A-WISH: Gradual Withdrawal of Immune System Suppressing Drugs in Patients Receiving a Liver Transplant
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
Overall Status
Completed
CT.gov ID
NCT00135694
Collaborator
Immune Tolerance Network (ITN) (Other)
275
8
2
119
34.4
0.3
Study Details
Study Description
Brief Summary
In order to prevent organ rejection, patients receiving liver transplants currently require life-long treatment with immune system-suppressing medications to prevent the rejection of the transplanted liver. However, these medications can cause long-term side effects, such as infection, kidney problems, diabetes, and cancer. In patients infected with hepatitis C virus (HCV), these medications may increase the risk of HCV infection in the transplanted liver. The purpose of this study is to determine whether a slow withdrawal of immune system-suppressing medications is safe in two groups of subjects: those who receive a liver transplant due to HCV, and those who receive a liver transplant due to non-immune, non-viral causes of liver failure. The study will also look at whether slow withdrawal will help reduce the long-term side effects of immune system-suppressing medications and decrease the chance for HCV infection of the new liver in transplant patients with HCV.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This is a prospective multicenter, open-label, randomized trial in which individuals with liver failure due to hepatitis C or to nonimmune nonviral causes undergo liver transplantation and receive immunosuppression with a calcineurin inhibitor and corticosteroids. Corticosteroids are tapered in the 3 months after transplantation and the calcineurin inhibitor is continued. Participants are regularly assessed for evidence of allograft rejection. One year after transplantation, participants eligible for withdrawal are randomly assigned in a 4 to 1 ratio to immunosuppression withdrawal or to maintenance. Participants assigned to withdrawal undergo a scheduled taper over approximately 1 year.
Study Design
Study Type:
Interventional
Actual Enrollment
:
275 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Trial to Assess the Safety of Immunosuppression Withdrawal in Liver Transplant Recipients
Study Start Date
:
Oct 1, 2005
Actual Primary Completion Date
:
Sep 1, 2015
Actual Study Completion Date
:
Sep 1, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Immunosuppression Withdrawal Subjects may randomize to this group at 12 to 24 months after transplantation. This is followed by tapered withdrawal of calcineurin inhibitor-based immunosuppression therapy over the course of 1 year. |
Drug: calcineurin inhibitor-based immunosuppression
May be cyclosporine, mycophenolate mofetil, or tacrolimus
Procedure: liver transplant
Occurs at study entry
Other Names:
Drug: corticosteroids
3-month course of corticosteroids
Other Names:
Other: immunosuppression withdrawal
One year after transplantation, participants eligible for withdrawal are randomly assigned in a 4 to 1 ratio to immunosuppression withdrawal or to maintenance.
|
| Active Comparator: Immunosuppression Maintenance Liver transplant, followed by maintenance doses of continuous calcineurin inhibitor-based immunosuppression therapy. |
Drug: calcineurin inhibitor-based immunosuppression
May be cyclosporine, mycophenolate mofetil, or tacrolimus
Procedure: liver transplant
Occurs at study entry
Other Names:
Drug: corticosteroids
3-month course of corticosteroids
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Clinical Complications Usually Attributed to Immunosuppression [Randomization to 2 years post-randomization]
This is a composite endpoint comprising clinical complications related to immunosuppression and is defined as the occurrence of any of the following: death or graft loss, grade 4 secondary malignancy (graded by Common Terminology Criteria for Adverse Events [CTCAE] version 3.0), grade 4 opportunistic infection (graded by CTCAE version 3.0), stage 3 or higher fibrosis, or decrease in renal function. Decrease in renal function is defined as: a) the estimated glomerular filtration rate (eGFR) using creatinine obtained prior to and closest to randomization will be considered the baseline and will be compared to the eGFR using creatinine obtained at 24 months +/- 3 months after randomization; b) for those with a baseline eGFR 30-90 ml per min per 1.73 meter-squared, a 25% decrease in eGFR; c) for those with a baseline eGFR greater than 90 ml per min per 1.73 meter-squared, a 25% decrease in eGFR and a decrease in eGFR to less than 90 ml per min per 1.73 meter-squared.
Secondary Outcome Measures
- Number of Participants Who Qualify for Random Assignment [One to two years post-transplantation]
- Number of Participants Who Successfully Stop Taking Immunosuppression for at Least 6 Months [Randomization until study completion or participant termination (up to six years post-transplant)]
- Immunosuppression-free Duration [Discontinuation of all immunosuppression to end of trial participation or to time of restarting immunosuppression, whichever came first, assessed up to two years]
Time (in days) from withdrawing off of all immunosuppressive drugs to re-starting immunosuppression or study termination/completion.
- Number of Hepatitis C Infected Participants With Progression of Hepatitis C Related Liver Disease, Defined as Stage 4 or Higher Fibrosis on the Ishak Scale [Randomization to 2 years post-randomization.]
Number of subjects with a biopsy showing stage 4 fibrosis or higher on the Ishak scale. Stage 4 represents at least 13.7% fibrosis measurement with a description of fibrous expansion of portal areas with marked bridging (P-P) as well as portal to central (P-C). Stage 5 is marked bridging (P-P and/or P-C), with occasional nodules (incomplete cirrhosis) and stage 6 is cirrhosis, probable or definite.
- Number of Participants Experiencing Graft Loss or Death [Randomization to 2 years post-randomization.]
Number of participants with graft loss or death. Graft loss is defined as subject death or re-transplantation.
