Efficacy and Safety Study of Drugs for Treatment of Visceral Leishmaniasis in Brazil (LVBrasil)
|Visceral Leishmaniasis||Drug: Antimoniate of N-methylglucamine Drug: amphotericin B deoxycholate Drug: Liposomal amphotericin B||Phase 4|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Multicentric Efficacy and Safety Study of Antileishmanial Drugs for Treatment of Visceral Leishmaniasis in Brazil|
- Cure rate [ Time Frame: 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.
- Improvement rate [ Time Frame: 30 days ]Fever disappearing, stable or improving hematological lab abnormalities plus any spleen size reduction.
- Relapse rate [ Time Frame: (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.
- Serious adverse events rate [ Time Frame: 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 [ Time Frame: 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.
|Study Start Date:||February 2011|
|Study Completion Date:||February 2015|
|Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
Active Comparator: Meglumine antimoniate
Antimoniate of N-methylglucamine 20mg/kg/d, I.V. for 20 consecutive days.
Drug: Antimoniate of N-methylglucamine
Antimoniate of N-methyl glucamine 20mg/kg/d of pentavalent antimonial, I.V. for 20 consecutive days.
Other Name: Glucantime
Experimental: Liposomal Amphotericin B
Liposomal amphotericin B 3mg/kg/d I.V. for 7 consecutive days.
Drug: Liposomal amphotericin B
3mg/kg/d, I.V. for 7 consecutive days.
Other Name: AmBisome
Experimental: Amphotericin B
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
1mg/kg/d, I.V. for 14 consecutive days.
Experimental: Combination therapy
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
10mg/kg/d, I.V. single dose.
Other Name: AmBisomeDrug: Antimoniate of N-methylglucamine
20mg/kg/d of pentavalent antimonial I.V. for 10 days
Other Name: Glucantime
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01310738
|Hospital Universitário da Universidade Federal de Sergipe|
|Sergipe, Aracaju, Brazil, 49060-100|
|Hospital São José de Doenças Infecciosas|
|Fortaleza, Ceará, Brazil, 60455610|
|Hospital Infantil João Paulo II - FHEMIG|
|Belo Horizonte, Minas Gerais, Brazil, 30130-110|
|Hospital Universitário Clemente de Faria - Universidade Estadual de Montes Claros|
|Montes Claros, Minas Gerais, Brazil, 39401-002|
|Hospital de Doencas Infecto Contagiosas - HDIC|
|Teresina, Piaui, Brazil, 64001450|
|Principal Investigator:||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|
|Study Director:||Fabiana P Alves, MD PhD||Drugs for Neglected Diseases|
|Study Chair:||Gustavo AS Romero, MD PhD||University of Brasilia|
|Principal Investigator:||Robério D Leite, MD, PhD||Hospital São José de Doenças Infecciosas, Secretaria de Saúde do Estado do Ceará.|