Clinical trial NCT01032187: Amphotericin B to Treat Visceral Leishmaniasis in Brazilian Children
Official title: Efficacy and Safety of Amphotericin B Deoxycholate Compared to Meglumine Antimoniate for Treatment of Visceral Leishmaniasis in Brazilian Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Visceral Leishmaniasis
Keywords: Visceral leishmaniasis
Amphotericin B deoxycholate
Meglumine antimoniate
Children
Brazil
Lead sponsor: University of Brasilia
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Brazil
First posted: 2009-12-15
Enrollment: 101
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if amphotericin B is effective against visceral leishmaniasis in Brazilian children. Amphotericin B will be compared to meglumine antimoniate which is the current approved drug used for this disease in Brazil.

Detailed description: Despite their high toxicity, antimonials and amphotericin B deoxycholate are commonly used for treating visceral leishmaniasis (VL). Few studies showing conflictive data about their efficacy and adverse events in pediatric population are available. This study aimed to evaluate efficacy and safety of amphotericin B deoxycholate vs. that of N-methylglucamine antimoniate in treating pediatric VL in Brazil. This was a randomized, open-label, 2-arm and controlled pilot clinical trial. Treatment naïve children and adolescents with VL without signs of severe illness were treated with N-methylglucamine antimoniate or amphotericin B deoxycholate. All patients were diagnosed with positive direct examination and/or positive PCR for Leishmania spp. performed in bone marrow samples. The primary efficacy end-point was VL cure determined after 180 days of completion of treatment. The analysis was performed using intention-to-treat (ITT) and per protocol (PP) analyses.

Eligibility criteria: Inclusion Criteria:

* Clinical symptoms of visceral leishmaniasis: fever plus hepatomegaly or splenomegaly
* Diagnosis of visceral leishmaniasis confirmed through parasite visualization in bone marrow smears or positive serology (indirect immunofluorescent antibody test or rK39 rapid test)or positive kDNA PCR test

Exclusion Criteria:

* Any of the following laboratory findings

  * Total serum bilirubin higher than 2,5 mg/dL
  * Serum SGOT higher than 5 times the upper normal level
  * Serum SGPT higher than 5 times the upper normal level
  * Prothrombin time concentration lower than 70%
  * Abnormal serum creatinine
* Any of the following signs or symptoms

  * Generalized edema
  * Severe malnutrition
  * Systemic inflammatory response syndrome
* Any of the following conditions

  * HIV infection/disease
  * Diabetes
  * Corticoid or immunosuppressive drugs use
  * Symptomatic heart diseases
  * Chronic hepatic or renal diseases
  * Lupus erythematosus

Primary outcomes:
measure: Cure rate
timeFrame: 3 months
Secondary outcomes:
measure: Improvement rate
timeFrame: 30 days
measure: Adverse events rate
timeFrame: 30 days
Other outcomes:
Locations:
city: Araguaína
country: Brazil
facility: Hospital de Doenças Tropicais
state: Tocantins
city: Palmas
country: Brazil
facility: Hospital Dona Regina
state: Tocantins
Study officials:
affiliation: Federal University of Tocantins
name: Myrlena RM Borges, MsC
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Brasilia
name: Gustavo AS Romero, PhD
role: STUDY_CHAIR
References:
citation: Borges MM, Pranchevicius MC, Noronha EF, Romero GA, Carranza-Tamayo CO. Efficacy and safety of amphotericin B deoxycholate versus N-methylglucamine antimoniate in pediatric visceral leishmaniasis: an open-label, randomized, and controlled pilot trial in Brazil. Rev Soc Bras Med Trop. 2017 Jan-Feb;50(1):67-74. doi: 10.1590/0037-8682-0455-2016.