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Abstract：
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.
RESULTS: 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 87% 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)-LAmB/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 PM/MF arm and 28/55 (50.9%) in LAmB/MF arm, the most frequent being miltefosine-related vomiting and nausea, and LAmB-related hypokalaemia; no ocular or auditory ADRs were reported.
CONCLUSIONS: The PM/MF regimen requires shorter hospitalization than the currently recommended 60-90-day treatment, and is safe and highly efficacious, even for patients with moderate and severe PKDL. It can be administered at primary health care facilities, with LAmB/MF as a good alternative. For future VL elimination, we need new, safe oral therapies for all patients with PKDL.
BACKGROUND: ClinicalTrials.gov NCT03399955, https://clinicaltrials.gov/study/NCT03399955 ClinicalTrials.gov ClinicalTrials.gov.
RESULTS: 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 87% 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)-LAmB/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 PM/MF arm and 28/55 (50.9%) in LAmB/MF arm, the most frequent being miltefosine-related vomiting and nausea, and LAmB-related hypokalaemia; no ocular or auditory ADRs were reported.
CONCLUSIONS: The PM/MF regimen requires shorter hospitalization than the currently recommended 60-90-day treatment, and is safe and highly efficacious, even for patients with moderate and severe PKDL. It can be administered at primary health care facilities, with LAmB/MF as a good alternative. For future VL elimination, we need new, safe oral therapies for all patients with PKDL.
BACKGROUND: ClinicalTrials.gov NCT03399955, https://clinicaltrials.gov/study/NCT03399955 ClinicalTrials.gov ClinicalTrials.gov.
摘要：
背景：苏丹黑热病后真皮利什曼病（PKDL）的治疗目前仅推荐用于患有持续性或严重疾病的患者，主要是因为目前疗法的局限性,即毒性和长期住院。我们评估了米替福辛联合巴龙霉素和脂质体两性霉素B（LAmB）治疗苏丹PKDL的安全性和有效性。
结果：开放标签，第二阶段,随机化，平行臂,非比较性试验是在持续性(稳定或进行性疾病≥6个月)或3级PKDL患者中进行的,苏丹6至≤60岁。中位年龄为9.0岁（IQR7.0-10.0y），64％的患者≤12岁。患者被随机分配至每日肌内巴龙霉素（20mg/kg，14天）加口服米替福辛（异速剂量，42天）-PM/MF-或LAmB（总剂量为20mg/kg，在第一周内四次注射给药)和口服米替福辛(异速剂量，28天）-AmB/MF。主要终点是治疗开始后12个月的最终治愈，定义为临床治愈（病变消退率100％），并且在治疗结束和12个月随访评估之间没有额外的PKDL治疗。104/110名患者完成了试验。12个月时的最终治愈在54/55中实现(98.2%，95%CI90.3-100）和44/55（80.0%，PM/MF和AmB/MF组患者的95%CI70.2-91.9)，分别,在mITT组中（所有接受至少一个剂量治疗的随机患者；在治疗分配错误的情况下，接受的实际治疗用于分析).没有报告SAE或死亡，大多数AE为轻度或中度。在第1组的13/55（23.6％）和第2组的28/55（50.9％）患者中至少报告了一种药物不良反应（ADR），最常见的是与米替福辛相关的呕吐和恶心。和LAmB相关的低钾血症;没有眼或听觉ADR的报告。
结论：PM/MF方案比目前推荐的60-90天治疗需要更短的住院时间，并且安全高效，即使是中度和重度PKDL患者。它可以在初级卫生保健机构进行管理，与LAmB/MF作为一个很好的选择。对于未来的VL消除，我们需要新的,所有PKDL患者的安全口服治疗。
背景：ClinicalTrials.govNCT03399955,https://clinicaltrials.gov/study/NCT03399955ClinicalTrials.govClinicalTrials.gov
结果：开放标签，第二阶段,随机化，平行臂,非比较性试验是在持续性(稳定或进行性疾病≥6个月)或3级PKDL患者中进行的,苏丹6至≤60岁。中位年龄为9.0岁（IQR7.0-10.0y），64％的患者≤12岁。患者被随机分配至每日肌内巴龙霉素（20mg/kg，14天）加口服米替福辛（异速剂量，42天）-PM/MF-或LAmB（总剂量为20mg/kg，在第一周内四次注射给药)和口服米替福辛(异速剂量，28天）-AmB/MF。主要终点是治疗开始后12个月的最终治愈，定义为临床治愈（病变消退率100％），并且在治疗结束和12个月随访评估之间没有额外的PKDL治疗。104/110名患者完成了试验。12个月时的最终治愈在54/55中实现(98.2%，95%CI90.3-100）和44/55（80.0%，PM/MF和AmB/MF组患者的95%CI70.2-91.9)，分别,在mITT组中（所有接受至少一个剂量治疗的随机患者；在治疗分配错误的情况下，接受的实际治疗用于分析).没有报告SAE或死亡，大多数AE为轻度或中度。在第1组的13/55（23.6％）和第2组的28/55（50.9％）患者中至少报告了一种药物不良反应（ADR），最常见的是与米替福辛相关的呕吐和恶心。和LAmB相关的低钾血症;没有眼或听觉ADR的报告。
结论：PM/MF方案比目前推荐的60-90天治疗需要更短的住院时间，并且安全高效，即使是中度和重度PKDL患者。它可以在初级卫生保健机构进行管理，与LAmB/MF作为一个很好的选择。对于未来的VL消除，我们需要新的,所有PKDL患者的安全口服治疗。
背景：ClinicalTrials.govNCT03399955,https://clinicaltrials.gov/study/NCT03399955ClinicalTrials.govClinicalTrials.gov