- Total Immunosuppression From Month 21 to Month 24 Post-randomization [Month 21 to Month 24 post-randomization]
Daily immunosuppression score in units per day averaged over the 3-month period from Month 21 to Month 24 post-randomization. Daily doses were assigned a score of 1 unit as follows: tacrolimus 1 mg, cyclosporine 100 mg, Sirolimus 1 mg, mycophenolate mofetil 1000 mg, Mycophenolic acid 720 mg, azathioprine 50 mg, and prednisone 5 mg. Any antibody use equaled 20 units. Unit scores based on Vasudev (Vasudev B, Hariharan S, Hussain SA, Zhu YR, Bresnahan BA et al. BK virus nephritis: risk factors, timing, and outcome in renal transplant recipients. Kidney Int. 2005; 8(4):1834-1839.)
- Total Burden of Immunosuppression From Random Assignment to Month 24 [Randomization to Month 24 post-randomization]
Total immunosuppression score in units taken as the sum of units per day over the 2-year period from randomization to Month 24 post-randomization. Daily doses were assigned a score of 1 unit as follows: tacrolimus 1 mg, cyclosporine 100 mg, Sirolimus 1 mg, mycophenolate mofetil 1000 mg, Mycophenolic acid 720 mg, azathioprine 50 mg, and prednisone 5 mg. Any antibody use equaled 20 units. Unit scores based on Vasudev (Vasudev B, Hariharan S, Hussain SA, Zhu YR, Bresnahan BA et al. BK virus nephritis: risk factors, timing, and outcome in renal transplant recipients. Kidney Int. 2005; 8(4):1834-1839.).
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Male or female 18 years of age or older.
-
Necessity for liver transplant.
-
For females of childbearing potential: a negative pregnancy test at study entry and agreement to use approved methods of birth control for the duration of their participation.
-
Ability to provide informed consent.
-
Availability of donor specimen(s).
-
For individuals with hepatitis C infection, presence of hepatitis genomes in blood.
Exclusion Criteria:
-
Previous transplant.
-
Multiorgan or split liver transplant other than with a right trisegment.
-
Living donor transplant.
-
Donor liver from a donor positive for antibody against hepatitis C.
-
Donor liver from a non-heart-beating donor.
-
Liver failure due to autoimmune disease.
-
Fulminant liver failure.
-
Hepatitis B infection as defined by the presence of HbSAg or hepatitis-C infection with a genome other than genome 1.
-
Stage III or higher hepatocellular cancer.
-
History of malignancy except hepatocellular cancer, adequately treated in situ cervical carcinoma,adequately treated basal or squamous cell carcinoma of skin, or other cancer judged to have a 5-year risk of recurrence less than 10%.
-
Active systemic infection at the time of transplantation.
-
Clinically significant chronic renal disease.
-
Clinically significant cardiovascular or cerebrovascular disease.
-
Infection with human immunodeficiency virus.
-
Any investigational drug received within 6 weeks of study entry or any investigational vaccine received at any time.
-
Hypersensitivity to tacrolimus.
-
Unwillingness or inability to comply with study requirements.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California, San Francisco | San Francisco | California | United States | 94143 |
| 2 | University of Colorado | Denver | Colorado | United States | 80262 |
| 3 | Northwestern University | Chicago | Illinois | United States | 60208 |
| 4 | University of Michigan | Ann Arbor | Michigan | United States | 48109 |
| 5 | Cleveland Clinic | Cleveland | Ohio | United States | 44195 |
| 6 | University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
| 7 | Baylor University | Dallas | Texas | United States | 76798 |
| 8 | University of Washington | Seattle | Washington | United States | 98195 |
Sponsors and Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Immune Tolerance Network (ITN)
Investigators
- Study Chair: Abraham Shaked, MD, PhD, University of Pennsylvania
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- National Institute of Allergy and Infectious Diseases website
- Click here for the Immune Tolerance Network website
Publications
None provided.Responsible Party:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00135694
Other Study ID Numbers:
- DAIT ITN030ST
First Posted:
Aug 26, 2005
Last Update Posted:
Feb 4, 2019
Last Verified:
Jan 1, 2019
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID)
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants with liver failure due to hepatitis C infection or non-immune, non-viral causes were enrolled between October 2005 and April 2011. |
|---|---|
| Pre-assignment Detail | Participants 12-24 months post-transplant, stable on immunosuppression monotherapy for at least 3 months prior to random assignment, with stage 2 or less fibrosis on the Ishak scale, adequate hepatic and renal function, and no biopsy-proven rejection were randomized between November 2006 and December 2012. |
| Arm/Group Title | Terminated Prior to Randomization | Randomized to Immunosuppression Withdrawal | Randomized to Immunosuppression Maintenance |
|---|---|---|---|
| Arm/Group Description | Subjects enrolled and transplanted into the trial but not eligible for randomization. | Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression withdrawal. | Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression maintenance. |
| Period Title: Overall Study | |||
| STARTED | 180 | 77 | 18 |
| COMPLETED | 0 | 56 | 11 |
| NOT COMPLETED | 180 | 21 | 7 |
Baseline Characteristics
| Arm/Group Title | Terminated Prior to Randomization | Randomized to Immunosuppression Withdrawal | Randomized to Immunosuppression Maintenance | Total |
|---|---|---|---|---|
| Arm/Group Description | Subjects enrolled and transplanted into the trial but not eligible for randomization. | Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression withdrawal. | Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression maintenance. | Total of all reporting groups |
| Overall Participants | 180 | 77 | 18 | 275 |
| Age (Count of Participants) | ||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
161
89.4%
|
68
88.3%
|
13
72.2%
|
242
88%
|
| >=65 years |
19
10.6%
|
9
11.7%
|
5
27.8%
|
33
12%
|
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
55.5
(7.83)
|
54.3
(9.92)
|
57.4
(7.70)
|
55.3
(8.47)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
53
29.4%
|
14
18.2%
|
5
27.8%
|
72
26.2%
|
| Male |
127
70.6%
|
63
81.8%
|
13
72.2%
|
203
73.8%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
10
5.6%
|
11
14.3%
|
3
16.7%
|
24
8.7%
|
| Not Hispanic or Latino |
167
92.8%
|
66
85.7%
|
15
83.3%
|
248
90.2%
|
| Unknown or Not Reported |
3
1.7%
|
0
0%
|
0
0%
|
3
1.1%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
1
0.6%
|
0
0%
|
0
0%
|
1
0.4%
|
| Asian |
2
1.1%
|
1
1.3%
|
1
5.6%
|
4
1.5%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
1
1.3%
|
0
0%
|
1
0.4%
|
| Black or African American |
22
12.2%
|
7
9.1%
|
0
0%
|
29
10.5%
|
| White |
153
85%
|
66
85.7%
|
17
94.4%
|
236
85.8%
|
| More than one race |
0
0%
|
1
1.3%
|
0
0%
|
1
0.4%
|
| Unknown or Not Reported |
2
1.1%
|
1
1.3%
|
0
0%
|
3
1.1%
|
| Region of Enrollment (participants) [Number] | ||||
| United States |
180
100%
|
77
100%
|
18
100%
|
275
100%
|
| Serum Creatinine (mg/dL) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [mg/dL] |
1.5
(1.18)
|
1.3
(0.65)
|
1.1
(0.68)
|
1.4
(1.04)
|
Outcome Measures
| Title | Number of Participants With Clinical Complications Usually Attributed to Immunosuppression |
|---|---|
| Description | This is a composite endpoint comprising clinical complications related to immunosuppression and is defined as the occurrence of any of the following: death or graft loss, grade 4 secondary malignancy (graded by Common Terminology Criteria for Adverse Events [CTCAE] version 3.0), grade 4 opportunistic infection (graded by CTCAE version 3.0), stage 3 or higher fibrosis, or decrease in renal function. Decrease in renal function is defined as: a) the estimated glomerular filtration rate (eGFR) using creatinine obtained prior to and closest to randomization will be considered the baseline and will be compared to the eGFR using creatinine obtained at 24 months +/- 3 months after randomization; b) for those with a baseline eGFR 30-90 ml per min per 1.73 meter-squared, a 25% decrease in eGFR; c) for those with a baseline eGFR greater than 90 ml per min per 1.73 meter-squared, a 25% decrease in eGFR and a decrease in eGFR to less than 90 ml per min per 1.73 meter-squared. |
| Time Frame | Randomization to 2 years post-randomization |
Outcome Measure Data
| Analysis Population Description |
|---|
| Evaluable randomized subjects having a targeted event and/or having available data for calculation of eGFR |
| Arm/Group Title | Randomized to Immunosuppression Withdrawal | Randomized to Immunosuppression Maintenance |
|---|---|---|
| Arm/Group Description | Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression withdrawal. | Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression maintenance. |
| Measure Participants | 66 | 13 |
| Number [participants] |
12
6.7%
|
4
5.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Randomized to Immunosuppression Withdrawal, Randomized to Immunosuppression Maintenance |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference (RD) |
| Estimated Value | -13 | |
| Confidence Interval |
(2-Sided) 90% -35 to 10 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants Who Qualify for Random Assignment |
|---|---|
| Description | |
| Time Frame | One to two years post-transplantation |
Outcome Measure Data
| Analysis Population Description |
|---|
| All subjects transplanted |
| Arm/Group Title | All Enrolled |
|---|---|
| Arm/Group Description | Subjects who underwent liver transplantation in the trial. |
| Measure Participants | 275 |
| Number [participants] |
95
52.8%
|
| Title | Number of Participants Who Successfully Stop Taking Immunosuppression for at Least 6 Months |
|---|---|
| Description | |
| Time Frame | Randomization until study completion or participant termination (up to six years post-transplant) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants randomized to immunosuppression withdrawal |
| Arm/Group Title | Randomized to Immunosuppression Withdrawal |
|---|---|
| Arm/Group Description | Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression withdrawal. |
| Measure Participants | 77 |
| Number [participants] |
12
6.7%
|
| Title | Immunosuppression-free Duration |
|---|---|
| Description | Time (in days) from withdrawing off of all immunosuppressive drugs to re-starting immunosuppression or study termination/completion. |
| Time Frame | Discontinuation of all immunosuppression to end of trial participation or to time of restarting immunosuppression, whichever came first, assessed up to two years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants randomized to immunosuppression withdrawal who completed withdrawal and discontinued all immunosuppression |
| Arm/Group Title | Randomized to Immunosuppression Withdrawal |
|---|---|
| Arm/Group Description | Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression withdrawal. |
| Measure Participants | 14 |
| Mean (Full Range) [Days] |
555.2
|
| Title | Number of Hepatitis C Infected Participants With Progression of Hepatitis C Related Liver Disease, Defined as Stage 4 or Higher Fibrosis on the Ishak Scale |
|---|---|
| Description | Number of subjects with a biopsy showing stage 4 fibrosis or higher on the Ishak scale. Stage 4 represents at least 13.7% fibrosis measurement with a description of fibrous expansion of portal areas with marked bridging (P-P) as well as portal to central (P-C). Stage 5 is marked bridging (P-P and/or P-C), with occasional nodules (incomplete cirrhosis) and stage 6 is cirrhosis, probable or definite. |
| Time Frame | Randomization to 2 years post-randomization. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Hepatitis C infected participants randomized. |
| Arm/Group Title | Randomized to Immunosuppression Withdrawal | Randomized to Immunosuppression Maintenance |
|---|---|---|
| Arm/Group Description | Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression withdrawal. | Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression maintenance. |
| Measure Participants | 30 | 7 |
| Number [participants] |
0
0%
|
0
0%
|
| Title | Number of Participants Experiencing Graft Loss or Death |
