Prophylactic NAC to Improve Platelet Engraftment After Haploidentical Transplantation in Severe Aplastic Anemia Patients

Официальное название

Prophylactic N-Acetylcysteine to Facilitate Platelet Engraftment Following Haploidentical Hematopoietic Stem Cell Transplantation for Patients With Severe Aplastic Anemia: A Prospective Multicenter Randomized Controlled Trial

Обзор

This study aims to evaluate the efficacy and safety of prophylactic oral N-acetylcysteine (NAC) for facilitating platelet engraftment in patients with severe aplastic anemia (SAA) receiving haploidentical hematopoietic stem cell transplantation (haplo-HSCT). This is a prospective, multicenter, randomized controlled trial enrolling a total of 142 patients with SAA scheduled for their first haplo-HSCT, who will be randomly assigned at a 1:1 ratio to the NAC prophylaxis group or the control group, with 71 subjects in each arm. Patients in the intervention group will receive oral NAC 400 mg three times daily from Day -14 before transplantation to Day +60 post-transplant, while the control group will receive no prophylactic NAC, with all other transplant-related treatments identical between the two groups. The primary endpoint is the cumulative platelet engraftment rate at 2 months after transplantation. Secondary endpoints cover neutrophil engraftment rate, incidence of poor hematopoietic reconstitution, cumulative blood product transfusion volume, graft-versus-host disease (GVHD), overall survival, GVHD-free and failure-free survival, and biomarkers reflecting bone marrow hematopoietic microenvironment reconstruction. Safety outcomes will be assessed via adverse events graded per NCI CTCAE Version 5.0. Statistical analyses will be performed using R 4.4.0 software, primarily adopting competing risk models and the Kaplan-Meier method based on full analysis set, per-protocol set and safety set. This trial will clarify intergroup differences in platelet recovery, other efficacy endpoints and safety profiles, verify the clinical benefits and safety of NAC, and generate high-quality clinical evidence for prophylactic intervention targeting platelet engraftment after haplo-HSCT in SAA patients to optimize clinical management strategies.

Вмешательства

• Препарат N-acetylcysteine
  Oral N-acetylcysteine capsules, 400 mg per dose, administered three times daily. Treatment starts at Day -14 before transplantation and continues until Day +60 after transplantation.

Первичные конечные точки

• Cumulative incidence of platelet engraftment at 2 months after transplantation [Срок оценки: 2 months post-HSCT]

Вторичные конечные точки (7)

• Cumulative incidence of neutrophil engraftment at 2 months after transplantation [Срок оценки: 2 months post-HSCT]
• Incidence of poor hematopoietic reconstitution at 2 months post-transplant [Срок оценки: 2 months post-HSCT]
• Cumulative volume of blood product transfusions [Срок оценки: From pre-transplant Day -14 to post-transplant Day +60]
• Cumulative incidence of acute and chronic graft-versus-host disease (GVHD) [Срок оценки: 100 days for aGVHD; 1 year for cGVHD after transplantation]
• 1-year overall survival (OS) [Срок оценки: 1 year after transplantation]
• 1-year graft-versus-host disease-free/failure-free survival (GFFS) [Срок оценки: 1 year after transplantation]
• Bone marrow endothelial progenitor cell (EPC) count and intracellular ROS level [Срок оценки: Baseline (pre-transplant), post-transplant 1 months and 2 months]

Критерии участия

Критерии включения

• Diagnosed with aplastic anemia and scheduled to receive first haplo-HSCT
• Aged 14 to 50 years
• Hematopoietic Cell Transplant Comorbidity Index (HCT-CI) ≤ 2
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Negative donor-specific HLA antibodies
• No uncontrolled active infection before transplantation
• No irreversible severe organ dysfunction
• Voluntarily sign written informed consent and agree to complete scheduled follow-up

Критерии исключения

• Confirmed allergy or hypersensitivity to NAC
• Medical history of bronchial asthma
• Uncontrolled severe psychiatric disorders unable to cooperate with treatment and follow-up
• Active peptic ulcer, gastrointestinal bleeding, inflammatory bowel disease or severe gastrointestinal dysfunction
• Female patients who are pregnant or breastfeeding

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07737262 · 2026PHD022-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