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

NCT01310738 | Terminated Phase 4 DMC

• 4 other identifiers: LVBrasil_2007559819/2010-2108042500CAAE 0973.1.000.245-10
• Study Type: interventional
• Target: 378
• Locations: 1 country
• Sites: 5

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.

Conditions

Visceral Leishmaniasis

Keywords

Visceral leishmaniasis; Leishmania infantum; Leishmania chagasi

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Improvement rate

  30 days

• Relapse rate

  (6 months post treatment) After treatment until the sixth month of follow-up

• Serious adverse events rate

  During (day one) and within the six months follow-up

• Adverse event rate and intensity

  During (day one) treatment and within the six months follow-up

Study Arms (4)

Meglumine antimoniate

ACTIVE COMPARATOR

Antimoniate of N-methylglucamine 20mg/kg/d, I.V. for 20 consecutive days.

Drug: Antimoniate of N-methylglucamine

Liposomal Amphotericin B

EXPERIMENTAL

Liposomal amphotericin B 3mg/kg/d I.V. for 7 consecutive days.

Drug: Liposomal amphotericin B

Amphotericin B

EXPERIMENTAL

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.

Drug: amphotericin B deoxycholate

Combination therapy

EXPERIMENTAL

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.

Drug: Liposomal amphotericin B; Drug: Antimoniate of N-methylglucamine

Interventions

Antimoniate of N-methylglucamine DRUG

Antimoniate of N-methyl glucamine 20mg/kg/d of pentavalent antimonial, I.V. for 20 consecutive days.

Also known as: Glucantime

Meglumine antimoniate

amphotericin B deoxycholate DRUG

1mg/kg/d, I.V. for 14 consecutive days.

Also known as: Fungizone, Anforicin B

Amphotericin B

Liposomal amphotericin B DRUG

3mg/kg/d, I.V. for 7 consecutive days.

Also known as: AmBisome

Liposomal Amphotericin B

Eligibility Criteria

• Age: 6 Months - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Brasilia: lead
• Ministry of Health, Brazil: collaborator
• Drugs for Neglected Diseases: collaborator
• Conselho Nacional de Desenvolvimento Científico e Tecnológico: collaborator

Study Sites (5)

Hospital Universitário da Universidade Federal de Sergipe

Sergipe, Aracaju, 49060-100, Brazil

Location

Hospital São José de Doenças Infecciosas

Fortaleza, Ceará, 60455610, Brazil

Location

Hospital Infantil João Paulo II - FHEMIG

Belo Horizonte, Minas Gerais, 30130-110, Brazil

Location

Hospital Universitário Clemente de Faria - Universidade Estadual de Montes Claros

Montes Claros, Minas Gerais, 39401-002, Brazil

Location

Hospital de Doencas Infecto Contagiosas - HDIC

Teresina, Piauí, 64001450, Brazil

Location

Related 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 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.

  PMID: 28662034 RESULT

MeSH Terms

Conditions

Leishmaniasis, Visceral

Interventions

Meglumine Antimoniate; amphotericin B, deoxycholate drug combination; Amphotericin B; liposomal amphotericin B

Condition Hierarchy (Ancestors)

Leishmaniasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Meglumine; Sorbitol; Sugar Alcohols; Alcohols; Organic Chemicals; Hexosamines; Amino Sugars; Carbohydrates; Macrolides; Polyketides; Lactones

Study Officials

• Carlos HN Costa, MD PhD

  Federal University of Piaui

  PRINCIPAL INVESTIGATOR

• Dorcas L Costa, MD PhD

  Federal University of Piaui

  PRINCIPAL INVESTIGATOR

• Ana LT Rabello, MD PhD

  Centro de Pesquisas Rene Rachou - Fiocruz - Minas Gerais

  PRINCIPAL INVESTIGATOR

• Silvio FG de Carvalho, MD PhD

  Montes Claros State University - Unimontes

  PRINCIPAL INVESTIGATOR

• Andrea L de Carvalho, MD

  Hospital Infantil Joao Paulo II - FHEMIG

  PRINCIPAL INVESTIGATOR

• Roque P de Almeida, MD PhD

  Federal University of Sergipe

  PRINCIPAL INVESTIGATOR

• Fabiana P Alves, MD PhD

  Drugs for Neglected Diseases

  STUDY DIRECTOR

• Gustavo AS Romero, MD PhD

  University of Brasilia

  STUDY CHAIR

• Robério D Leite, MD, PhD

  Hospital São José de Doenças Infecciosas, Secretaria de Saúde do Estado do Ceará.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 7, 2011
• First Posted: March 8, 2011
• Study Start: February 1, 2011
• Primary Completion: October 1, 2014
• Study Completion: February 1, 2015
• Last Updated: September 5, 2017

Record last verified: 2017-08

Locations

BR (5)