|---|---|
| Description | Number of participants with graft loss or death. Graft loss is defined as subject death or re-transplantation. |
| Time Frame | Randomization to 2 years post-randomization. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants (intent-to-treat sample) |
| Arm/Group Title | Randomized to Immunosuppression Withdrawal | Randomized to Immunosuppression Maintenance |
|---|---|---|
| Arm/Group Description | Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression withdrawal. | Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression maintenance. |
| Measure Participants | 77 | 18 |
| Number [participants] |
1
0.6%
|
0
0%
|
| Title | Total Immunosuppression From Month 21 to Month 24 Post-randomization |
|---|---|
| Description | Daily immunosuppression score in units per day averaged over the 3-month period from Month 21 to Month 24 post-randomization. Daily doses were assigned a score of 1 unit as follows: tacrolimus 1 mg, cyclosporine 100 mg, Sirolimus 1 mg, mycophenolate mofetil 1000 mg, Mycophenolic acid 720 mg, azathioprine 50 mg, and prednisone 5 mg. Any antibody use equaled 20 units. Unit scores based on Vasudev (Vasudev B, Hariharan S, Hussain SA, Zhu YR, Bresnahan BA et al. BK virus nephritis: risk factors, timing, and outcome in renal transplant recipients. Kidney Int. 2005; 8(4):1834-1839.) |
| Time Frame | Month 21 to Month 24 post-randomization |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants still being followed 24 months post-randomization. |
| Arm/Group Title | Randomized to Immunosuppression Withdrawal | Randomized to Immunosuppression Maintenance |
|---|---|---|
| Arm/Group Description | Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression withdrawal. | Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression maintenance. |
| Measure Participants | 64 | 13 |
| Mean (Full Range) [units per day] |
2.8
|
3.7
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Randomized to Immunosuppression Withdrawal, Randomized to Immunosuppression Maintenance |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0183 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Adjusted for immunosuppression dose the subject was receiving at the time of randomization. | |
| Title | Total Burden of Immunosuppression From Random Assignment to Month 24 |
|---|---|
| Description | Total immunosuppression score in units taken as the sum of units per day over the 2-year period from randomization to Month 24 post-randomization. Daily doses were assigned a score of 1 unit as follows: tacrolimus 1 mg, cyclosporine 100 mg, Sirolimus 1 mg, mycophenolate mofetil 1000 mg, Mycophenolic acid 720 mg, azathioprine 50 mg, and prednisone 5 mg. Any antibody use equaled 20 units. Unit scores based on Vasudev (Vasudev B, Hariharan S, Hussain SA, Zhu YR, Bresnahan BA et al. BK virus nephritis: risk factors, timing, and outcome in renal transplant recipients. Kidney Int. 2005; 8(4):1834-1839.). |
| Time Frame | Randomization to Month 24 post-randomization |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants still being followed 24 months post-randomization. |
| Arm/Group Title | Randomized to Immunosuppression Withdrawal | Randomized to Immunosuppression Maintenance |
|---|---|---|
| Arm/Group Description | Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression withdrawal. | Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression maintenance. |
| Measure Participants | 64 | 13 |
| Mean (Full Range) [units] |
2198.5
|
2708.4
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Randomized to Immunosuppression Withdrawal, Randomized to Immunosuppression Maintenance |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Adjusted for immunosuppression dose the subject was receiving at the time of randomization. | |
Adverse Events
| Time Frame | Enrollment through end of study (up to 7 years) | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Terminated Prior to Randomization | Randomized to Immunosuppression Withdrawal | Randomized to Immunosuppression Maintenance | |||
| Arm/Group Description | Subjects enrolled and transplanted into the trial but not eligible for randomization. | Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression withdrawal. | Subjects enrolled and transplanted into the trial and followed for at least one year and eligible for random assignment and randomized to immunosuppression maintenance. | |||
All Cause Mortality |
||||||
| Terminated Prior to Randomization | Randomized to Immunosuppression Withdrawal | Randomized to Immunosuppression Maintenance | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Terminated Prior to Randomization | Randomized to Immunosuppression Withdrawal | Randomized to Immunosuppression Maintenance | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 89/180 (49.4%) | 9/18 (50%) | 54/77 (70.1%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 7/180 (3.9%) | 7 | 0/18 (0%) | 0 | 2/77 (2.6%) | 2 |
| Coagulopathy | 1/180 (0.6%) | 2 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Leukocytosis | 2/180 (1.1%) | 2 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Neutropenia | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Pancytopenia | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Thrombocytopenia | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Cardiac disorders | ||||||
| Angina pectoris | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Angina unstable | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Atrial fibrillation | 3/180 (1.7%) | 3 | 2/18 (11.1%) | 2 | 0/77 (0%) | 0 |
| Atrioventricular block complete | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Cardiac arrest | 2/180 (1.1%) | 2 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Cardiac failure | 2/180 (1.1%) | 2 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Cardiac failure acute | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Cardiac failure congestive | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Cardio-respiratory arrest | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Coronary artery disease | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Myocardial infarction | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Pericardial effusion | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Supraventricular extrasystoles | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Supraventricular tachycardia | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 2/77 (2.6%) | 2 |
| Ventricular tachycardia | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Endocrine disorders | ||||||
| Hypothyroidism | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Abdominal distension | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Abdominal hernia | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 2/77 (2.6%) | 2 |
| Abdominal pain | 3/180 (1.7%) | 3 | 0/18 (0%) | 0 | 2/77 (2.6%) | 3 |
| Abdominal pain upper | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Ascites | 4/180 (2.2%) | 6 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Diarrhoea | 2/180 (1.1%) | 3 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Femoral hernia, obstructive | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Food poisoning | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Gastrointestinal haemorrhage | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Gastrooesophageal reflux disease | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Ileus | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Inguinal hernia | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 2/77 (2.6%) | 2 |
| Inguinal hernia, obstructive | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Intestinal strangulation | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Intra-abdominal haemorrhage | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Large intestine perforation | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Nausea | 3/180 (1.7%) | 5 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Oesophageal varices haemorrhage | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Pancreatitis necrotising | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Peritoneal effusion | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Rectal haemorrhage | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Retroperitoneal haemorrhage | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Small intestinal obstruction | 2/180 (1.1%) | 2 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Umbilical hernia | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Vomiting | 3/180 (1.7%) | 3 | 0/18 (0%) | 0 | 2/77 (2.6%) | 2 |
| General disorders | ||||||
| Chest pain | 2/180 (1.1%) | 2 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Death | 2/180 (1.1%) | 2 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Fatigue | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Hernia obstructive | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Oedema peripheral | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Pyrexia | 5/180 (2.8%) | 6 | 0/18 (0%) | 0 | 4/77 (5.2%) | 4 |
| Hepatobiliary disorders | ||||||
| Bile duct obstruction | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 1/77 (1.3%) | 1 |
| Bile duct stenosis | 0/180 (0%) | 0 | 2/18 (11.1%) | 2 | 4/77 (5.2%) | 4 |
| Cholangitis | 4/180 (2.2%) | 5 | 2/18 (11.1%) | 2 | 0/77 (0%) | 0 |
| Cholelithiasis | 1/180 (0.6%) | 2 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Cholestasis | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Chronic hepatic failure | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Hepatic artery stenosis | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Hepatic cirrhosis | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Hepatic steatosis | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Hepatitis cholestatic | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Hepatorenal syndrome | 2/180 (1.1%) | 2 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Immune system disorders | ||||||
| Graft versus host disease | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Transplant rejection | 26/180 (14.4%) | 28 | 1/18 (5.6%) | 1 | 21/77 (27.3%) | 25 |
| Infections and infestations | ||||||
| Abdominal abscess | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Aspergillosis | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Bacteraemia | 2/180 (1.1%) | 2 | 0/18 (0%) | 0 | 2/77 (2.6%) | 2 |
| Beta haemolytic streptococcal infection | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Brain abscess | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Bronchopulmonary aspergillosis | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Catheter related infection | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Cellulitis | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 4/77 (5.2%) | 4 |
| Clostridial infection | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Clostridium difficile colitis | 2/180 (1.1%) | 2 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Coxsackie viral infection | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Cryptococcosis | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Cytomegalovirus colitis | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Cytomegalovirus infection | 3/180 (1.7%) | 3 | 0/18 (0%) | 0 | 2/77 (2.6%) | 2 |
| Diverticulitis | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Empyema | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Enterococcal bacteraemia | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Escherichia bacteraemia | 1/180 (0.6%) | 1 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Gastroenteritis | 2/180 (1.1%) | 2 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Groin abscess | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Hepatitis C | 7/180 (3.9%) | 7 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Herpes simplex | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Liver abscess | 2/180 (1.1%) | 2 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Meningitis cryptococcal | 1/180 (0.6%) | 2 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Perihepatic abscess | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Peritonitis bacterial | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Pneumonia | 1/180 (0.6%) | 2 | 1/18 (5.6%) | 1 | 1/77 (1.3%) | 1 |
