Safety and Efficacy Study to Evaluate Different Combination Treatment Regimens for Visceral Leishmaniasis
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.
|Visceral Leishmaniasis||Drug: Amphotericin B Deoxycholate Drug: Ambisome + Miltefosine Drug: Ambisome and Paromomycin Drug: Miltefosine and Paromomycin||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Randomized, Open-label, Parallel-group, Safety & Efficacy Study to Evaluate Different Combination Treatment Regimens, of Either AmBisome and Paromomycin, AmBisome and Miltefosine, or Paromomycin and Miltefosine Compared With Amphotericin B Deoxycholate (the Standard) Therapy for the Treatment of Acute, Symptomatic Visceral Leishmaniasis (VL).|
- Definitive cure based on parasitological clearance at Day 15 after start of combination therapy (Day 31 for standard therapy), no evidence of parasites at day 45 and no clinical signs or symptoms of VL at 6 months post treatment. [ Time Frame: 6 months post treatment ]
|Study Start Date:||June 2008|
|Study Completion Date:||January 2010|
|Primary Completion Date:||January 2010 (Final data collection date for primary outcome measure)|
|Active Comparator: 1||
Drug: Amphotericin B Deoxycholate
1 mg/kg e.o.d for 30 days
Drug: Ambisome + Miltefosine
Ambisome (i.v. single dose 5 mg/kg)+ Miltefosine 7 days
Drug: Ambisome and Paromomycin
Ambisome 5 mg/kg single dose + Paromomycin Sulphate 15mg/kg/day for 10 days
Drug: Miltefosine and Paromomycin
Miltefosine (standard dose) and Paromomycin Sulphate 15mg/kg/day for 10 days
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00696969
|Kala-azar medical centre|
|Muzaffarpur, Bihar, India|
|Rajendra Memorial research Institute|
|Patna, Bihar, India|
|Study Director:||Farrokh Modabber||Drugs for Neglected Diseases|