Efficacy and Safety Study of Drugs for Treatment of Visceral Leishmaniasis in Brazil

Visceral Leishmaniasis Clinical Trial

— LVBrasil  

Official title:

Multicentric Efficacy and Safety Study of Antileishmanial Drugs for Treatment of Visceral Leishmaniasis in Brazil

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01310738
• Other study ID #: LVBrasil_2007
• Secondary ID: 559819/2010-2108
• Status: Terminated
• Phase: Phase 4
• First received: March 7, 2011
• Last updated: August 31, 2017
• Start date: February 2011
• Est. completion date: February 2015

Study information

• Verified date: August 2017
• Source: University of Brasilia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 378
• Est. completion date: February 2015
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Leishmaniasis
• Leishmaniasis, Visceral
• Visceral Leishmaniasis

Intervention

Drug:
• Antimoniate of N-methylglucamine
Antimoniate of N-methyl glucamine 20mg/kg/d of pentavalent antimonial, I.V. for 20 consecutive days.
• amphotericin B deoxycholate
1mg/kg/d, I.V. for 14 consecutive days.
• Liposomal amphotericin B
3mg/kg/d, I.V. for 7 consecutive days.
• Liposomal amphotericin B
10mg/kg/d, I.V. single dose.
• Antimoniate of N-methylglucamine
20mg/kg/d of pentavalent antimonial I.V. for 10 days

Locations

Country	Name	City	State
Brazil	Hospital Infantil João Paulo II - FHEMIG	Belo Horizonte	Minas Gerais
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 Universitário da Universidade Federal de Sergipe	Sergipe	Aracaju
Brazil	Hospital de Doencas Infecto Contagiosas - HDIC	Teresina	Piaui

Sponsors (4)

Lead Sponsor	Collaborator
University of Brasilia	Conselho Nacional de Desenvolvimento Científico e Tecnológico, Drugs for Neglected Diseases, Ministry of Health, Brazil

Country where clinical trial is conducted

Brazil, 

References & Publications (1)

Romero GAS, Costa DL, Costa CHN, de Almeida RP, de Melo EV, de Carvalho SFG, Rabello A, de Carvalho AL, Sousa AQ, Leite RD, Lima SS, Amaral TA, Alves FP, Rode J; Collaborative LVBrasil Group. Efficacy and safety of available treatments for visceral leishm — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cure rate	Complete remission of clinical signs and symptoms, three months after treatment plus normal hematological lab evaluation and no relapse at sixth month follow-up.	6 month
Secondary	Improvement rate	Fever disappearing, stable or improving hematological lab abnormalities plus any spleen size reduction.	30 days
Secondary	Relapse rate	Reappearing of signs and symptoms after any improvement observed after treatment, during the six months follow-up period.	(6 months post treatment) After treatment until the sixth month of follow-up
Secondary	Serious adverse events rate	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.	During (day one) and within the six months follow-up
Secondary	Adverse event rate and intensity	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.	During (day one) treatment and within the six months follow-up