Clinical trial NCT01067443: Clinical Trial to Assess the Safety and Efficacy of Sodium Stibogluconate (SSG) and AmBisome® Combination, Miltefosine and AmBisome® and Miltefosine Alone for the Treatment Visceral Leishmaniasis in Eastern Africa
Official title: A Phase II Randomized, Parallel Arm, Open-labeled Clinical Trial to Assess the Safety and Efficacy of the Combination of Sodium Stibogluconate Plus Single Dose AmBisome®, Miltefosine Plus Single Dose AmBisome® and Miltefosine Alone for the Treatment of Primary Visceral Leishmaniasis in Eastern Africa
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Visceral Leishmaniasis
Keywords: Phase II
Randomised clinical trial
Visceral Leishmaniasis
Lead sponsor: Drugs for Neglected Diseases
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
name: Paladin Labs Inc.
First posted: 2010-02-11
Enrollment: 151
Sex: ALL
Minimum age (years): 7
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is to assess if shorter combinations of SSG plus single dose AmBisome®, Miltefosine plus single dose AmBisome® and Miltefosine alone are effective in treating visceral leishmaniasis in Eastern Africa.

Detailed description: The current study intends to look at potential feasible short course combination therapies as well as evaluate (and possibly register) miltefosine in its conventional dose against VL in Sudan and Kenya.

Eligibility criteria: Inclusion Criteria:

* Patients with clinical signs and symptoms of VL and diagnosis confirmed by visualization of parasites in tissue samples (lymph node, bone marrow or spleen where relevant) on microscopy.
* Patients aged between 7 (to allow for blood sampling) and 60 years (inclusive) who are able to comply with the protocol.
* Patients for whom written informed consent has been signed by the patients themselves (if aged 18 years and over) or by parents(s) or legal guardian for patients under 18 years of age.
* HIV negative status

Exclusion Criteria:

* Patients who have received any anti-leishmanial drugs in the last 6 months/ relapse cases.
* Patients with a negative lymph node/bone marrow (or spleen) smears.
* Patients with severe protein and or caloric malnutrition (Kwashiorkor or marasmus ; Adults: BMI \</= 15, Children W/H\<70, presence of oedema)
* Patients with previous history of hypersensitivity reaction to SSG or Amphotericin B.
* Patients suffering from a concomitant severe infection such as TB or any other serious underlying disease (cardiac, renal, hepatic) which would preclude evaluation of the patient's response to study medication.
* Patients suffering from other conditions associated with splenomegaly such as schistosomiasis.
* Patients with previous history of cardiac arrhythmia or an abnormal ECG
* Patients who are female of child bearing age (all females who have achieved menarche) / pregnant or lactating.
* Patients with haemoglobin \< 5gm/dl.
* Patients with WBC \< 1 x 10³/mm³.
* Patients with platelets \< 40,000/mm³.
* Patients with abnormal liver function (ALT and AST) tests of more than three times the normal range.
* Patients with serum creatinine outside the normal range for age and gender.
* Major surgical intervention within 2 weeks prior to enrolment.

Primary outcomes:
measure: Initial cure: proportion cured at Day 28
timeFrame: Day 28
Secondary outcomes:
measure: Final cure: proportion cured at day 210
timeFrame: 6 months post treatment
measure: Adverse events and serious adverse events occurring in the three study arms
timeFrame: up to day 60
Other outcomes:
Locations:
city: Kimalel
country: Kenya
facility: Kimalel Health Centre
city: Kassab
country: Sudan
facility: Kassab Hospital
state: Gedaref
city: Doka
country: Sudan
facility: El Hassan Centre for Tropical Medicine
state: Gedarif
Study officials:
affiliation: Kenya Medical Research Institute
name: Monique Wasunna, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wasunna M, Njenga S, Balasegaram M, Alexander N, Omollo R, Edwards T, Dorlo TP, Musa B, Ali MH, Elamin MY, Kirigi G, Juma R, Kip AE, Schoone GJ, Hailu A, Olobo J, Ellis S, Kimutai R, Wells S, Khalil EA, Strub Wourgaft N, Alves F, Musa A. Efficacy and Safety of AmBisome in Combination with Sodium Stibogluconate or Miltefosine and Miltefosine Monotherapy for African Visceral Leishmaniasis: Phase II Randomized Trial. PLoS Negl Trop Dis. 2016 Sep 14;10(9):e0004880. doi: 10.1371/journal.pntd.0004880. eCollection 2016 Sep.
citation: Allison A, Edwards T, Omollo R, Alves F, Magirr D, E Alexander ND. Generalizing boundaries for triangular designs, and efficacy estimation at extended follow-ups. Trials. 2015 Nov 16;16:522. doi: 10.1186/s13063-015-1018-1.
citation: Omollo R, Alexander N, Edwards T, Khalil EA, Younis BM, Abuzaid AA, Wasunna M, Njoroge N, Kinoti D, Kirigi G, Dorlo TP, Ellis S, Balasegaram M, Musa AM. Safety and efficacy of miltefosine alone and in combination with sodium stibogluconate and liposomal amphotericin B for the treatment of primary visceral leishmaniasis in East Africa: study protocol for a randomized controlled trial. Trials. 2011 Jun 30;12:166. doi: 10.1186/1745-6215-12-166.