Comparative Effect of Proton Pump Inhibitors and Gastric Mucosal Protective Agents on Acute Graft-versus-Host Disease Post-Transplantation: A Prospective Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 198
- 试验地点
- 1
- 主要终点
- Incidence of acute graft-versus-host disease (aGVHD) post-transplantation
研究概览
简要总结
The goal of this clinical trial is to observe whether different gastric protection strategies affect the incidence of acute graft-versus-host disease (aGVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Proton pump inhibitors (PPIs) are routinely used for gastric protection during transplantation, but their prolonged use may suppress gastric acid, alter gut microbiota, and potentially increase the risk of aGVHD. Teprenone, a gastric mucosal protective agent (GMPA), enhances mucosal defense mechanisms including promoting mucus secretion, increasing gastric mucosal blood flow, and facilitating epithelial cell repair, without affecting gastric acid secretion, and may therefore preserve microbial diversity and modify aGVHD risk. This study compares two strategies: continuous PPI use versus switching from PPIs to teprenone after transplantation.
The main questions this study aims to answer are:
- Does switching from PPIs to teprenone after transplantation reduce the cumulative incidence of aGVHD within +100 days post-transplantation compared with continuous PPI use?
- What adverse events do participants experience with teprenone versus continuous PPI therapy?
- Does teprenone therapy provide better preservation of gut microbial diversity and lower rates of gastrointestinal and infectious complications compared with continuous PPI use?
In this prospective, randomized, parallel-controlled, single-center trial, approximately 198 patients undergoing allo-HSCT will be enrolled and assigned in a 1:1 ratio using a central randomization system. The experimental group (teprenone group) will receive standard-dose PPIs (esomeprazole, 40 mg/d, intravenous/oral) during conditioning and switch to teprenone (50 mg tid, orally) after transplantation through day +100. The control group (PPI group) will receive continuous standard-dose PPIs from conditioning through day +100. Probiotic use is prohibited from conditioning through day +100 in both groups. All other anti-infective, GVHD prophylaxis, and supportive care regimens are identical between the two groups.
The primary endpoint of this study is the cumulative incidence of aGVHD within +100 days post-transplantation. Secondary endpoints include grade II-IV and grade III-IV aGVHD, lower gastrointestinal aGVHD, steroid-refractory aGVHD, gut and salivary microbiome dynamics (α-diversity, β-diversity, and specific taxa at pre-conditioning, day 0, day +14, and day +28), plasma biomarkers related to intestinal barrier integrity, systemic inflammation, and immune regulation , infectious and gastrointestinal complications (febrile neutropenia, diarrhea, C. difficile infection, bacteremia, EBV/CMV reactivation, upper GI bleeding, reflux), and 1-year survival outcomes (non-relapse mortality, overall survival, GVHD-free/relapse-free survival).
During the study, participants will:
- Receive the assigned gastric protection regimen (teprenone or PPI) according to randomization
- Undergo regular assessments for safety and efficacy monitoring, including aGVHD surveillance and infection screening
- Provide fecal and saliva samples at pre-conditioning, day 0, day +14, and day +28 post-transplantation for microbiome analysis
- Provide peripheral blood samples at pre-conditioning, day 0, day +14, and day +28 post-transplantation for exploratory analysis
- Be followed for up to 1 year post-transplantation
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
- 12 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 12-70 years;
- •First allogeneic haploidentical HSCT for hematological malignancy;
- •Treated with a standardized myeloablative conditioning and GVHD prophylaxis regimen;
- •ECOG performance status ≤2 prior to transplant;
- •Written informed consent obtained.
排除标准
- •Pre-existing conditions requiring continuous PPI therapy prior to transplant, including severe reflux esophagitis, Zollinger-Ellison syndrome, active peptic ulcer with bleeding, or long-term use of dual antiplatelet agents or oral anticoagulants;
- •Known active, untreated Helicobacter pylori infection prior to transplant;
- •Active infectious enteritis or Clostridioides difficile infection prior to transplant;
- •Use of systemic broad-spectrum antibiotics within 7 days prior to transplant;
- •Use of probiotics within 14 days prior to transplant;
- •Planned total enteral nutrition or oral glutamine supplementation during the study period;
- •Planned parenteral nutrition for ≥7 consecutive days;
- •Inability to provide saliva or stool samples for collection;
- •Pregnant or lactating women;
- •History of significant neurological or psychiatric disorders (e.g., epilepsy, dementia) that may interfere with study participation;
- •Life expectancy <3 months or severe end-organ dysfunction;
- •Any other condition that, in the investigator's judgment, may compromise patient safety, compliance, or the validity of study results.
研究组 & 干预措施
PPI Group
Participants in this arm will receive continuous standard-dose proton pump inhibitor (PPI) therapy with esomeprazole at 40 mg daily, administered either intravenously or orally, from the start of conditioning through day +100 post-transplantation.
干预措施: Esomeprazole (Drug)
GMPA group
Participants in this arm will receive standard-dose proton pump inhibitor (PPI) during the conditioning phase. After transplantation, they will switch to teprenone, a gastric mucosal protective agent, at a dose of 50 mg three times daily (tid), administered orally, from the day of stem cell infusion through day +100 post-transplantation.
干预措施: Teprenone (Drug)
结局指标
主要结局
Incidence of acute graft-versus-host disease (aGVHD) post-transplantation
时间窗: From Day 0 to Day +100 post-transplantation, or until death or loss to follow-up, whichever came first
次要结局
- 1-year overall survival (OS)(From Day 0 to 1 year post-transplantation)
- Incidence of grade III-IV acute graft-versus-host disease (aGVHD)(From Day 0 to Day +100 post-transplantation, or until death or loss to follow-up, whichever came first)
- Incidence of grade II-IV acute graft-versus-host disease (aGVHD)(From Day 0 to Day +100 post-transplantation, or until death or loss to follow-up, whichever came first)
- Incidence of lower gastrointestinal aGVHD(From Day 0 to Day +100 post-transplantation, or until death or loss to follow-up, whichever came first)
- Oral microbiome diversity and composition(At pre-conditioning, Day +0, Day +14, and Day +28 post-transplantation)
- Fecal microbiome diversity and composition(At pre-conditioning, Day +0, Day +14, and Day +28 post-transplantation)
- Incidence of febrile neutropenia(From Day 0 to Day +100 post-transplantation, or until death or loss to follow-up, whichever came first)
- Incidence of diarrhea(From Day 0 to Day +100 post-transplantation, or until death or loss to follow-up, whichever came first)
- Incidence of Clostridioides difficile infection(From Day 0 to Day +100 post-transplantation, or until death or loss to follow-up)
- Incidence of enterococcal colonization/infection(From Day 0 to Day +100 post-transplantation, or until death or loss to follow-up, whichever came first)
- Incidence of bacteremia(From Day 0 to Day +100 post-transplantation, or until death or loss to follow-up, whichever came first)
- Incidence of upper gastrointestinal bleeding(From Day 0 to Day +100 post-transplantation, or until death or loss to follow-up, whichever came first)
- Incidence of clinically significant reflux symptoms(From Day 0 to Day +100 post-transplantation, or until death or loss to follow-up, whichever came first)
- 1-year non-relapse mortality (NRM)(From Day 0 to 1 year post-transplantation)
- 1-year GVHD-free, relapse-free survival (GRFS)(From Day 0 to 1 year post-transplantation)
研究者
Yanmin Zhao
Vice Director, Bone Marrow Transplantation Center, the First Affiliated Hospital, School of Medicine, Zhejiang University
First Affiliated Hospital of Zhejiang University