Trial Outcomes & Findings for Budesonide for Liver Transplant Immune Suppression (NCT NCT03304626)
NCT ID: NCT03304626
Last Updated: 2021-07-20
Results Overview
Acute Cellular Rejection of liver graft was determined by liver biopsy using Banff criteria. The decision to perform liver biopsy was as per treating physician based on patient's clinical course and blood chemisteries. Protocol bioopsies were not performed.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
40 participants
Primary outcome timeframe
Post-Transplant day 4 to week 24
Results posted on
2021-07-20
Participant Flow
Participant milestones
| Measure |
Study Group
Budesonide EC 3 mg capsule. The dose will be as follows
Time post Liver Transplantation Immunosuppressive therapy Days 0-3 Standard immune suppression (SIS) + Intravenous corticosteroids Days 4-30 SIS + Budesonide 9 mg Days 31-45 SIS + Budesonide 6 mg Days 46-90 SIS + Budesonide 3 mg Days 90 onwards SIS1
Budesonide 3Mg Capsule: Budesonide capsule in place of prednisone (standard of care)
|
Control Group
Standard of Care Controls that received
Time post Liver Transplantation Immunosuppressive therapy Days 0-3 Standard immune suppression (SIS) + Intravenous corticosteroids Days 4-30 SIS + Prednisone 15-60 mg Days 31-45 SIS + Prednisone 10 mg Days 46-90 SIS + Prednisone 2.5 to 7.5 mg Days 90 onwards SIS
|
|---|---|---|
|
Overall Study
STARTED
|
20
|
20
|
|
Overall Study
COMPLETED
|
18
|
19
|
|
Overall Study
NOT COMPLETED
|
2
|
1
|
Reasons for withdrawal
| Measure |
Study Group
Budesonide EC 3 mg capsule. The dose will be as follows
Time post Liver Transplantation Immunosuppressive therapy Days 0-3 Standard immune suppression (SIS) + Intravenous corticosteroids Days 4-30 SIS + Budesonide 9 mg Days 31-45 SIS + Budesonide 6 mg Days 46-90 SIS + Budesonide 3 mg Days 90 onwards SIS1
Budesonide 3Mg Capsule: Budesonide capsule in place of prednisone (standard of care)
|
Control Group
Standard of Care Controls that received
Time post Liver Transplantation Immunosuppressive therapy Days 0-3 Standard immune suppression (SIS) + Intravenous corticosteroids Days 4-30 SIS + Prednisone 15-60 mg Days 31-45 SIS + Prednisone 10 mg Days 46-90 SIS + Prednisone 2.5 to 7.5 mg Days 90 onwards SIS
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
|
Overall Study
Lack of Efficacy
|
1
|
1
|
Baseline Characteristics
Budesonide for Liver Transplant Immune Suppression
Baseline characteristics by cohort
| Measure |
Study Group
n=20 Participants
Budesonide EC 3 mg capsule. The dose will be as follows
Time post Liver Transplantation Immunosuppressive therapy Days 0-3 Standard immune suppression (SIS) + Intravenous corticosteroids Days 4-30 SIS + Budesonide 9 mg Days 31-45 SIS + Budesonide 6 mg Days 46-90 SIS + Budesonide 3 mg Days 90 onwards SIS1
Budesonide 3Mg Capsule: Budesonide capsule in place of prednisone (standard of care)
|
Control Group
n=20 Participants
Time post Liver Transplantation Immunosuppressive therapy Days 0-3 Standard immune suppression (SIS) + Intravenous corticosteroids Days 4-30 SIS + Prednisone 15-60 mg Days 31-45 SIS + Prednisone 10 mg Days 46-90 SIS + Prednisone 2.5 to 7.5 mg Days 90 onwards SIS
|
Total
n=40 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
20 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
57 years
n=5 Participants
|
56 years
n=7 Participants
|
56 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
19 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
17 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
20 participants
n=5 Participants
|
20 participants
n=7 Participants
|
40 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Post-Transplant day 4 to week 24Acute Cellular Rejection of liver graft was determined by liver biopsy using Banff criteria. The decision to perform liver biopsy was as per treating physician based on patient's clinical course and blood chemisteries. Protocol bioopsies were not performed.
