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