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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Primary Visceral Leishmaniasis

Intervention / Treatment
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* Drug: Liposomal amphotericin B (AmBisome®) and sodium stibogluconate
* Drug: Liposomal amphotericin B + miltefosine
* Drug: Miltefosine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amb+SSG<br>AmBisome® one dose of 10mg/kg body weight (IV) on day 1 followed by 10 days of SSG at 20mg/kg body weight (IV/IM) from days 2-11 | Drug: Liposomal amphotericin B (AmBisome®) and sodium stibogluconate<br>* AmBisome® one dose of 10mg/kg body weight (IV) on day 1 followed by 10 days of SSG at 20mg/kg body weight (IV/IM) from days 2-11<br>|
| Experimental: Amb+Milt<br>AmBisome® one dose of 10mg/kg body weight (IV) on day 1 followed by 10 days Miltefosine at 2.5mg/kg body weight (oral) from days 2-11 | Drug: Liposomal amphotericin B + miltefosine<br>* AmBisome® one dose of 10mg/kg body weight (IV) on day 1 followed by 10 days Miltefosine at 2.5mg/kg body weight (oral) from days 2-11<br>|
| Experimental: Milt<br>Monotherapy course of Miltefosine at 2.5mg/kg body weight (oral) from days 1-28 | Drug: Miltefosine<br>* Monotherapy course of Miltefosine at 2.5mg/kg body weight (oral) from days 1-28<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Initial cure: proportion cured at Day 28 |  | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Final cure: proportion cured at day 210 |  | 6 months post treatment | 
| Adverse events and serious adverse events occurring in the three study arms |  | up to day 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase II, Randomised clinical trial, Visceral Leishmaniasis