Treatment of Gastro-Intestinal and/or Hepatic Graft Versus Host Disease With Budesonide in Patients Following Peripheral Blood Stem Cell Transplantation
|First Received Date ICMJE||August 9, 2005|
|Last Updated Date||August 26, 2005|
|Start Date ICMJE||January 2001|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00128739 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Treatment of Gastro-Intestinal and/or Hepatic Graft Versus Host Disease With Budesonide in Patients Following Peripheral Blood Stem Cell Transplantation|
|Official Title ICMJE||A Phase 3 Study to Evaluate the Place of Budesonide in the Treatment of GVHD|
Twenty-four (2 x 12) patients with intestinal graft versus host disease (GVHD) Grades 2, 3 or 4 will be treated with budesonide 3mg three times daily or placebo for 12 weeks. All of the patients will receive cyclosporine and by mouth (po) prednisone or intravenous (IV) methylprednisone with a starting dose of 2mg/kg/day (standard anti-GVHD treatment). Doses of steroids will be decreased by approximately 10% or 10mg per week (depending upon patient’s weight) upon response to therapy, defined as a decrease of volume of diarrhea by 50% per day, decrease in abdominal pain and no presence of bloody stool. Patients with Grades 3 or 4 will be withdrawn from the study if there is no response after one week of therapy. Patients with Grade 2 may continue with no decrease in prednisone dose until response is achieved.
Graft versus host disease (GVHD) is one of the most common complications of bone marrow transplantation (BMT). Targets of GVHD are the gastro-intestinal tract (GIT) liver and skin, causing severe diarrhea and mucosal aberration and hepatitis that can cause life threatening liver failure. As a result of the mucosal aberration and the general immuno-suppression, caused both by the GVHD process itself and by the anti GVHD therapy, these patients are highly susceptible for severe, life threatening infections that usually originate from the GIT. Systemic steroids are the backbone of anti GVHD therapy. However, in GVHD systemic steroids have to be administered for a prolonged duration and in high doses, thus causing prolonged immune suppression, and exposing the patients to steroid side effects such as hypertension, diabetes, cataract formation etc.
Budesonide is a steroid that combines topical anti-inflammatory activity with high first-pass hepatic extraction. It was shown to be effective in treatment of inflammatory bowel disease with results slightly less then systemic steroids and fewer steroid-related adverse reactions. Except for its influence on the gut, budesonide was also shown to benefit inflammatory hepatic conditions such as primary biliary cirrhosis, liver transplantation and autoimmune hepatitis. Recently, it has been shown that budesonide is an effective treatment in acute GIT GVHD. The investigators propose to evaluate the effect of budesonide in GIT and hepatic GVHD with the following study.
Twelve patients after allogenic peripheral blood stem cell transplantation (PBSCT) with grade >= 2 GIT and/or hepatic GVHD will be prospectively compared to 12 placebo controls.
All patients will be assessed for GVHD scoring (organ and general) according to standard criteria and tested before inclusion for the following parameters –
After inclusion the patients will be treated with budesonide 9 or 15mg per day in divided doses or placebo. Other anti-GVHD treatment or ursodeoxycholic acid will not be withheld but tapering off will be tried.
Study duration: 14 weeks.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 3|
|Study Design ICMJE||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Primary Purpose: Treatment
|Condition ICMJE||Graft Vs Host Disease|
|Intervention ICMJE||Drug: Budesonide|
|Study Arm (s)||Not Provided|
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||August 2005|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||18 Years to 70 Years|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||Israel|
|NCT Number ICMJE||NCT00128739|
|Other Study ID Numbers ICMJE||25-23/02/01|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||Rafa Laboratories|
|Collaborators ICMJE||Dr. Falk Pharma GmbH|
|Information Provided By||Rafa Laboratories|
|Verification Date||August 2005|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP