ABSTRACT
BACKGROUND: There is insufficient evidence to support visceral leishmaniasis (VL) treatment recommendations in Brazil and an urgent need to improve current treatments. Drug combinations may be an option. METHODS: A multicenter, randomized, open label, controlled trial was conducted in five sites in Brazil to evaluate efficacy and safety of (i) amphotericin B deoxycholate (AmphoB) (1 mg/kg/day for 14 days), (ii) liposomal amphotericin B (LAMB) (3 mg/kg/day for 7 days) and (iii) a combination of LAMB (10 mg/kg single dose) plus meglumine antimoniate (MA) (20 mg Sb+5/kg/day for 10 days), compared to (iv) standard treatment with MA (20 mg Sb+5/kg/day for 20 days). Patients, aged 6 months to 50 years, with confirmed VL and without HIV infection were enrolled in the study. Primary efficacy endpoint was clinical cure at 6 months. A planned efficacy and safety interim analysis led to trial interruption. RESULTS: 378 patients were randomized to the four treatment arms: MA (n = 112), AmphoB (n = 45), LAMB (n = 109), or LAMB plus MA (n = 112). A high toxicity of AmphoB prompted an unplanned interim safety analysis and this treatment arm was dropped. Per intention-to-treat protocol final analyses of the remaining 332 patients show cure rates at 6 months of 77.5% for MA, 87.2% for LAMB, and 83.9% for LAMB plus MA, without statistically significant differences between the experimental arms and comparator (LAMB: 9.7%; CI95% -0.28 to 19.68, p = 0.06; LAMB plus MA: 6.4%; CI95% -3.93 to 16.73; p = 0.222). LAMB monotherapy was safer than MA regarding frequency of treatment-related adverse events (AE) (p = 0.045), proportion of patients presenting at least one severe AE (p = 0.029), and the proportion of AEs resulting in definitive treatment discontinuation (p = 0.003). CONCLUSIONS: Due to lower toxicity and acceptable efficacy, LAMB would be a more suitable first line treatment for VL than standard treatment. ClinicalTrials.gov identification number: NCT01310738. TRIAL REGISTRATION: ClinicalTrials.gov NCT01310738.
Subject(s)
Amphotericin B/therapeutic use , Antiprotozoal Agents/therapeutic use , Leishmaniasis, Visceral/drug therapy , Meglumine/therapeutic use , Organometallic Compounds/therapeutic use , Adolescent , Adult , Amphotericin B/adverse effects , Antiprotozoal Agents/adverse effects , Brazil , Child , Child, Preschool , Drug Therapy, Combination/methods , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/pathology , Female , Humans , Infant , Male , Meglumine/adverse effects , Meglumine Antimoniate , Middle Aged , Organometallic Compounds/adverse effects , Treatment Outcome , Young AdultABSTRACT
OBJECTIVE: This study aims evaluate the treatment of congenital heart disease conducted from 2000 to 2009. METHODS: The sample consisted of all patients undergoing surgical correction for congenital heart disease for ten years in Sergipe, Brazil. The patients were operated in three hospitals located in the city of Aracaju, capital of the state of Sergipe (Brazil). The study was divided into two periods defined by the start date of centralization of surgery. The variables collected were: age, sex, postoperative diagnosis, destination, type of surgery and hospital where the procedure was performed and the classification RACHS -1. RESULTS: In the period I, the estimate deficit of surgery was 69% decrease occurring in the period II to 55.3%. The postoperative diagnosis was more frequent closure of the interventricular communication (20.5%), closure of patent ductus arteriosus (20.2%) and atrial septal defect (19%). There was a statistically significant correlation between the expected mortality RACHS-1 and observed in the sample. The evaluation of RACHS-1 as a predictor of hospital mortality by ROC curve showed area of 0.860 95% CI 0.818 to 0.902 with P <0.0001. CONCLUSION: The results of this study indicate that the centralization and organization of existing resources are needed to improve the performance of surgical correction of congenital heart diseases.
