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Visceral LeishmaniasisPhase 3NCT01122771

Phase III, Study of Three Short Course Combo (Ambisome®, Miltefosine, Paromomycin) Compared With AmBisome for the Treatment of VL in Bangladesh

A Phase 3 study testing Liposomal amphotericin B, liposomal amphotericin B + miltefosine and liposomal amphotericin B + paromomycin in people with Visceral Leishmaniasis, run by Drugs for Neglected Diseases at 4 sites in Bangladesh.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 5 to 60 years
Conditions the study is for
Visceral Leishmaniasis
What is being tested?
Liposomal amphotericin B, liposomal amphotericin B + miltefosine and liposomal amphotericin B + paromomycin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
602 participants
Where
4 sitesBangladesh
Study dates
May 2010to Mar 2014
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 5 to 60 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.

Who cannot join

  • 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)
Show all 15Show fewer
  • 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

Trial locations and contacts

4 sites in 1 country.

Bangladesh4 sites

  • Bhaluka UZHC

    Bhaluka, Mymensingh

  • Gaffargaon

    Gafargaon, Mymensingh

  • Community Based Medical College

    Trishal, Mymensingh

  • Trishal UZHC

    Trishal, Mymensingh

Other trials in Bangladesh

About this study

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

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.

Read the 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.

Being tested
Liposomal amphotericin B, liposomal amphotericin B + miltefosine, liposomal amphotericin B + paromomycin, Miltefosine + Paromomycin
Keywords
visceral leishmaniasis, phase III, randomised ccontrolled trial, Bangladesh, Combination treatment, Ambisome, miltefosine, paromomycin
Medical subject headings
Leishmaniasis, Visceral

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Liposomal amphotericin BDrug

    Also called AmBisome

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

  • liposomal amphotericin B + miltefosineDrug

    Also called Impavido, AmBisome

    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)

  • liposomal amphotericin B + paromomycinDrug

    Also called Impavido

    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).

  • Miltefosine + ParomomycinDrug

    Also called Impavido

    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).

Study groups in NCT01122771
Study groupRoleWhat they receive
AmbisomeActive comparator15mg Ambisome on days 1,3 and 5
Receives: Drug: Liposomal amphotericin B
Ambisome + MiltefosineExperimentalAmbisome 5mg + miltefosine 10 days
Receives: Drug: liposomal amphotericin B + miltefosine
Ambisome +paromomycinExperimentalAmBisome IV infusion (single dose, day 1) + Paromomycin base 11mg/kg/day IM (Gland Pharma, India) for 10 days (days 2-11)
Receives: Drug: liposomal amphotericin B + paromomycin
Miltefosine + paromomycinExperimentalOral 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).
Receives: Drug: Miltefosine + Paromomycin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 6 month post treatment

Secondary outcomes (2)

  1. Initial Cure

    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

    Measured: Day 45

  2. Adverse events

    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

    Measured: Treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 May 2010 (estimated)
  2. Study startMay 2010
  3. Primary completionMar 2014
  4. Study completionMar 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
602 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01122771
Sponsor's protocol ID
VLCombo-BD-09
Status last verified
Jan 2016
First submitted
11 May 2010
Last updated
21 Jan 2016
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 28558062

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Liposomal amphotericin B, liposomal amphotericin B + miltefosine and liposomal amphotericin B + paromomycin in people with Visceral Leishmaniasis, run by Drugs for Neglected Diseases at 4 sites in Bangladesh.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Bangladesh. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Definitive cure (time frame: 6 month post treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01122771, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2016.

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