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

Abstract

Introduction: 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. Methods: 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 (20mg/ kg/day for 20 days) or amphotericin B deoxycholate (1mg/kg/day for 14 days). 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. Results: In total, 101 volunteers were assessed. Efficacy was similar for both groups. The antimonial (n=51) and amphotericin B groups (n=50) had a cure rate of 94.1% and 100%, and 94% and 97.9% according to ITT and PP analyses, respectively. All patients reported adverse events (AE). Serious AE incidence was similar in both groups. Five individuals were excluded from the study because of severe adverse events. Conclusions: N-methylglucamine antimoniate and amphotericin B deoxycholate have similar efficacy and adverse events rate in pediatric patients with VL.

Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial

“…The choice of MA as the reference arm was based on the prevailing Brazilian VL treatment guidelines at the time when the study was started in 2011 [5], as well as data obtained from a clinical trial that had been concluded in 2009 [13]. AmphoB and LAMB regimens were included as these were routinely used in Brazil and had been included in 2011 into the new treatment guidelines to reduce the VL fatality rate [14].…”

“…AmphoB and LAMB regimens were included as these were routinely used in Brazil and had been included in 2011 into the new treatment guidelines to reduce the VL fatality rate [14]. The same regimen of AmphoB had also been used in the above-referenced clinical trial conducted in 2009 [13]. The selection of the combination therapy with LAMB single dose plus MA was based on the lack of local efficacy evidence for miltefosine and PM, and the satisfactory efficacy rates reported for MA, the first line treatment in the country.…”

Visceral leishmaniasis in a patient with ulcerative colitis: A case report

“…Published cases of fatal toxicity related to antimonials include severe toxic hepatitis and pancreatitis 7 , fatal arrhythmia 23 , and unexpected sudden death 20 . In pediatric patients, a recent trial showed that N-methylglucamine antimoniate (n = 51) and amphotericin B deoxycholate (n = 50) had similar cure rates (94.1% vs. 94%, respectively) and serious adverse events (SAE) incidence was similar in both groups 24 . Treatment may be complicated with drug interactions between antileishmanial and other administered medications and their coinciding toxicity 21 .…”

Treatment for human visceral leishmaniasis: a cost‐effectiveness analysis for Brazil

“…10 Obtained by the sum of the product of the multiplication of the cost of the meglumine antimoniate vial (US$ 1.30) by the number of vials per day [2] by the number of days of treatment [10], and the product of the multiplication of the cost of the liposomal amphotericin B vial (US$ 18.76) by the number of vials per day [8] by the number of days [1]. 11 Obtained by multiplying the average daily cost of hospitalisation (US$ 16.03) and the average duration of treatment (10.33 days). 12 Obtained by multiplying the daily wage loss (US$ 10.68) by the time of 25.33 days of absence from work (10.33 days of hospitalisation plus 15 days of home recovery).…”

“…Incidentally, the therapeutic arm evaluating AMBD in the study by Romero et al (2017) was suspended following the recommendation of the data safety monitoring board due to safety issues [10]. Also, the evidence on efficacy and safety of AMDB in Brazil is restricted to one clinical trial comparing AMBD with MA in children aged 6 months to 12 years [11]. Thus, the purpose of this study was to estimate the cost-effectiveness of strategies for the treatment of VL in Brazil to aid decision-making in the public health system.…”