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

Drugs for Neglected Diseases

Status and phase: Completed; Phase 2

Conditions: Primary Visceral Leishmaniasis

Treatments: Drug: Miltefosine; Drug: Liposomal amphotericin B (AmBisome®) and sodium stibogluconate; Drug: Liposomal amphotericin B + miltefosine

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01067443

LEAP 0208

Details and patient eligibility

About

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.

Full 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.

Enrollment: 151 patients

Sex: All

Ages: 7 to 60 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

151 participants in 3 patient groups

Amb+SSG

Experimental group

Description:

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

Treatment:

Drug: Liposomal amphotericin B (AmBisome®) and sodium stibogluconate

Amb+Milt

Experimental group

Description:

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

Treatment:

Drug: Liposomal amphotericin B + miltefosine

Milt

Experimental group

Description:

Monotherapy course of Miltefosine at 2.5mg/kg body weight (oral) from days 1-28

Treatment:

Drug: Miltefosine