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
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 142
- 主要终点
- Cumulative incidence of platelet engraftment at 2 months after transplantation
研究概览
简要总结
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 by 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 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 human leukocyte antigen (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
排除标准
- •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
研究组 & 干预措施
Control Group
Patients receive standard haploidentical hematopoietic stem cell transplantation and identical supportive treatments without prophylactic oral NAC throughout the study period.
Prophylactic N-acetylcysteine (NAC) Group
Patients receive oral NAC 400 mg three times daily from Day -14 before transplantation to Day +60 post-transplant, combined with standard haploidentical hematopoietic stem cell transplantation and routine supportive care.
干预措施: N-acetylcysteine (Drug)
结局指标
主要结局
Cumulative incidence of platelet engraftment at 2 months after transplantation
时间窗: 2 months post-HSCT
Platelet engraftment was characterized as the first day with a platelet count of at least 20 × 10\^9/L without transfusion support for seven consecutive days.
Cumulative incidence of platelet engraftment by 2 months after transplantation
时间窗: 2 months post-HSCT
Platelet engraftment was characterized as the first day with a platelet count of at least 20 × 10\^9/L without transfusion support for seven consecutive days.
次要结局
- Cumulative incidence of neutrophil engraftment at 2 months after transplantation(2 months post-HSCT)
- Incidence of poor hematopoietic reconstitution at 2 months post-transplant(2 months post-HSCT)
- Cumulative volume of blood product transfusions(From pre-transplant Day -14 to post-transplant Day +60)
- Cumulative incidence of acute and chronic graft-versus-host disease (GVHD)(100 days for aGVHD; 1 year for cGVHD after transplantation)
- 1-year overall survival (OS)(1 year after transplantation)
- 1-year graft-versus-host disease-free/failure-free survival (GFFS)(1 year after transplantation)
- Bone marrow endothelial progenitor cell (EPC) count and intracellular ROS level(Baseline (pre-transplant), post-transplant 1 months and 2 months)
- Cumulative incidence of neutrophil engraftment by 2 months after transplantation(2 months post-HSCT)
- Incidence of poor hematopoietic reconstitution by 2 months post-transplant(2 months post-HSCT)
- Cumulative incidence of acute and chronic graft-versus-host disease (aGVHD/cGVHD)(100 days for aGVHD; 1 year for cGVHD after transplantation)
- 1-year graft-versus-host disease-free, failure-free survival (GFFS)(1 year after transplantation)
- Bone marrow endothelial progenitor cell (EPC) count and intracellular reactive oxygen species (ROS) level(Baseline (pre-transplant), post-transplant 1 months and 2 months)
研究者
Xiao-Jun Huang
Professor
Peking University People's Hospital