| Pneumonia staphylococcal | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Postoperative wound infection | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Sepsis | 8/180 (4.4%) | 8 | 2/18 (11.1%) | 2 | 2/77 (2.6%) | 2 |
| Streptococcal bacteraemia | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Urinary tract infection | 3/180 (1.7%) | 3 | 0/18 (0%) | 0 | 3/77 (3.9%) | 3 |
| Viral diarrhoea | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Viral infection | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Wound infection | 4/180 (2.2%) | 4 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Biliary anastomosis complication | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Fall | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Graft dysfunction | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Hip fracture | 1/180 (0.6%) | 2 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Incisional hernia | 2/180 (1.1%) | 2 | 1/18 (5.6%) | 1 | 6/77 (7.8%) | 6 |
| Injury | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Joint dislocation | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Medical device complication | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 2 |
| Poisoning | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Post procedural bile leak | 7/180 (3.9%) | 7 | 1/18 (5.6%) | 1 | 1/77 (1.3%) | 1 |
| Post procedural haemorrhage | 2/180 (1.1%) | 2 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Procedural complication | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Therapeutic agent toxicity | 2/180 (1.1%) | 2 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Vascular pseudoaneurysm | 2/180 (1.1%) | 2 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Wound dehiscence | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Wound secretion | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Investigations | ||||||
| Alanine aminotransferase increased | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Aspartate aminotransferase increased | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Blood alkaline phosphatase increased | 1/180 (0.6%) | 2 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Blood bilirubin increased | 2/180 (1.1%) | 2 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Blood creatinine increased | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 2/77 (2.6%) | 2 |
| Electrocardiogram T wave inversion | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Gamma-glutamyltransferase increased | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Hepatic enzyme increased | 4/180 (2.2%) | 4 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Liver function test abnormal | 4/180 (2.2%) | 4 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Transaminases increased | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||
| Dehydration | 5/180 (2.8%) | 6 | 0/18 (0%) | 0 | 5/77 (6.5%) | 5 |
| Diabetes mellitus | 2/180 (1.1%) | 2 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Fluid overload | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Hyperglycaemia | 3/180 (1.7%) | 3 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Hyperkalaemia | 9/180 (5%) | 11 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Hypoglycaemia | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Hypoglycaemic seizure | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Hypomagnesaemia | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 2/77 (2.6%) | 2 |
| Hyponatraemia | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Obesity | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 1/77 (1.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Groin pain | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Muscular weakness | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Osteoarthritis | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 2/77 (2.6%) | 2 |
| Polyarthritis | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Hepatic neoplasm malignant | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Hepatic neoplasm malignant recurrent | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Multiple myeloma | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Myelodysplastic syndrome | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Squamous cell carcinoma | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Nervous system disorders | ||||||
| Central pontine myelinolysis | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Cerebral haemorrhage | 3/180 (1.7%) | 4 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Cerebral infarction | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 2/77 (2.6%) | 2 |
| Cerebrovascular accident | 2/180 (1.1%) | 2 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Convulsion | 5/180 (2.8%) | 5 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Haemorrhagic stroke | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Hepatic encephalopathy | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 2/77 (2.6%) | 2 |
| Lacunar infarction | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Reversible posterior leukoencephalopathy syndrome | 1/180 (0.6%) | 2 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Subarachnoid haemorrhage | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Psychiatric disorders | ||||||
| Confusional state | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Mental disorder due to a general medical condition | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Mental status changes | 4/180 (2.2%) | 4 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Suicide attempt | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Renal and urinary disorders | ||||||
| Anuria | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Calculus ureteric | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Haematuria | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 1/77 (1.3%) | 1 |
| Renal failure | 4/180 (2.2%) | 4 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Renal failure acute | 5/180 (2.8%) | 5 | 0/18 (0%) | 0 | 3/77 (3.9%) | 5 |
