Trial record 14 of 26 for:    Open Studies | "Leishmaniasis"

Phase III, Study of Three Short Course Combination Regimens (Ambisome®, Miltefosine, Paromomycin) Compared With AmBisome® Alone for the Treatment of Visceral Leishmaniasis in Bangladesh

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2011 by Drugs for Neglected Diseases.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Shaheed Surhawardy Medical College and Hospital
International Centre for Diarrhoeal Disease Research, Bangladesh
Information provided by:
Drugs for Neglected Diseases
ClinicalTrials.gov Identifier:
NCT01122771
First received: May 11, 2010
Last updated: July 1, 2011
Last verified: July 2011
  Purpose

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.


Condition Intervention Phase
Visceral Leishmaniasis
Drug: Liposomal amphotericin B
Drug: liposomal amphotericin B + miltefosine
Drug: liposomal amphotericin B + paromomycin
Drug: Miltefosine + Paromomycin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III, Open Label, Randomised, Study of Three Short Course Combination Regimens (Ambisome®, Miltefosine, Paromomycin) Compared With AmBisome® Alone for the Treatment of Visceral Leishmaniasis (VL) in Bangladesh

Resource links provided by NLM:


Further study details as provided by Drugs for Neglected Diseases:

Primary Outcome Measures:
  • Definitive cure [ Time Frame: 6 month post treatment ] [ Designated as safety issue: No ]

    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.


Secondary Outcome Measures:
  • Initial Cure [ Time Frame: Day 45 ] [ Designated as safety issue: No ]

    Initial Cure is defined as no significant clinical signs or symptoms of VL at Day 45 ie lack of fever [axiliary temp < 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

  • Adverse events [ Time Frame: Treatment ] [ Designated as safety issue: Yes ]

    Assess safety during treatment and follow-up in different healthcare settings

    • in hospital setting based on clinical adverse events, laboratory parameters during treatment and 6 months follow-up
    • In UZHC setting based on clinical adverse events, limited laboratory parameters during treatment and 6 months follow-up


Estimated Enrollment: 674
Study Start Date: May 2010
Estimated Study Completion Date: July 2012
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ambisome
15mg Ambisome on days 1,3 and 5
Drug: Liposomal amphotericin B
Ambisome i.v. 5mg on days 1, 3 and 5
Other Name: AmBisome
Experimental: Ambisome + Miltefosine
Ambisome 5mg + miltefosine 10 days
Drug: liposomal amphotericin B + miltefosine
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)
Other Names:
  • Impavido
  • AmBisome
Experimental: Ambisome +paromomycin
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
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 Name: Impavido
Experimental: Miltefosine + paromomycin
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
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 Name: Impavido

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.

  Eligibility

Ages Eligible for Study:   5 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01122771

Contacts
Contact: Ridwanur Rahman, MD ridwanurr@yahoo.com
Contact: kazi Jamil, MD jamil@icddrb.org

Locations
Bangladesh
Bhaluka UZHC Not yet recruiting
Bhaluka, Mymensingh, Bangladesh
Gaffargaon Recruiting
Gaffargaon, Mymensingh, Bangladesh
Community Based Medical College Active, not recruiting
Trishal, Mymensingh, Bangladesh
Trishal UZHC Not yet recruiting
Trishal, Mymensingh, Bangladesh
Sponsors and Collaborators
Drugs for Neglected Diseases
Shaheed Surhawardy Medical College and Hospital
International Centre for Diarrhoeal Disease Research, Bangladesh
Investigators
Principal Investigator: Ridwanur Rahman, MD Shaheed Surawardy Medical College
  More Information

No publications provided

Responsible Party: Prof R Rahman, Shaheed Surhawardy Medical College and Hospital
ClinicalTrials.gov Identifier: NCT01122771     History of Changes
Other Study ID Numbers: VLCombo-BD-09
Study First Received: May 11, 2010
Last Updated: July 1, 2011
Health Authority: Bangladesh Medical research council, Bangladesh:
ICDDR,B Ethics Committee, Bangladesh:
Ministry of Health, Bangladesh:

Keywords provided by Drugs for Neglected Diseases:
visceral leishmaniasis
phase III
randomised ccontrolled trial
Bangladesh
Combination treatment
Ambisome
miltefosine
paromomycin

Additional relevant MeSH terms:
Leishmaniasis
Leishmaniasis, Visceral
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases
Skin Diseases, Parasitic
Skin Diseases, Infectious
Skin Diseases
Amphotericin B
Paromomycin
Liposomal amphotericin B
Miltefosine
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Bacterial Agents
Antifungal Agents
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 18, 2014