title: Randomised, double-blind, placebo-controlled trial of oral budesonide for prophylaxis of acute intestinal graft-versus-host disease after allogeneic stem cell transplantation (PROGAST).
abstract: 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, number NCT00180089.
  
  
  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.
authors.forename: Renate
authors.initials: R
authors.lastname: Schmelz
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
authors.forename: Johannes
authors.initials: J
authors.lastname: Schetelig
authors.forename: Alexander
authors.initials: A
authors.lastname: Kiani
authors.forename: Uwe
authors.initials: U
authors.lastname: Platzbecker
authors.forename: Uta
authors.initials: U
authors.lastname: Schwanebeck
authors.forename: Xina
authors.initials: X
authors.lastname: Grählert
authors.forename: Lutz
authors.initials: L
authors.lastname: Uharek
authors.forename: Daniela
authors.initials: D
authors.lastname: Aust
authors.forename: Gustavo
authors.initials: G
authors.lastname: Baretton
authors.forename: Rainer
authors.initials: R
authors.lastname: Schwerdtfeger
authors.forename: Jochen
authors.initials: J
authors.lastname: Hampe
authors.forename: Roland
authors.initials: R
authors.lastname: Greinwald
authors.forename: Ralph
authors.initials: R
authors.lastname: Mueller
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.forename: Stephan
authors.initials: S
authors.lastname: Miehlke
mesh_terms: D000284:Administration, Oral; D019819:Budesonide / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005767:Gastrointestinal Diseases / Q000517:prevention & control*; D006086:Graft vs Host Disease / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged
chemical_list: D007166:Immunosuppressive Agents; D019819:Budesonide