Younis, Brima Musa, Mudawi Musa, Ahmed, Monnerat, Severine, Saeed, Mohammed Abdelrahim, Khalil, Eltahir Awad Gasim, Ahmed, Anas Elbashir, Ali, Mujahid Ahmed, Noureldin, Ali, Ouattara, Gina Muthoni, Nyakaya, Godfrey M., Teshome, Samuel, Omollo, Truphosa, Ochieng, Michael, Egondi, Thaddaeus, Mmbone, Mildred, Chu, Wan-Yu, Dorlo, Thomas, Zijlstra, Eduard E., Wasunna, Monique, Alvar, Jorge, Alves, Fabiana, Younis, Brima Musa, Mudawi Musa, Ahmed, Monnerat, Severine, Saeed, Mohammed Abdelrahim, Khalil, Eltahir Awad Gasim, Ahmed, Anas Elbashir, Ali, Mujahid Ahmed, Noureldin, Ali, Ouattara, Gina Muthoni, Nyakaya, Godfrey M., Teshome, Samuel, Omollo, Truphosa, Ochieng, Michael, Egondi, Thaddaeus, Mmbone, Mildred, Chu, Wan-Yu, Dorlo, Thomas, Zijlstra, Eduard E., Wasunna, Monique, Alvar, Jorge, and Alves, Fabiana
Background: Treatment for post-kala-azar dermal leishmaniasis (PKDL) in Sudan is currently recommended only for patients with persistent or severe disease, mainly because of the limitations of current therapies, namely toxicity and long hospitalization. We assessed the safety and efficacy of miltefosine combined with paromomycin and liposomal amphotericin B (LAmB) for the treatment of PKDL in Sudan. Methodology/principal findings: An open-label, phase II, randomized, parallel-arm, non-comparative trial was conducted in patients with persistent (stable or progressive disease for >= 6 months) or grade 3 PKDL, aged 6 to <= 60 years in Sudan. The median age was 9.0 years (IQR 7.0-10.0y) and 64% of patients were <= 12 years old. Patients were randomly assigned to either daily intra-muscular paromomycin (20mg/kg, 14 days) plus oral miltefosine (allometric dose, 42 days)-PM/MF-or LAmB (total dose of 20mg/kg, administered in four injections in week one) and oral miltefosine (allometric dose, 28 days)-AmB/MF. The primary endpoint was a definitive cure at 12 months after treatment onset, defined as clinical cure (100% lesion resolution) and no additional PKDL treatment between end of therapy and 12-month follow-up assessment. 104/110 patients completed the trial. Definitive cure at 12 months was achieved in 54/55 (98.2%, 95% CI 90.3-100) and 44/55 (80.0%, 95% CI 70.2-91.9) of patients in the PM/MF and AmB/MF arms, respectively, in the mITT set (all randomized patients receiving at least one dose of treatment; in case of error of treatment allocation, the actual treatment received was used in the analysis). No SAEs or deaths were reported, and most AEs were mild or moderate. At least one adverse drug reaction (ADR) was reported in 13/55 (23.6%) patients in arm 1 and 28/55 (50.9%) in arm 2, the most frequent being miltefosine-related vomiting and nausea, and LAmB-related hypokalaemia; no ocular or auditory ADRs were reported. Conclusions/significance: The PM/MF regimen