Efficacy and Safety Study of Drugs for Treatment of Visceral Leishmaniasis in Brazil
- Conditions
- Visceral Leishmaniasis
- Interventions
- Drug: Antimoniate of N-methylglucamine
- Registration Number
- NCT01310738
- Lead Sponsor
- University of Brasilia
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 378
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Combination therapy Liposomal amphotericin B Liposomal amphotericin B 10mg/kg/d, I.V. single dose on day 0 plus Antimoniate of N-methylglucamine 20mg/kg/d for 10 consecutive days on days 1 to 10. Liposomal Amphotericin B Liposomal amphotericin B Liposomal amphotericin B 3mg/kg/d I.V. for 7 consecutive days. Combination therapy Antimoniate of N-methylglucamine Liposomal amphotericin B 10mg/kg/d, I.V. single dose on day 0 plus Antimoniate of N-methylglucamine 20mg/kg/d for 10 consecutive days on days 1 to 10. Meglumine antimoniate Antimoniate of N-methylglucamine Antimoniate of N-methylglucamine 20mg/kg/d, I.V. for 20 consecutive days. Amphotericin B amphotericin B deoxycholate 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.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
Improvement rate 30 days Fever disappearing, stable or improving hematological lab abnormalities plus any spleen size reduction.
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.
Trial Locations
- Locations (5)
Hospital Universitário da Universidade Federal de Sergipe
🇧🇷Sergipe, Aracaju, Brazil
Hospital de Doencas Infecto Contagiosas - HDIC
🇧🇷Teresina, Piaui, Brazil
Hospital São José de Doenças Infecciosas
🇧🇷Fortaleza, Ceará, Brazil
Hospital Universitário Clemente de Faria - Universidade Estadual de Montes Claros
🇧🇷Montes Claros, Minas Gerais, Brazil
Hospital Infantil João Paulo II - FHEMIG
🇧🇷Belo Horizonte, Minas Gerais, Brazil