GMPA Versus PPI for Gastric Protection and aGVHD Risk
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age12-70
SponsorFirst Affiliated Hospital of Zhejiang University
About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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;
Disqualifiers
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;
Trial design
Design model
Parallel
Treatments tested in this trial
Teprenone
DrugTeprenone acts by enhancing gastric mucosal defense mechanisms, including promoting mucus secretion, increasing gastric mucosal blood flow, and facilitating epithelial cell repair, without affecting gastric acid secretion. The switch from PPI to teprenone is intended to maintain gastric protection while potentially preserving gut microbial diversity and reducing the risk of acute graft-versus-host disease (aGVHD).
Esomeprazole
DrugContinuous PPI use suppresses gastric acid secretion throughout the peri-transplantation period, which may alter gut microbiota composition and potentially influence aGVHD risk.
Treatment groups
198 Participants
are divided into 2 treatment groupsGroup A: GMPA groupExperimental treatment 1 intervention
Group B: PPI GroupPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Incidence of acute graft-versus-host disease (aGVHD) post-transplantation
Time frame
From Day 0 to Day +100 post-transplantation, or until death or loss to follow-up, whichever came firstSecondary outcomes
1
Incidence of grade II-IV acute graft-versus-host disease (aGVHD)
Time frame
From Day 0 to Day +100 post-transplantation, or until death or loss to follow-up, whichever came first2
Incidence of grade III-IV acute graft-versus-host disease (aGVHD)
Time frame
From Day 0 to Day +100 post-transplantation, or until death or loss to follow-up, whichever came first3
Incidence of lower gastrointestinal aGVHD
Time frame
From Day 0 to Day +100 post-transplantation, or until death or loss to follow-up, whichever came first4
Oral microbiome diversity and composition
Time frame
At pre-conditioning, Day +0, Day +14, and Day +28 post-transplantationSponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov