Visceral Leishmaniasis
Conditions
Keywords
Visceral leishmaniasis, Leishmania infantum, Leishmania chagasi
Brief summary
This study is aimed to compare the efficacy and safety of medications currently used in Brazil for treatment of visceral leishmaniasis. The investigators will compare the effects of meglumine antimoniate, two formulations of amphotericin B: deoxycholate and liposomal, and a combination of meglumine plus the liposomal amphotericin B formulation. The study is designed to demonstrate the difference in efficacy measured as cure rate at six months after treatment and the safety profile based on the adverse event rate observed with each intervention.
Detailed description
Visceral leishmaniasis is a relevant public health problem in Brazil with approximately 3500 cases registered every year. Eight percent lethality rate has been observed during the past decade in spite of free of charge availability of antileishmanial drugs supplied by the public health system. The present study was designed as a phase IV, multicentric, open label, active controlled clinical trial targeted to visceral leishmaniasis adult and pediatric cases. The current drugs approved for visceral leishmaniasis treatment in Brazil will be compared in four treatment groups: meglumine antimoniate, amphotericin B deoxycholate, liposomal amphotericin B and a combination of single dose of liposomal amphotericin B plus meglumine antimoniate. Meglumine antimoniate treated patients will constitute the active control group. Drugs will be compared based on the cure rate observed after six months follow-up. The study arm submitted to treatment with Amphotericin B deoxycholate was suspended in September 2012.
Interventions
DRUGAntimoniate of N-methylglucamine
Antimoniate of N-methyl glucamine 20mg/kg/d of pentavalent antimonial, I.V. for 20 consecutive days.
1mg/kg/d, I.V. for 14 consecutive days.
DRUGLiposomal amphotericin B
3mg/kg/d, I.V. for 7 consecutive days.
Sponsors
Ministry of Health, Brazil
Drugs for Neglected Diseases
Conselho Nacional de Desenvolvimento Científico e Tecnológico
University of Brasilia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 50 Years
Healthy volunteers
No
Inclusion criteria
* patients with visceral leishmaniasis characterized by fever plus hepatomegaly or splenomegaly with at least one positive result in the following laboratory tests: * direct observation of leishmania amastigotes in bone marrow smear * leishmania in vitro culture from bone marrow aspirates * leishmania kDNA amplification by PCR in bone marrow or peripheral blood samples * rK39 immunochromatographic rapid test performed on serum sample
Exclusion criteria
* pregnancy * HIV infection * chronic diseases such as diabetes mellitus,kidney, liver or cardiac diseases, schistosomiasis, malaria or tuberculosis * immune disorders or use of drugs which interferes with the immune response * treatment with drugs with increased risk for toxicity associated with the study drugs * exposure to antileishmanial drugs during the past six months * I.V. drug users * episodes of visceral leishmaniasis relapse * hypersensibility to the study drugs * difficulties for accomplishing the follow-up schedule * any of the following clinical signs of laboratory abnormalities: hepatic encephalopathy, generalized edema, toxemic individuals, severe malnutrition, jaundice, abnormal serum creatinine, bilirubin, INR \> 2,0, platelet count \< 20000/mm3
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cure rate | 6 month | Complete remission of clinical signs and symptoms, three months after treatment plus normal hematological lab evaluation and no relapse at sixth month follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvement rate | 30 days | Fever disappearing, stable or improving hematological lab abnormalities plus any spleen size reduction. |
| Relapse rate | (6 months post treatment) After treatment until the sixth month of follow-up | Reappearing of signs and symptoms after any improvement observed after treatment, during the six months follow-up period. |
| Serious adverse events rate | During (day one) and within the six months follow-up | Rate of adverse events defined as conditions which fulfilled any of the following: results in death, is life threatening, requires inpatient hospitalization or prolongs hospitalization, results in persistent or significant disability/incapacity, causes a congenital anomaly or birth defect or it is considered as a important medical event for the responsible clinician. |
| Adverse event rate and intensity | During (day one) treatment and within the six months follow-up | Cumulative rate of any adverse event, including clinical, laboratory and electrocardiographic abnormalities observed within the treatment and follow-up periods. All adverse events will be graded using an adapted ACTG 0-4 scale. |
Countries
Brazil
Outcome results
None listed