Combination Therapy in Indian Visceral Leishmaniasis

This study has been completed.
Sponsor:
Collaborators:
Drugs for Neglected Diseases
Rajendra Memorial Research Institute of Medical Sciences
Information provided by:
Banaras Hindu University
ClinicalTrials.gov Identifier:
NCT00523965
First received: August 31, 2007
Last updated: May 25, 2010
Last verified: January 2009

August 31, 2007
May 25, 2010
September 2007
August 2009   (final data collection date for primary outcome measure)
  • Final cure at six month follow up [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
  • Cure at six month follow up [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Final cure at six month follow up [ Time Frame: 18 months ]
Complete list of historical versions of study NCT00523965 on ClinicalTrials.gov Archive Site
Initial cure at the end of treatment [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Initial cure at the end of treatment [ Time Frame: 12 months ]
Not Provided
Not Provided
 
Combination Therapy in Indian Visceral Leishmaniasis
A Randomised, Open-label, Parallel-group, Safety and Efficacy Study to Evaluate Different Combination Treatment Regimens (Co-administration), of AmBisome, Paromomycin and Miltefosine in Visceral Leishmaniasis (VL)

Rationale

The overall objective of this trial is to identify a safe and effective combination, (co-administration) short course treatment for the treatment of VL which could be easily deployed in a control programme. The hypothesis is that the combination treatment is as effective or better than the 5 mg/kg single dose of AmBisome and will reduce the risk of parasite resistance occurring. Safety and tolerability should be such that the combination can be easily deployed.

Objective

The specific primary and secondary objectives are as follows:

Primary objective:

To identify a short course combination treatment regimen which is at least as effective as a single dose of AmBisome 5mg/kg

Secondary objective:

To compare safety and tolerability of the various treatments measured by vital signs, blood biochemistry, (renal and liver function tests) haematology, spontaneous and elicited adverse event reporting

Primary Endpoint:

The primary efficacy endpoint variable is parasitological clearance 2 weeks after start of treatment with no relapse during follow up and no clinical signs or symptoms of VL at 6 months post treatment.

Parasitology is only carried out at any time during follow-up or at six months post treatment if there are signs or symptoms of VL infection.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Leishmaniasis, Visceral
  • Drug: amphotericin B deoxycholate
    Amphotericin B deoxycholate 1 mg/kg on alternate days for 15 infusions
  • Drug: Liposomal Amphotericin B with Miltefosine
    Liposomal Amphotericin B 5 mg Miltefosine 50 mg twice daily if patient weighs equal to or > 25 kg Miltefosine 50 mg once daily if patient weighs <25 mg
  • Drug: Liposomal Amphotericin B and Paromomycin Sulfate
    AmBisome 5mg/kg iv infusion over 2 h x 1 day (single dose) + paromomycin sulfate 15 mg/kg/day i.m for 10 days, on day 2-11
  • Drug: miltefosine + Paromomycin sulfate
    oral miltefosine 50mg once daily (< 25 kg body weight) or twice daily ( > 25 kg body weight) or 2.5 mg/kg for children under 12 years, for 10 days + Paromomycin sulfate 15 mg/kg/day im. for 10 days
  • Experimental: A
    AmBisome 5 mg/kg iv infusion over 2 h x 1 day (single dose) + oral miltefosine 50mg once daily (< 25 kg body weight) or twice daily ( > 25 kg body weight) or 2.5 mg/kg for children under 12 years, for 7 days on day 2-8
    Intervention: Drug: Liposomal Amphotericin B with Miltefosine
  • Experimental: B
    AmBisome 5mg/kg iv infusion over 2 h x 1 day (single dose) + paromomycin sulfate 15 mg/kg/day i.m for 10 days, on day 2-11
    Intervention: Drug: Liposomal Amphotericin B and Paromomycin Sulfate
  • Experimental: C
    oral miltefosine 50mg once daily (< 25 kg body weight) or twice daily ( > 25 kg body weight) or 2.5 mg/kg for children under 12 years, for 10 days + Paromomycin sulfate 15 mg/kg/day im. for 10 days
    Intervention: Drug: miltefosine + Paromomycin sulfate
  • Active Comparator: D
    amphotericin B deoxycholate at 1 mg/kg every other day for 15 infusions
    Intervention: Drug: amphotericin B deoxycholate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
624
February 2010
August 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients > 5 years old with symptoms and signs of kala-azar (fever, weight loss, splenomegaly) and parasites demonstrated by microscopy in splenic aspirate smear

Exclusion Criteria:

  • Pregnant or breast-feeding women
  • Individuals seropositive to HIV or individuals with a serious concurrent infection such as tuberculosis or bacterial pneumonia.
  • Women of child-bearing age will be counseled about adequate birth control during and for three months after miltefosine treatment and provided with a satisfactory method of contra-ception.
  • Granulocyte count < 1,000/mm3, hemoglobin < 5 g/dL or platelet count < 40,000/mm3
  • Hepatic transaminases or total bilirubin greater than three times normal
  • Serum creatinine > 2.0 mg/dL
  • Prothrombin time > 5 seconds above control
  • Inability of subject or guardian to provide written informed consent
Both
12 Years to 60 Years
No
Contact information is only displayed when the study is recruiting subjects
India
 
NCT00523965
VLCombo 07
Yes
Shyam Sundar, Drugs for Neglected Diseases Initiative
Banaras Hindu University
  • Drugs for Neglected Diseases
  • Rajendra Memorial Research Institute of Medical Sciences
Principal Investigator: Shyam Sundar, MD Institute of Medical Sciences, Banaras HIndu University
Principal Investigator: P K Sinha, MD Rajendra Memorial Research Insititute of Medical Sciences
Banaras Hindu University
January 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP