NCT01122771

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
602

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started May 2010

Typical duration for phase_3

Geographic Reach
1 country

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2010

Completed
10 days until next milestone

First Submitted

Initial submission to the registry

May 11, 2010

Completed
2 days until next milestone

First Posted

Study publicly available on registry

May 13, 2010

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2014

Completed
Last Updated

January 21, 2016

Status Verified

January 1, 2016

Enrollment Period

3.8 years

First QC Date

May 11, 2010

Last Update Submit

January 20, 2016

Conditions

Visceral Leishmaniasis

Keywords

visceral leishmaniasisphase IIIrandomised ccontrolled trialBangladeshCombination treatmentAmbisomemiltefosineparomomycin

Outcome Measures

Primary Outcomes (1)

  • Definitive cure

    The primary endpoint variable is definitive cure at month 6, and is defined as no significant clinical signs or symptoms of VL at Day 45 including lack of fever \[axiliary temperature \< 99.5°F\] and at least one of the following: * improved Hb if the patient was anaemic at baseline (Hb\< 8g/dl) * spleen regression if the spleen was palpable on admission and absence of clinical signs and symptoms of VL (fever, weight loss, splenomegaly) at any time during 6 months post treatment period.

    6 month post treatment

Secondary Outcomes (2)

  • Initial Cure

    Day 45

  • Adverse events

    Treatment

Study Arms (4)

Ambisome

ACTIVE COMPARATOR

15mg Ambisome on days 1,3 and 5

Drug: Liposomal amphotericin B

Ambisome + Miltefosine

EXPERIMENTAL

Ambisome 5mg + miltefosine 10 days

Drug: liposomal amphotericin B + miltefosine

Ambisome +paromomycin

EXPERIMENTAL

AmBisome IV infusion (single dose, day 1) + Paromomycin base 11mg/kg/day IM (Gland Pharma, India) for 10 days (days 2-11)

Drug: liposomal amphotericin B + paromomycin

Miltefosine + paromomycin

EXPERIMENTAL

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).

Drug: Miltefosine + Paromomycin

Interventions

Liposomal amphotericin BDRUG

Ambisome i.v. 5mg on days 1, 3 and 5

Also known as: AmBisome
Ambisome
liposomal amphotericin B + miltefosineDRUG

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)

Also known as: Impavido, AmBisome
Ambisome + Miltefosine
liposomal amphotericin B + paromomycinDRUG

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).

Also known as: Impavido
Ambisome +paromomycin
Miltefosine + ParomomycinDRUG

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).

Also known as: Impavido
Miltefosine + paromomycin

Eligibility Criteria

Age5 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • VL proven by parasitological examination of splenic or bone marrow aspirate. Parasite burden to be graded according to Chulay and Bryceson 1983 and subsequently adopted by WHO. (Step 1 only)
  • History of fever, for at least 2 weeks with one or more of the followings criteria: Anaemia (5\<Hb\<10g/dl), Loss of weight, Splenomegaly
  • rk39 positive at baseline assessments
  • willing and able to attend follow-up visits
  • Male or Female age: 5-60 yrs
  • Written informed consent from the patient or from patient's parent or guardian if the patient is under 18 yrs, in addition written assent from patients of 11 - 17 yrs of age. If the patient or parent/guardian are illiterate an impartial witness should be present during the consenting procedure and should also sign.

You may not qualify if:

  • Married women of child-bearing potential (defined as women who have achieved menarche) who are not using an assured method of contraception or are unwilling to use an assured method of contraception for the duration of treatment and three months after. Assured methods of contraception include i.e. IUCD or depot hormone injection of medroxyprogesterone acetate MPA (DepoProvera®)
  • Platelet count less than 40,000/mm3 (Step 1 only)
  • Prothrombin time 5 seconds or greater than normal range (Step 1 only)
  • Known hepatitis B, C or known HIV positive
  • Patients who present with Para Kala-azar Dermal Leishmaniasis
  • Signs/symptoms indicative of severe VL (Hb \< 5gm/dl, etc)
  • Patients with a previous history of VL
  • Patients who have received any investigational (unlicensed) drugs within the last 3 months
  • Severe malnutrition BMI\<15 in adults, weight for height less than 60% in children
  • Clinical symptoms of chronic underlying disease such as severe cardiac, renal or hepatic impairment
  • Positive HRP2/pLDH Combo test for malaria
  • Pregnant woman or breast-feeding mother
  • Known alcohol or other drug abuse
  • Concomitant chronic drug treatment eg. TB, HIV etc.
  • Known hypersensitivity to AmBisome, Paromomycin and other aminoglycosides and/or Miltefosine

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Bhaluka UZHC

Bhaluka, Mymensingh, Bangladesh

Location

Gaffargaon

Gafargaon, Mymensingh, Bangladesh

Location

Community Based Medical College

Trishal, Mymensingh, Bangladesh

Location

Trishal UZHC

Trishal, Mymensingh, Bangladesh

Location

Related Publications (1)

  • Rahman R, Goyal V, Haque R, Jamil K, Faiz A, Samad R, Ellis S, Balasegaram M, Boer MD, Rijal S, Strub-Wourgaft N, Alves F, Alvar J, Sharma B. Safety and efficacy of short course combination regimens with AmBisome, miltefosine and paromomycin for the treatment of visceral leishmaniasis (VL) in Bangladesh. PLoS Negl Trop Dis. 2017 May 30;11(5):e0005635. doi: 10.1371/journal.pntd.0005635. eCollection 2017 May.

    PMID: 28558062DERIVED

MeSH Terms

Conditions

Leishmaniasis, Visceral

Interventions

liposomal amphotericin BmiltefosineParomomycin

Condition Hierarchy (Ancestors)

LeishmaniasisEuglenozoa InfectionsProtozoan InfectionsParasitic DiseasesInfectionsVector Borne Diseases

Intervention Hierarchy (Ancestors)

AminoglycosidesGlycosidesCarbohydrates

Study Officials

  • Ridwanur Rahman, MD

    Shaheed Surawardy Medical College

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 11, 2010

First Posted

May 13, 2010

Study Start

May 1, 2010

Primary Completion

March 1, 2014

Study Completion

March 1, 2014

Last Updated

January 21, 2016

Record last verified: 2016-01

Locations

BA(4)