Outcome measures
| Measure |
Study Group
n=20 Participants
Budesonide EC 3 mg capsule. The dose will be as follows
Time post Liver Transplantation Immunosuppressive therapy Days 0-3 Standard immune suppression (SIS) + Intravenous corticosteroids Days 4-30 SIS + Budesonide 9 mg Days 31-45 SIS + Budesonide 6 mg Days 46-90 SIS + Budesonide 3 mg Days 90 onwards SIS1
Budesonide 3Mg Capsule: Budesonide capsule in place of prednisone (standard of care)
|
Control Group
n=20 Participants
Standard of Care
Time post Liver Transplantation Immunosuppressive therapy Days 0-3 Standard immune suppression (SIS) + Intravenous corticosteroids Days 4-30 SIS + Prednisone 15-60 mg Days 31-45 SIS + Prednisone 10 mg Days 46-90 SIS + Prednisone 2.5 to 7.5 mg Days 90 onwards SIS
Standard of Care Prednisone: Prednisone taper (Standard of Care)
|
|---|---|---|
|
Number of Participants With Acute Cellular Rejection Between Study and Control Groups
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Post-Transplant day 4 to week 24Rates of new onset diabetes in patients who did not have diabetes prior to liver transplant
Outcome measures
| Measure |
Study Group
n=20 Participants
Budesonide EC 3 mg capsule. The dose will be as follows
Time post Liver Transplantation Immunosuppressive therapy Days 0-3 Standard immune suppression (SIS) + Intravenous corticosteroids Days 4-30 SIS + Budesonide 9 mg Days 31-45 SIS + Budesonide 6 mg Days 46-90 SIS + Budesonide 3 mg Days 90 onwards SIS1
Budesonide 3Mg Capsule: Budesonide capsule in place of prednisone (standard of care)
|
Control Group
n=20 Participants
Standard of Care
Time post Liver Transplantation Immunosuppressive therapy Days 0-3 Standard immune suppression (SIS) + Intravenous corticosteroids Days 4-30 SIS + Prednisone 15-60 mg Days 31-45 SIS + Prednisone 10 mg Days 46-90 SIS + Prednisone 2.5 to 7.5 mg Days 90 onwards SIS
Standard of Care Prednisone: Prednisone taper (Standard of Care)
|
|---|---|---|
|
Rate of New Onset Diabetes After Transplant
|
0 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: Post-Transplant week 12Population: This outcome was measured in study group only due to limited size and budget of the study
This outcomes was measured in Budesonide group only. Serum cortisol levels after 12 weeks of Budesonide use were checked to see if they fall below the adrenal suppression threshold of 3microgram/dl. If these were below 3 microgram/dl then patient is considered to have developed adrenal suppression. Second measure used to check for adrenal suppression was Cosyntorpin stimulation test. One-time, low-dose, cosyntropin stimulation test at week 12 was performed by administering cosyntropin at a dose of 0.5 µg/1.73 m2 of the body surface area and checking the serum cortisol levels at baseline and at 30 minutes after cosyntropin injection. A serum cortisol value of \<11 µg/dL after cosyntropin stimulation was used to define adrenal suppression. Participant meeting any of these criteria was said to have developed adrenal suppression
Outcome measures
| Measure |
Study Group
n=15 Participants
Budesonide EC 3 mg capsule. The dose will be as follows
Time post Liver Transplantation Immunosuppressive therapy Days 0-3 Standard immune suppression (SIS) + Intravenous corticosteroids Days 4-30 SIS + Budesonide 9 mg Days 31-45 SIS + Budesonide 6 mg Days 46-90 SIS + Budesonide 3 mg Days 90 onwards SIS1
Budesonide 3Mg Capsule: Budesonide capsule in place of prednisone (standard of care)
|
Control Group