| Renal failure chronic | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Tubulointerstitial nephritis | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Asthma | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Dyspnoea | 4/180 (2.2%) | 4 | 0/18 (0%) | 0 | 3/77 (3.9%) | 3 |
| Epistaxis | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Haemothorax | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Hypoxia | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Lung disorder | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Pleural effusion | 4/180 (2.2%) | 5 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Pneumonia aspiration | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Pulmonary cavitation | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Pulmonary embolism | 2/180 (1.1%) | 2 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Respiratory failure | 4/180 (2.2%) | 4 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Pruritus | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Rash | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Social circumstances | ||||||
| Treatment noncompliance | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Surgical and medical procedures | ||||||
| Gastrectomy | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 1/77 (1.3%) | 1 |
| Haematoma evacuation | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Inguinal hernia repair | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Medical device change | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Small intestinal resection | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Spinal fusion surgery | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Vascular disorders | ||||||
| Deep vein thrombosis | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Haemorrhage | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Hypertension | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
| Hypotension | 3/180 (1.7%) | 3 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Venous thrombosis | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 0/77 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| Terminated Prior to Randomization | Randomized to Immunosuppression Withdrawal | Randomized to Immunosuppression Maintenance | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 155/180 (86.1%) | 18/18 (100%) | 76/77 (98.7%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 27/180 (15%) | 37 | 3/18 (16.7%) | 3 | 11/77 (14.3%) | 14 |
| Neutropenia | 7/180 (3.9%) | 7 | 2/18 (11.1%) | 2 | 4/77 (5.2%) | 4 |
| Thrombocytopenia | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 2/77 (2.6%) | 2 |
| Cardiac disorders | ||||||
| Bradycardia | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Ear and labyrinth disorders | ||||||
| Ear pain | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Eye disorders | ||||||
| Ocular icterus | 6/180 (3.3%) | 6 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Visual impairment | 2/180 (1.1%) | 2 | 1/18 (5.6%) | 1 | 1/77 (1.3%) | 1 |
| Gastrointestinal disorders | ||||||
| Abdominal distension | 7/180 (3.9%) | 7 | 1/18 (5.6%) | 1 | 3/77 (3.9%) | 3 |
| Abdominal hernia | 2/180 (1.1%) | 2 | 3/18 (16.7%) | 3 | 1/77 (1.3%) | 1 |
| Abdominal pain | 9/180 (5%) | 11 | 0/18 (0%) | 0 | 7/77 (9.1%) | 7 |
| Abdominal pain upper | 3/180 (1.7%) | 3 | 1/18 (5.6%) | 1 | 4/77 (5.2%) | 4 |
| Ascites | 13/180 (7.2%) | 15 | 1/18 (5.6%) | 1 | 2/77 (2.6%) | 2 |
| Constipation | 6/180 (3.3%) | 7 | 0/18 (0%) | 0 | 6/77 (7.8%) | 8 |
| Diarrhoea | 25/180 (13.9%) | 28 | 2/18 (11.1%) | 2 | 13/77 (16.9%) | 18 |
| Dyspepsia | 1/180 (0.6%) | 1 | 1/18 (5.6%) | 1 | 1/77 (1.3%) | 1 |
| Gastrooesophageal reflux disease | 1/180 (0.6%) | 1 | 1/18 (5.6%) | 1 | 4/77 (5.2%) | 5 |
| Nausea | 11/180 (6.1%) | 12 | 2/18 (11.1%) | 2 | 10/77 (13%) | 13 |
| Umbilical hernia | 3/180 (1.7%) | 3 | 0/18 (0%) | 0 | 4/77 (5.2%) | 4 |
| Vomiting | 6/180 (3.3%) | 6 | 0/18 (0%) | 0 | 9/77 (11.7%) | 11 |
| General disorders | ||||||
| Asthenia | 4/180 (2.2%) | 4 | 1/18 (5.6%) | 1 | 2/77 (2.6%) | 2 |
| Fatigue | 8/180 (4.4%) | 9 | 0/18 (0%) | 0 | 8/77 (10.4%) | 9 |
| Influenza like illness | 2/180 (1.1%) | 2 | 0/18 (0%) | 0 | 5/77 (6.5%) | 7 |
| Oedema | 12/180 (6.7%) | 14 | 0/18 (0%) | 0 | 5/77 (6.5%) | 5 |
| Oedema peripheral | 43/180 (23.9%) | 45 | 4/18 (22.2%) | 4 | 16/77 (20.8%) | 18 |
| Pyrexia | 15/180 (8.3%) | 17 | 1/18 (5.6%) | 1 | 13/77 (16.9%) | 17 |
| Hepatobiliary disorders | ||||||
| Bile duct stenosis | 8/180 (4.4%) | 8 | 0/18 (0%) | 0 | 6/77 (7.8%) | 6 |
| Biloma | 2/180 (1.1%) | 2 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Cholestasis | 1/180 (0.6%) | 1 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Immune system disorders | ||||||
| Hypersensitivity | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Transplant rejection | 18/180 (10%) | 18 | 2/18 (11.1%) | 2 | 15/77 (19.5%) | 15 |
| Infections and infestations | ||||||
| Bronchitis | 1/180 (0.6%) | 1 | 1/18 (5.6%) | 1 | 5/77 (6.5%) | 5 |
| Cellulitis | 3/180 (1.7%) | 3 | 0/18 (0%) | 0 | 7/77 (9.1%) | 7 |
| Escherichia bacteraemia | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Gastroenteritis viral | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 4/77 (5.2%) | 6 |
| Hepatitis C | 35/180 (19.4%) | 35 | 2/18 (11.1%) | 2 | 16/77 (20.8%) | 16 |
| Herpes zoster | 1/180 (0.6%) | 1 | 1/18 (5.6%) | 1 | 4/77 (5.2%) | 4 |
| Nasopharyngitis | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 4/77 (5.2%) | 5 |
| Pneumonia | 6/180 (3.3%) | 6 | 0/18 (0%) | 0 | 5/77 (6.5%) | 5 |
| Sinusitis | 3/180 (1.7%) | 3 | 0/18 (0%) | 0 | 7/77 (9.1%) | 8 |
| Upper respiratory tract infection | 3/180 (1.7%) | 3 | 0/18 (0%) | 0 | 8/77 (10.4%) | 11 |
| Urinary tract infection | 14/180 (7.8%) | 16 | 0/18 (0%) | 0 | 10/77 (13%) | 22 |
| Injury, poisoning and procedural complications | ||||||
| Biliary anastomosis complication | 2/180 (1.1%) | 2 | 0/18 (0%) | 0 | 4/77 (5.2%) | 4 |
| Concussion | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Foot fracture | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 2/77 (2.6%) | 2 |
| Incision site complication | 8/180 (4.4%) | 8 | 1/18 (5.6%) | 1 | 6/77 (7.8%) | 6 |
