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| ID | Type | Description | Link |
|---|---|---|---|
| 559819/2010-2 | Other Grant/Funding Number | CNPq - Brazil | |
| 108042500 | Other Grant/Funding Number | Finaciadora de Estudos e Projetos - FINEP - Brazil | |
| CAAE 0973.1.000.245-10 | Other Identifier | Brazilian National Ethics Council |
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DSMB recommendation based on programmed interim analysis.
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| Name | Class |
|---|---|
| Ministry of Health, Brazil | OTHER_GOV |
| Drugs for Neglected Diseases | OTHER |
| Conselho Nacional de Desenvolvimento Científico e Tecnológico | OTHER_GOV |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Meglumine antimoniate | Active Comparator | Antimoniate of N-methylglucamine 20mg/kg/d, I.V. for 20 consecutive days. |
|
| Liposomal Amphotericin B | Experimental | Liposomal amphotericin B 3mg/kg/d I.V. for 7 consecutive days. |
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| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Antimoniate of N-methylglucamine | Drug | Antimoniate of N-methyl glucamine 20mg/kg/d of pentavalent antimonial, I.V. for 20 consecutive days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Improvement rate | Fever disappearing, stable or improving hematological lab abnormalities plus any spleen size reduction. | 30 days |
| Relapse rate | Reappearing of signs and symptoms after any improvement observed after treatment, during the six months follow-up period. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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. |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Universitário da Universidade Federal de Sergipe | Sergipe | Aracaju | 49060-100 | Brazil | ||
| Hospital São José de Doenças Infecciosas |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28662034 | Result | 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. |
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| amphotericin B deoxycholate | Drug | 1mg/kg/d, I.V. for 14 consecutive days. |
|
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| Liposomal amphotericin B | Drug | 3mg/kg/d, I.V. for 7 consecutive days. |
|
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| Liposomal amphotericin B | Drug | 10mg/kg/d, I.V. single dose. |
|
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| Antimoniate of N-methylglucamine | Drug | 20mg/kg/d of pentavalent antimonial I.V. for 10 days |
|
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| (6 months post treatment) After treatment until the sixth month of follow-up |
| 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 |
| 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 |
| Fortaleza |
| Ceará |
| 60455610 |
| Brazil |
| Hospital Infantil João Paulo II - FHEMIG | Belo Horizonte | Minas Gerais | 30130-110 | Brazil |
| Hospital Universitário Clemente de Faria - Universidade Estadual de Montes Claros | Montes Claros | Minas Gerais | 39401-002 | Brazil |
| Hospital de Doencas Infecto Contagiosas - HDIC | Teresina | Piauí | 64001450 | Brazil |
| ID | Term |
|---|---|
| D007898 | Leishmaniasis, Visceral |
| ID | Term |
|---|---|
| D007896 | Leishmaniasis |
| D056986 | Euglenozoa Infections |
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
| D000079426 | Vector Borne Diseases |
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| ID | Term |
|---|---|
| D000077485 | Meglumine Antimoniate |
| C059765 | amphotericin B, deoxycholate drug combination |
| D000666 | Amphotericin B |
| C068538 | liposomal amphotericin B |
| ID | Term |
|---|---|
| D008536 | Meglumine |
| D013012 | Sorbitol |
| D013402 | Sugar Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D006595 | Hexosamines |
| D000606 | Amino Sugars |
| D002241 | Carbohydrates |
| D018942 | Macrolides |
| D061065 | Polyketides |
| D007783 | Lactones |
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