Standard of Care
Time post Liver Transplantation Immunosuppressive therapy Days 0-3 Standard immune suppression (SIS) + Intravenous corticosteroids Days 4-30 SIS + Prednisone 15-60 mg Days 31-45 SIS + Prednisone 10 mg Days 46-90 SIS + Prednisone 2.5 to 7.5 mg Days 90 onwards SIS
Standard of Care Prednisone: Prednisone taper (Standard of Care)
|
|---|---|---|
|
Number of Participants With Adrenal Suppression
|
2 Participants
|
—
|
SECONDARY outcome
Timeframe: Post-Transplant day 4 to week 24Rates of adverse events 1. All cause mortality 2. Graft failure 3. Acute cellular rejection 4. New Onset Diabetes after Transplant 5. Rates of bacterial, fungal or viral infections 6. Other adverse events including ascites, pleural effusion, kidney injury, biliary stricture
Outcome measures
| Measure |
Study Group
n=20 Participants
Budesonide EC 3 mg capsule. The dose will be as follows
Time post Liver Transplantation Immunosuppressive therapy Days 0-3 Standard immune suppression (SIS) + Intravenous corticosteroids Days 4-30 SIS + Budesonide 9 mg Days 31-45 SIS + Budesonide 6 mg Days 46-90 SIS + Budesonide 3 mg Days 90 onwards SIS1
Budesonide 3Mg Capsule: Budesonide capsule in place of prednisone (standard of care)
|
Control Group
n=20 Participants
Standard of Care
Time post Liver Transplantation Immunosuppressive therapy Days 0-3 Standard immune suppression (SIS) + Intravenous corticosteroids Days 4-30 SIS + Prednisone 15-60 mg Days 31-45 SIS + Prednisone 10 mg Days 46-90 SIS + Prednisone 2.5 to 7.5 mg Days 90 onwards SIS
Standard of Care Prednisone: Prednisone taper (Standard of Care)
|
|---|---|---|
|
Number of Participants With Adverse Events
|
10 Participants
|
6 Participants
|
Adverse Events
Study Group
Serious events: 10 serious events
Other events: 2 other events
Deaths: 0 deaths
Control Group
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Study Group
n=20 participants at risk
Budesonide EC 3 mg capsule. The dose will be as follows
Time post Liver Transplantation Immunosuppressive therapy Days 0-3 Standard immune suppression (SIS) + Intravenous corticosteroids Days 4-30 SIS + Budesonide 9 mg Days 31-45 SIS + Budesonide 6 mg Days 46-90 SIS + Budesonide 3 mg Days 90 onwards SIS1
Budesonide 3Mg Capsule: Budesonide capsule in place of prednisone (standard of care)
|
Control Group
n=20 participants at risk
Standard of Care Controls that received
Time post Liver Transplantation Immunosuppressive therapy Days 0-3 Standard immune suppression (SIS) + Intravenous corticosteroids Days 4-30 SIS + Prednisone 15-60 mg Days 31-45 SIS + Prednisone 10 mg Days 46-90 SIS + Prednisone 2.5 to 7.5 mg Days 90 onwards SIS
|
|---|---|---|
|
Renal and urinary disorders
Acute Kidney injury
|
20.0%
4/20 • Number of events 4 • 6 months
Adverse events recorded in Standard of Care Control Arm were limited to 1. All cause mortality 2. Graft failure 3. Acute cellular rejection 4. New Onset Diabetes after Transplant 5. Rates of bacterial, fungal or viral infections
|
0.00%
0/20 • 6 months
Adverse events recorded in Standard of Care Control Arm were limited to 1. All cause mortality 2. Graft failure 3. Acute cellular rejection 4. New Onset Diabetes after Transplant 5. Rates of bacterial, fungal or viral infections
|
|
Gastrointestinal disorders
Ascites or Pleural effusion
|
15.0%
3/20 • Number of events 3 • 6 months
Adverse events recorded in Standard of Care Control Arm were limited to 1. All cause mortality 2. Graft failure 3. Acute cellular rejection 4. New Onset Diabetes after Transplant 5. Rates of bacterial, fungal or viral infections
