Randomised, double-blind, placebo-controlled trial of oral budesonide for prophylaxis of acute intestinal graft-versus-host disease after allogeneic stem cell transplantation (PROGAST)

BMC Gastroenterology

Research Article

Stephan Miehlke¹  Lutz Uharek²  Uta Schwanebeck³  Xina Grählert³  Rainer Schwerdtfeger⁴  Ralph Mueller⁵  Roland Greinwald⁵  Gerhard Ehninger⁶  Johannes Schetelig⁶  Uwe Platzbecker⁶  Renate Schmelz⁶  Jochen Hampe⁶  Alexander Kiani⁶  Martin Bornhäuser⁶  Daniela Aust⁷  Gustavo Baretton⁷ 

[1] Center for Digestive Diseases, Cooperation of Internal Medicine, Hamburg, Germany;Charité-Campus Benjamin Franklin, Medical Department 3, Berlin, Germany;Coordinating Centre for Clinical Trials, Dresden, Germany;Deutsche Klinik für Diagnostik, KMT Zentrum, Wiesbaden, Germany;Dr. Falk Pharma GmbH, Freiburg, Germany;Medical Department I, University Hospital Carl Gustav Carus, Fetscherstr. 74, 01307, Dresden, Germany;University Hospital Carl Gustav Carus, Institute for Pathology, Dresden, Germany;

关键词: Acute intestinal Graft-versus-host disease;    Prophylaxis;    Allogeneic stem cell transplantation;    Budesonide;   

DOI  :  10.1186/s12876-014-0197-7

 received in 2013-08-26, accepted in 2014-10-31,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundGastrointestinal graft–versus-host disease (GvHD) is a potentially life-threatening complication after allogeneic stem cell transplantation (SCT). Since therapeutic options are still limited, a prophylactic approach seems to be warranted.MethodsIn this randomised, double-blind-phase III trial, we evaluated the efficacy of budesonide in the prophylaxis of acute intestinal GvHD after SCT. The trial was registered at https://clinicaltrials.gov, number NCT00180089.Patients were randomly assigned to receive either 3 mg capsule three times daily oral budesonide or placebo. Budesonide was applied as a capsule with pH-modified release in the terminal ileum. Study medication was administered through day 56, follow-up continued until 12 months after transplantation. If any clinical signs of acute intestinal GvHD appeared, an ileocolonoscopy with biopsy specimens was performed.ResultsThe crude incidence of histological or clinical stage 3–4 acute intestinal GvHD until day 100 observed in 91 (n =48 budesonide, n =43 placebo) evaluable patients was 12.5% (95% CI 3-22%) under treatment with budesonide and 14% (95% CI 4-25%) under placebo (p = 0.888). Histologic and clinical stage 3–4 intestinal GvHD after 12 months occurred in 17% (95% CI 6-28%) of patients in the budesonide group and 19% (CI 7-32%) in the placebo group (p = 0.853). Although budesonide was tolerated well, we observed a trend towards a higher rate of infectious complications in the study group (47.9% versus 30.2%, p = 0.085). The cumulative incidences at 12 months of intestinal GvHD stage >2 with death as a competing event (budesonide 20.8% vs. placebo 32.6%, p = 0.250) and the cumulative incidence of relapse (budesonide 20.8% vs. placebo 16.3%, p = 0.547) and non-relapse mortality (budesonide 28% (95% CI 15-41%) vs. placebo 30% (95% CI 15-44%), showed no significant difference within the two groups (p = 0.911). The trial closed after 94 patients were enrolled because of slow accrual. Within the limits of the final sample size, we were unable to show any benefit for the addition of budesonide to standard GvHD prophylaxis.ConclusionsBudesonide did not decrease the occurrence of intestinal GvHD in this trial. These results imply most likely that prophylactic administration of budenoside with pH-modified release in the terminal ileum is not effective.

【 授权许可】

CC BY   
© Schmelz et al.; licensee BioMed Central Ltd. 2014