Clinical trial NCT01310738: Efficacy and Safety Study of Drugs for Treatment of Visceral Leishmaniasis in Brazil
Official title: Multicentric Efficacy and Safety Study of Antileishmanial Drugs for Treatment of Visceral Leishmaniasis in Brazil
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Visceral Leishmaniasis
Keywords: Visceral leishmaniasis
Leishmania infantum
Leishmania chagasi
Lead sponsor: University of Brasilia
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Brazil
name: Drugs for Neglected Diseases
name: Conselho Nacional de Desenvolvimento Científico e Tecnológico
First posted: 2011-03-08
Enrollment: 378
Sex: ALL
Minimum age (years): 6
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Cure rate
timeFrame: 6 month
Secondary outcomes:
measure: Improvement rate
timeFrame: 30 days
measure: Relapse rate
timeFrame: (6 months post treatment) After treatment until the sixth month of follow-up
measure: Serious adverse events rate
timeFrame: During (day one) and within the six months follow-up
measure: Adverse event rate and intensity
timeFrame: During (day one) treatment and within the six months follow-up
Other outcomes:
Locations:
city: Sergipe
country: Brazil
facility: Hospital Universitário da Universidade Federal de Sergipe
state: Aracaju
city: Fortaleza
country: Brazil
facility: Hospital São José de Doenças Infecciosas
state: Ceará
city: Belo Horizonte
country: Brazil
facility: Hospital Infantil João Paulo II - FHEMIG
state: Minas Gerais
city: Montes Claros
country: Brazil
facility: Hospital Universitário Clemente de Faria - Universidade Estadual de Montes Claros
state: Minas Gerais
city: Teresina
country: Brazil
facility: Hospital de Doencas Infecto Contagiosas - HDIC
state: Piaui
Study officials:
affiliation: Federal University of Piaui
name: Carlos HN Costa, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Federal University of Piaui
name: Dorcas L Costa, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro de Pesquisas Rene Rachou - Fiocruz - Minas Gerais
name: Ana LT Rabello, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Montes Claros State University - Unimontes
name: Silvio FG de Carvalho, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Infantil Joao Paulo II - FHEMIG
name: Andrea L de Carvalho, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Federal University of Sergipe
name: Roque P de Almeida, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Drugs for Neglected Diseases
name: Fabiana P Alves, MD PhD
role: STUDY_DIRECTOR
affiliation: University of Brasilia
name: Gustavo AS Romero, MD PhD
role: STUDY_CHAIR
affiliation: Hospital São José de Doenças Infecciosas, Secretaria de Saúde do Estado do Ceará.
name: Robério D Leite, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 leishmaniasis in Brazil: A multicenter, randomized, open label trial. PLoS Negl Trop Dis. 2017 Jun 29;11(6):e0005706. doi: 10.1371/journal.pntd.0005706. eCollection 2017 Jun.