NCT02011958

Brief Summary

The overall objective of this trial is to identify a safe and effective treatment for visceral leishmaniasis (VL) in HIV co-infected Ethiopian patients. Patients will receive either Ambisome alone or Ambisome in combination with Miltefosine. Patients who do not undergo treatment failure will be given a VL prophylactic treatment with Pentamidine one month after the end of the study treatment.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
59

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Jul 2014

Typical duration for phase_3

Geographic Reach
1 country

2 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

First Submitted

Initial submission to the registry

November 18, 2013

Completed
28 days until next milestone

First Posted

Study publicly available on registry

December 16, 2013

Completed
7 months until next milestone

Study Start

First participant enrolled

July 1, 2014

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2016

Completed
1.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 15, 2017

Completed
Last Updated

April 8, 2019

Status Verified

April 1, 2019

Enrollment Period

2.1 years

First QC Date

November 18, 2013

Last Update Submit

April 4, 2019

Conditions

Visceral Leishmaniasis

Keywords

Visceral LeishmaniasisHIV positive patientsPhase III trialRandomisedLiposomal amphotericin BAmbisomeMiltefosinePentamidineEfficacySafety

Outcome Measures

Primary Outcomes (1)

  • Initial parasitological cure at day 29

    Absence of parasites in tissue aspirate at day 29; hence no rescue medication provided up to this time-point.

    Day 29

Secondary Outcomes (1)

  • Relapse-free survival at day 390

    Day 390

Other Outcomes (3)

  • Safety endpoint

    From the first dose of study medication up to 1 month after the stop of treatment

  • Response to antiretroviral treatment

    Screening , Day 29, Day 58, Day 210 and Day 390

  • Pharmacokinetics: drug-drug interaction between VL treatment and antiretroviral drugs (Arm 1: PK AmphoB (Amphotericin B) and PK/EFV (Efavirenz)/NVP (Nevirapine)/LPV (Lopinavir)/RTV, Arm 2: PK AmphoB, PK Miltefosine and PK EFV/NVP/LPV/RTV)

    Arm1:PK AmphoB, Day 1 and 24 post-dose / PK EFV/NVP/LPV/RTV: Day 1,24,58,210 and 390 post-dose. Arm 2: PK AmphoB, Day 1 and 11 post-dose/PK Miltefosine: Pre-dose, day 11,29,58,210 post-dose / PK EFV/NVP/LPV/RTV: Day 1,29,58,210 and 390 post-dose

Study Arms (2)

Liposomal Amphotericin B / Miltefosine

EXPERIMENTAL

Liposomal Amphotericin B : 30mg/kg total dose: IV infusion 5mg/kg per day on day 1, 3, 5, 7, 9, 11 Miltefosine: orally taken every day during 28 days * 1 x 50 mg capsule per day if patient weights less or equal to 25 kg * 2 x 50 mg capsules per day if the patient weights more than 25 kg

Drug: Liposomal Amphotericin BDrug: Miltefosine

Liposomal Amphotericin B

EXPERIMENTAL

Liposomal Amphotericin B: 40 mg/kg total dose : IV infusion of 5mg/kg per day on day 1 to 5, 10, 17, 24

Drug: Liposomal Amphotericin B

Interventions

Liposomal Amphotericin BDRUG

40 mg/kg total dose: IV infusion of 5mg/kg per day on day 1 to 5, 10,17,24 (when administered as a monotherapy) 30 mg/kg total dose: IV infusion 5 mg/kg per day on day 1, 3, 5, 7, 9, 11 (when administered in combination with Miltefosine)

Also known as: Ambisome
Liposomal Amphotericin BLiposomal Amphotericin B / Miltefosine
MiltefosineDRUG

Orally taken every day during 28 days * 1 x 50 mg capsule per day if the patient weights less or equal to 25 kg * 2 x 50 mg capsules per day if the patient weights more than 25 kg (1 capsule in the morning / 1 capsule in the evening)

Also known as: Impavido
Liposomal Amphotericin B / Miltefosine

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Confirmed HIV positive test (2 rapid diagnostics tests (RDTs) followed by a confirmatory ELISA test).
  • Diagnosis of VL (first episode or relapse) confirmed by bone marrow or spleen aspirate.
  • Male and female age: 18-60 years.
  • Written informed consent from the patient.

You may not qualify if:

  • 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 four months after.
  • Pregnant women or breast-feeding mothers.
  • Patients with grade 2 or 3 post kala-azar dermal leishmaniasis (PKDL) lesions.
  • Clinical or biological evidence of severe cardiac, renal or hepatic impairment.
  • Known hypersensitivity to AmBisome® and/or miltefosine.
  • Patients receiving allopurinol treatment

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

MSF

Abdurafi, Ethiopia

Location

Leishmaniasis Research Center, University Hospital of Gondar

Gonder, Ethiopia

Location

Related Publications (2)

  • Diro E, Blesson S, Edwards T, Ritmeijer K, Fikre H, Admassu H, Kibret A, Ellis SJ, Bardonneau C, Zijlstra EE, Soipei P, Mutinda B, Omollo R, Kimutai R, Omwalo G, Wasunna M, Tadesse F, Alves F, Strub-Wourgaft N, Hailu A, Alexander N, Alvar J. A randomized trial of AmBisome monotherapy and AmBisome and miltefosine combination to treat visceral leishmaniasis in HIV co-infected patients in Ethiopia. PLoS Negl Trop Dis. 2019 Jan 17;13(1):e0006988. doi: 10.1371/journal.pntd.0006988. eCollection 2019 Jan.

    PMID: 30653490RESULT

  • Diro E, Edwards T, Ritmeijer K, Fikre H, Abongomera C, Kibret A, Bardonneau C, Soipei P, Mutinda B, Omollo R, van Griensven J, Zijlstra EE, Wasunna M, Alves F, Alvar J, Hailu A, Alexander N, Blesson S. Long term outcomes and prognostics of visceral leishmaniasis in HIV infected patients with use of pentamidine as secondary prophylaxis based on CD4 level: a prospective cohort study in Ethiopia. PLoS Negl Trop Dis. 2019 Feb 21;13(2):e0007132. doi: 10.1371/journal.pntd.0007132. eCollection 2019 Feb.

    PMID: 30789910RESULT

MeSH Terms

Conditions

Leishmaniasis, Visceral

Interventions

liposomal amphotericin Bmiltefosine

Condition Hierarchy (Ancestors)

LeishmaniasisEuglenozoa InfectionsProtozoan InfectionsParasitic DiseasesInfectionsVector Borne Diseases

Study Officials

  • Ermias Diro, Dr. MD

    University of Gondar

    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

November 18, 2013

First Posted

December 16, 2013

Study Start

July 1, 2014

Primary Completion

August 1, 2016

Study Completion

September 15, 2017

Last Updated

April 8, 2019

Record last verified: 2019-04

Locations

ET(2)