|
0.00%
0/20 • 6 months
Adverse events recorded in Standard of Care Control Arm were limited to 1. All cause mortality 2. Graft failure 3. Acute cellular rejection 4. New Onset Diabetes after Transplant 5. Rates of bacterial, fungal or viral infections
|
|
Gastrointestinal disorders
Bile leak
|
5.0%
1/20 • Number of events 1 • 6 months
Adverse events recorded in Standard of Care Control Arm were limited to 1. All cause mortality 2. Graft failure 3. Acute cellular rejection 4. New Onset Diabetes after Transplant 5. Rates of bacterial, fungal or viral infections
|
0.00%
0/20 • 6 months
Adverse events recorded in Standard of Care Control Arm were limited to 1. All cause mortality 2. Graft failure 3. Acute cellular rejection 4. New Onset Diabetes after Transplant 5. Rates of bacterial, fungal or viral infections
|
|
Gastrointestinal disorders
Biliary stricture
|
5.0%
1/20 • Number of events 1 • 6 months
Adverse events recorded in Standard of Care Control Arm were limited to 1. All cause mortality 2. Graft failure 3. Acute cellular rejection 4. New Onset Diabetes after Transplant 5. Rates of bacterial, fungal or viral infections
|
0.00%
0/20 • 6 months
Adverse events recorded in Standard of Care Control Arm were limited to 1. All cause mortality 2. Graft failure 3. Acute cellular rejection 4. New Onset Diabetes after Transplant 5. Rates of bacterial, fungal or viral infections
|
|
Cardiac disorders
Sinus tachycardia
|
5.0%
1/20 • Number of events 1 • 6 months
Adverse events recorded in Standard of Care Control Arm were limited to 1. All cause mortality 2. Graft failure 3. Acute cellular rejection 4. New Onset Diabetes after Transplant 5. Rates of bacterial, fungal or viral infections
|
0.00%
0/20 • 6 months
Adverse events recorded in Standard of Care Control Arm were limited to 1. All cause mortality 2. Graft failure 3. Acute cellular rejection 4. New Onset Diabetes after Transplant 5. Rates of bacterial, fungal or viral infections
|
Other adverse events
| Measure |
Study Group
n=20 participants at risk
Budesonide EC 3 mg capsule. The dose will be as follows
Time post Liver Transplantation Immunosuppressive therapy Days 0-3 Standard immune suppression (SIS) + Intravenous corticosteroids Days 4-30 SIS + Budesonide 9 mg Days 31-45 SIS + Budesonide 6 mg Days 46-90 SIS + Budesonide 3 mg Days 90 onwards SIS1
Budesonide 3Mg Capsule: Budesonide capsule in place of prednisone (standard of care)
|
Control Group
n=20 participants at risk
Standard of Care Controls that received
Time post Liver Transplantation Immunosuppressive therapy Days 0-3 Standard immune suppression (SIS) + Intravenous corticosteroids Days 4-30 SIS + Prednisone 15-60 mg Days 31-45 SIS + Prednisone 10 mg Days 46-90 SIS + Prednisone 2.5 to 7.5 mg Days 90 onwards SIS
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
10.0%
2/20 • Number of events 2 • 6 months
Adverse events recorded in Standard of Care Control Arm were limited to 1. All cause mortality 2. Graft failure 3. Acute cellular rejection 4. New Onset Diabetes after Transplant 5. Rates of bacterial, fungal or viral infections
|
0.00%
0/20 • 6 months
Adverse events recorded in Standard of Care Control Arm were limited to 1. All cause mortality 2. Graft failure 3. Acute cellular rejection 4. New Onset Diabetes after Transplant 5. Rates of bacterial, fungal or viral infections
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place