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

Stephan Miehlke³  Gerhard Ehninger⁶  Ralph Mueller⁵  Roland Greinwald⁵  Jochen Hampe⁶  Rainer Schwerdtfeger⁴  Gustavo Baretton¹  Daniela Aust¹  Lutz Uharek²  Xina Grählert⁷  Uta Schwanebeck⁷  Uwe Platzbecker⁶  Alexander Kiani⁶  Johannes Schetelig⁶  Martin Bornhäuser⁶  Renate Schmelz⁶ 

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

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

Others  :  1121755
DOI  :  10.1186/s12876-014-0197-7

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

【 摘 要 】

Background

Gastrointestinal 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.

Methods

In 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 webcite, 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.

Results

The 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.

Conclusions

Budesonide 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】

   
2014 Schmelz et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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