Clinical trial NCT00832208: Open-Label, Sequential Step, Safety and Efficacy Study to Determine the Optimal Single Dose of Ambisome for Patients With VL
Official title: Open-Label, Sequential Step, Safety and Efficacy Study to Determine the Optimal Single Dose of Ambisome for Patients With Visceral Leishmaniasis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Visceral Leishmaniasis
Lead sponsor: Drugs for Neglected Diseases
Sponsor class: OTHER
Collaborators: name: Addis Ababa University
First posted: 2009-01-30
Enrollment: 124
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase II/III open, comparative dose trial to find the lowest single dose of AmBisome for the treatment of primary, symptomatic visceral leishmaniasis(VL), in HIV negative patients. In this trial, the minimum effective dose will be determined in a sequential step, dose escalation design, which minimises the number of patients exposed to low, potentially inadequate doses and provides contemporaneous comparative data against the manufacturer's recommended dose schedule in this indication.


Eligibility criteria: Inclusion Criteria:

* Male and female adults and children aged 4 years or older with no upper age limit (in accordance with manufacturer's instructions)
* Acute, symptomatic, VL proven by parasitological examination of splenic aspirate (or bone marrow aspirate) with initial parasite index of at least 2+
* Haemoglobin \>4g/dL
* Fever for more than 2 weeks
* Living within reachable distance of the trial site to enable attendance for follow-up visits
* Written informed consent to participate (for children, by parent or guardian)
* HIV negative status

Exclusion Criteria:

* Patients 'in extremis' with signs/symptoms indicative of severe VL
* Patients who have received any anti-leishmanial treatment within the last 6 months
* Patients who have received any investigational (unlicensed) drugs during 6 months before recruitment
* Known underlying chronic disease, such as severe cardiac, pulmonary, renal, or hepatic impairment.
* Renal function tests (serum creatinine) outside the normal range
* Liver function tests more than 3 times the normal range at study entry
* Platelet count less than 40,000/ mm3
* Known alcohol abuse
* Pregnancy or lactation
* Concomitant acute drug usage for malaria and bacterial infection, pneumonia within last 7 days
* Known hypersensitivity to AmBisome or amphotericin B
* Any other condition which may invalidate the trial

Primary outcomes:
measure: The primary efficacy variable is parasitological clearance with no relapse at 6 months post treatment (ie definitive cure) assessed by clinical status and confirmed by splenic or bone marrow aspiration.
timeFrame: at 6 months post treatment
Secondary outcomes:
measure: Parasitological clearance at day 30.
timeFrame: Day 30
Other outcomes:
Locations:
city: Arba Minch
country: Ethiopia
facility: Arba Minch LRTC
city: Gondar
country: Ethiopia
facility: Gondar
city: Kassab
country: Sudan
facility: Kassab Hospital
state: Gedarif
Study officials:
affiliation: Gondar University
name: Sisay Yifru, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Khalil EA, Weldegebreal T, Younis BM, Omollo R, Musa AM, Hailu W, Abuzaid AA, Dorlo TP, Hurissa Z, Yifru S, Haleke W, Smith PG, Ellis S, Balasegaram M, EL-Hassan AM, Schoone GJ, Wasunna M, Kimutai R, Edwards T, Hailu A. Safety and efficacy of single dose versus multiple doses of AmBisome for treatment of visceral leishmaniasis in eastern Africa: a randomised trial. PLoS Negl Trop Dis. 2014 Jan 16;8(1):e2613. doi: 10.1371/journal.pntd.0002613. eCollection 2014.
citation: Edwards T, Omollo R, Khalil EA, Yifru S, Musa B, Musa A, Wasunna M, Smith PG, Royce C, Ellis S, Balasegaram M, Hailu A. Single-dose liposomal amphotericin B (AmBisome(R)) for the treatment of visceral leishmaniasis in East Africa: study protocol for a randomized controlled trial. Trials. 2011 Mar 6;12:66. doi: 10.1186/1745-6215-12-66.