Malavasi André, Ribeiro Camilla Moreira, Agati Leandro Barile, Silva Filho Agnaldo, Berger Charles, Schor Eduardo, Comin Ana, Bezerra Neto Eduardo José, Oliveira Taís Helena de, Caldas Polyana Raposo, Lopes Francisco, Westphalen Nathalia, Vieira Francisleny, Socca Eduardo Augusto Rabelo, Komar Daniele, Ramacciotti Eduardo
Department of Obstetrics and Gynecology, School of Medicine at, São Paulo State University (HC-FMUSP), São Paulo, SP, Brazil.
Science Valley Research Institute, Santo André-São Paulo, Brazil.
Ann Med. 2025 Dec;57(1):2527352. doi: 10.1080/07853890.2025.2527352. Epub 2025 Jul 11.
Pelvic pain secondary to endometriosis is a disabling condition. There are multiple treatments available, with variable endpoints. No prospective controlled studies were carried out evaluating subdermal pellets of gestrinone in this population.
One hundred participants with documented deep infiltrative endometriosis who underwent surgery without satisfactory response will be randomly assigned (1:1) to either gestrinone 85 mg subdermal bioabsorbable pellets or placebo. Both arms will receive levonorgestrel-releasing intrauterine system (LNG-IUS 12). The treatment duration will be 6 months, with baseline, 3 months and 6 months clinical visits. The primary endpoint is a combination of serious adverse events (SAEs) accumulated within 6 months of insertion of the gestrinone or placebo pellet and collected through spontaneous reports and clinical findings. They include death, threat or risk to life, need for hospitalization, prolongation of pre-existing hospitalization, permanent disability or damage, congenital anomaly; or significant medical occurrences such as venous thromboembolism. The primary safety outcome will be the percentage of patients who do not experience SAEs 6 months after randomization. Androgenization, changes in laboratory exams and in pelvic pain intensity as well as quality of life (SF-36 and EHP-30 questionnaires) will be further evaluated. Daily data on uterine bleeding patterns and the use of pain relief medication will be remotely collected using an App. Pharmacokinetics profile of gestrinone pellet will be characterized.
This is the first multicenter randomized controlled trial to evaluate the safety, tolerability and pharmacokinetics profile of subdermal gestrinone pellets and might inform clinical practice for treating these patients.
GLADE trial is registered at ClinicalTrials.gov (NCT05570786). This is an investigator-initiated research supported by Biòs Farmacêutica.
子宫内膜异位症继发盆腔疼痛是一种致残性疾病。有多种治疗方法可供选择，终点各异。此前未进行过前瞻性对照研究来评估炔诺酮皮下植入剂在该人群中的效果。
100名经记录患有深部浸润性子宫内膜异位症且手术效果不佳的参与者将被随机分配（1:1）至接受85毫克炔诺酮皮下可生物吸收植入剂或安慰剂治疗组。两组均接受左炔诺孕酮宫内节育系统（LNG-IUS 12）。治疗持续时间为6个月，在基线、3个月和6个月时进行临床访视。主要终点是在植入炔诺酮或安慰剂植入剂后6个月内累积的严重不良事件（SAE）组合，通过自发报告和临床检查收集。这些事件包括死亡、对生命的威胁或风险、住院需求、原有住院时间延长、永久性残疾或损害、先天性异常；或重大医疗事件，如静脉血栓栓塞。主要安全性结局将是随机分组后6个月未发生SAE的患者百分比。将进一步评估雄激素化、实验室检查变化、盆腔疼痛强度变化以及生活质量（SF-36和EHP-30问卷）。将使用应用程序远程收集关于子宫出血模式和止痛药物使用的每日数据。将对炔诺酮植入剂的药代动力学特征进行描述。
这是第一项评估皮下炔诺酮植入剂安全性、耐受性和药代动力学特征的多中心随机对照试验，可能为治疗这些患者的临床实践提供参考。
GLADE试验已在ClinicalTrials.gov注册（NCT05570786）。这是一项由Biòs Farmacêutica支持的研究者发起的研究。
