocol will evaluate various
           combinations of the three drugs; AmBisome, Paromomycin and Miltefosine at reduced total
           dosage and in shorter courses, against the present standard treatment with amphotericin
           B deoxycholate.
    

Intervention name(s): Amphotericin B Deoxycholate; Ambisome + Miltefosine; Ambisome and Paromomycin; Miltefosine and Paromomycin
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 1 mg/kg e.o.d for 30 days; Ambisome (i.v. single dose 5 mg/kg)+ Miltefosine 7 days; Ambisome 5 mg/kg single dose + Paromomycin Sulphate 15mg/kg/day for 10 days; Miltefosine (standard dose) and Paromomycin Sulphate 15mg/kg/day for 10 days
Intervention MeSH terms: Amphotericin B; Paromomycin; Liposomal amphotericin B; Miltefosine; Amphotericin B, deoxycholate drug combination; Deoxycholic Acid
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment