Efficacy and Safety Study of Drugs for Treatment of Visceral Leishmaniasis in Brazil
Multicentric Efficacy and Safety Study of Antileishmanial Drugs for Treatment of Visceral Leishmaniasis in Brazil
Lead SponsorUniversity of Brasilia
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.
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.
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.
3mg/kg/d, I.V. for 7 consecutive days.
10mg/kg/d, I.V. single dose.
20mg/kg/d of pentavalent antimonial I.V. for 10 days
Antimoniate of N-methylglucamine 20mg/kg/d, I.V. for 20 consecutive days.
Liposomal amphotericin B 3mg/kg/d I.V. for 7 consecutive days.
Amphotericin B deoxycholate 1mg/kg/d I.V. for 14 consecutive days. This arm was suspended in September 19th, 2012, because of a relevant excess of adverse events and serious adverse events associated with this experimental intervention in comparison with the active comparator and the other two experimental arms. The suspension of this study arm was supported by a DSMB statement.
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