| Incision site pain | 5/180 (2.8%) | 5 | 1/18 (5.6%) | 1 | 6/77 (7.8%) | 7 |
| Incisional hernia | 6/180 (3.3%) | 6 | 3/18 (16.7%) | 3 | 2/77 (2.6%) | 2 |
| Post procedural bile leak | 14/180 (7.8%) | 15 | 2/18 (11.1%) | 2 | 2/77 (2.6%) | 2 |
| Rib fracture | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Upper limb fracture | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 1/77 (1.3%) | 1 |
| Investigations | ||||||
| Alanine aminotransferase increased | 3/180 (1.7%) | 3 | 1/18 (5.6%) | 1 | 6/77 (7.8%) | 10 |
| Aspartate aminotransferase increased | 2/180 (1.1%) | 2 | 1/18 (5.6%) | 1 | 5/77 (6.5%) | 9 |
| Blood alkaline phosphatase increased | 3/180 (1.7%) | 4 | 1/18 (5.6%) | 1 | 6/77 (7.8%) | 7 |
| Blood bilirubin increased | 3/180 (1.7%) | 3 | 1/18 (5.6%) | 1 | 3/77 (3.9%) | 5 |
| Blood creatinine increased | 8/180 (4.4%) | 8 | 1/18 (5.6%) | 1 | 8/77 (10.4%) | 8 |
| Blood glucose increased | 4/180 (2.2%) | 4 | 1/18 (5.6%) | 1 | 4/77 (5.2%) | 4 |
| Breath sounds abnormal | 11/180 (6.1%) | 12 | 3/18 (16.7%) | 3 | 11/77 (14.3%) | 12 |
| Eosinophil count increased | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Gamma-glutamyltransferase increased | 3/180 (1.7%) | 3 | 1/18 (5.6%) | 1 | 5/77 (6.5%) | 7 |
| Haematocrit decreased | 2/180 (1.1%) | 2 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Haemoglobin decreased | 3/180 (1.7%) | 3 | 1/18 (5.6%) | 1 | 1/77 (1.3%) | 1 |
| Hepatic enzyme increased | 7/180 (3.9%) | 7 | 0/18 (0%) | 0 | 9/77 (11.7%) | 9 |
| International normalised ratio increased | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 3/77 (3.9%) | 3 |
| Liver function test abnormal | 14/180 (7.8%) | 14 | 3/18 (16.7%) | 4 | 25/77 (32.5%) | 32 |
| Lymphocyte count decreased | 1/180 (0.6%) | 1 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Red blood cell count decreased | 1/180 (0.6%) | 1 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Weight increased | 1/180 (0.6%) | 1 | 1/18 (5.6%) | 1 | 5/77 (6.5%) | 5 |
| Metabolism and nutrition disorders | ||||||
| Dehydration | 3/180 (1.7%) | 3 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Diabetes mellitus | 29/180 (16.1%) | 29 | 2/18 (11.1%) | 3 | 20/77 (26%) | 20 |
| Gout | 1/180 (0.6%) | 2 | 1/18 (5.6%) | 1 | 3/77 (3.9%) | 4 |
| Hyperglycaemia | 19/180 (10.6%) | 19 | 0/18 (0%) | 0 | 15/77 (19.5%) | 17 |
| Hyperkalaemia | 28/180 (15.6%) | 35 | 3/18 (16.7%) | 3 | 23/77 (29.9%) | 28 |
| Hyperphosphataemia | 2/180 (1.1%) | 3 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Hypoglycaemia | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Hypomagnesaemia | 14/180 (7.8%) | 14 | 2/18 (11.1%) | 2 | 13/77 (16.9%) | 14 |
| Metabolic syndrome | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 5/180 (2.8%) | 5 | 1/18 (5.6%) | 1 | 7/77 (9.1%) | 7 |
| Back pain | 4/180 (2.2%) | 4 | 1/18 (5.6%) | 1 | 10/77 (13%) | 10 |
| Muscle spasms | 5/180 (2.8%) | 5 | 0/18 (0%) | 0 | 4/77 (5.2%) | 5 |
| Musculoskeletal pain | 3/180 (1.7%) | 4 | 0/18 (0%) | 0 | 4/77 (5.2%) | 4 |
| Neck pain | 3/180 (1.7%) | 3 | 0/18 (0%) | 0 | 7/77 (9.1%) | 7 |
| Pain in extremity | 1/180 (0.6%) | 1 | 1/18 (5.6%) | 1 | 1/77 (1.3%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Basal cell carcinoma | 0/180 (0%) | 0 | 0/18 (0%) | 0 | 4/77 (5.2%) | 4 |
| Lung neoplasm | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Melanocytic naevus | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 1/77 (1.3%) | 1 |
| Nervous system disorders | ||||||
| Convulsion | 2/180 (1.1%) | 2 | 1/18 (5.6%) | 1 | 1/77 (1.3%) | 1 |
| Dizziness | 4/180 (2.2%) | 5 | 1/18 (5.6%) | 1 | 2/77 (2.6%) | 2 |
| Encephalopathy | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Headache | 13/180 (7.2%) | 13 | 0/18 (0%) | 0 | 11/77 (14.3%) | 15 |
| Hypoaesthesia | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 2/77 (2.6%) | 2 |
| Neuropathy peripheral | 3/180 (1.7%) | 3 | 1/18 (5.6%) | 1 | 5/77 (6.5%) | 5 |
| Tremor | 11/180 (6.1%) | 12 | 2/18 (11.1%) | 2 | 9/77 (11.7%) | 13 |
| Psychiatric disorders | ||||||
| Confusional state | 10/180 (5.6%) | 10 | 0/18 (0%) | 0 | 1/77 (1.3%) | 1 |
| Depression | 6/180 (3.3%) | 6 | 3/18 (16.7%) | 5 | 5/77 (6.5%) | 5 |
| Insomnia | 6/180 (3.3%) | 6 | 0/18 (0%) | 0 | 6/77 (7.8%) | 7 |
| Renal and urinary disorders | ||||||
| Renal failure | 27/180 (15%) | 27 | 3/18 (16.7%) | 3 | 15/77 (19.5%) | 16 |
| Renal failure acute | 12/180 (6.7%) | 13 | 0/18 (0%) | 0 | 4/77 (5.2%) | 4 |
| Renal tubular necrosis | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Reproductive system and breast disorders | ||||||
| Erectile dysfunction | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 1/77 (1.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 4/77 (5.2%) | 4 |
| Dyspnoea | 6/180 (3.3%) | 7 | 0/18 (0%) | 0 | 6/77 (7.8%) | 6 |
| Pleural effusion | 15/180 (8.3%) | 16 | 1/18 (5.6%) | 1 | 6/77 (7.8%) | 6 |
| Pneumothorax | 2/180 (1.1%) | 2 | 1/18 (5.6%) | 1 | 2/77 (2.6%) | 2 |
| Productive cough | 1/180 (0.6%) | 1 | 0/18 (0%) | 0 | 4/77 (5.2%) | 4 |
| Upper respiratory tract congestion | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Cold sweat | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Erythema | 0/180 (0%) | 0 | 1/18 (5.6%) | 2 | 0/77 (0%) | 0 |
| Precancerous skin lesion | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Pruritus | 7/180 (3.9%) | 8 | 1/18 (5.6%) | 1 | 5/77 (6.5%) | 6 |
| Rash | 5/180 (2.8%) | 5 | 1/18 (5.6%) | 2 | 4/77 (5.2%) | 5 |
| Skin ulcer | 1/180 (0.6%) | 1 | 1/18 (5.6%) | 1 | 1/77 (1.3%) | 1 |
| Surgical and medical procedures | ||||||
| Finger amputation | 0/180 (0%) | 0 | 1/18 (5.6%) | 1 | 0/77 (0%) | 0 |
| Vascular disorders | ||||||
| Hypertension | 12/180 (6.7%) | 12 | 2/18 (11.1%) | 2 | 9/77 (11.7%) | 9 |
| Hypotension | 5/180 (2.8%) | 5 | 1/18 (5.6%) | 1 | 2/77 (2.6%) | 2 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Director, Clinical Research Operations Program |
|---|---|
| Organization | DAIT/NIAID |
| Phone | 301-594-7669 |
| DAITClinicalTrialsGov@niaid.nih.gov |
Responsible Party:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00135694
Other Study ID Numbers:
- DAIT ITN030ST
First Posted:
Aug 26, 2005
Last Update Posted:
Feb 4, 2019
Last Verified:
Jan 1, 2019