Liver Transplant, Liver Transplantation
Conditions
Keywords
immunosuppression withdrawal (IS), anti-rejection drugs, tolerance, allograft function
Brief summary
Antirejection medicines, also known as immunosuppressive drugs, are prescribed to organ transplant recipients to prevent their bodies from rejecting the new organ. Long-term use of these drugs places transplant recipients at higher risk of serious infections and certain types of cancer. The purpose of this study is to determine whether immunosuppressive drugs can be safely withdrawn over a minimum of 9 months from children who received liver transplants at least 4 years ago.
Detailed description
In order to prevent the rejection of transplanted organs, transplant recipients are prescribed a strict, lifelong regimen of immunosuppressive drugs. While these drugs help prevent the body from rejecting the transplant, they carry numerous complications, including increased risk of serious infections and certain types of cancer. However, there is mounting evidence that a significant percentage of liver transplant recipients can maintain a healthy, functioning transplant without ongoing immunosuppression. This study will determine whether gradual withdrawal and eventual discontinuation of all immunosuppressive medication can be safely accomplished in children who received a liver transplant from a parent. Twenty eligible participants who were under 18 years old at the time of transplant, whose donor was a parent, and who received the transplant at least four years ago will be enrolled in the study. Liver recipients will have an initial screening assessment consisting of a medical history, liver biopsy, and urine and blood collection. Eligible recipients will be placed on a modified medication schedule to gradually decrease their immunosuppression medication slowly over a 9- to 12-month period, during which time they will be closely monitored by study staff. Immunosuppressive drugs will not be provided by this study. For a minimum of 3 and up to a maximum of 7 years, monthly telephone consultations and quarterly study visits will occur. Visits will include physical exams and blood collection to monitor the children's health during the withdrawal phase. The exact schedule of immunosuppressant withdrawal will be determined by study physicians based on participant's health and immune function test results. Donor and nondonor parents will be asked to each provide one blood sample during the initial study visits for immunologic and genetic testing. \*\*\* IMPORTANT NOTICE: \*\*\* The National Institute of Allergy and Infectious Diseases and the Immune Tolerance Network do not recommend the discontinuation of immunosuppressive therapy for recipients of cell, organ, or tissue transplants outside of physician-directed, controlled clinical studies. Discontinuation of prescribed immunosuppressive therapy can result in serious health consequences and should only be performed in certain rare circumstances, upon the recommendation and with the guidance of your health care provider.
Interventions
Gradual withdrawal of immunosuppressive medication. With high dose, daily dose reduction by 25% for 8 weeks. With low dose, daily dose reduction by 25% for 4 weeks.
Sponsors
Immune Tolerance Network (ITN)
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Recipients of parental living-donor liver allografts will undergo gradual withdrawal as tolerated of immunosuppression with the goal of complete withdrawal.
Eligibility
Sex/Gender
ALL
Age
4 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
for Liver Recipients: * Received liver from living parent donor * Received transplant at least 4 years prior to study entry * Less than 18 years of age at time of transplant * Parent or guardian willing to provide informed consent Inclusion Criteria for Liver Donors: * Willing to participate in this study
Exclusion criteria
for Liver Recipients: * Underwent transplant because of liver failure related to autoimmune disease * Underwent transplant of a second organ simultaneously with or after liver transplant OR liver retransplantation * Receiving immunosuppression with more than one drug * 50% increase in dose of current immunosuppressive drug * HIV infection * Hepatitis B or C virus infection * Pregnancy or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Successfully Withdrawn From Immunosuppression | 1 year after completion of immunosuppression withdrawal | Participants were considered successfully withdrawn from immunosuppression if they remained off immunosuppression for at least one year with normal allograft function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time From Start of Immunosuppression Withdrawal to the First Episode of Acute Rejection, Second Episode of Rejection That Did Not Require Treatment, or to Diagnosis of Chronic Rejection | From the start of immunosuppression withdrawal to first acute rejection, second episode of rejection that did not require treatment, or diagnosis of chronic rejection through end of study (up to 9.5 years) | The number of days between the start of immunosuppression (IS) withdrawal and the first episode of acute rejection (either clinical rejection or based on BANFF criteria), second episode of rejection that did not require treatment, or the first diagnosis of chronic rejection. |
| Immunosuppression-Free Duration | Completion of Withdrawal to either end of trial participation (up to 9.5 years) or time to restarting immunosuppression | The number of months between the end of immunosuppression withdrawal and either the end of trial participation or the time of restarting immunosuppression |
| Distribution of Histologic Severity Among Rejection Episodes | Start of immunosuppressive withdrawal to rejection through end of study (up to 9.5 years) | The number of participants within each level of histologic severity based on BANFF grading criteria (Mild, Moderate, Severe). |
| Number of Participants Experiencing Adverse Events by Severity | Enrollment through end of study (up to 9.5 years) | The results provide the total number of participants experiencing adverse events (AEs). Participants experiencing AEs are stratified into five severity categories: mild, moderate, severe, life-threatening, and death, based on National Cancer Institute--Common Terminology Criteria (NCI-CTCAE) Version 3.0. |
| Number of Participants Who Suffered Graft Loss or Died Following Initiation of Immunosuppression Withdrawal | Enrollment through end of study (up to 9.5 years) | Participants who died while on the study for any reason as well as participants that experienced the loss of their transplant while a participant in the study. |
| Percent Change From Baseline in Total Cholesterol | Enrollment through end of study (up to 9.5 years) | Percent change from baseline in total serum cholesterol. Cholesterol is a waxy substance your body needs to build cells, but too much can be a problem since it can build-up in arteries. Narrowed arteries can result in heart attack or stroke. This outcome looks at the percent change from baseline (cholesterol level at the start of IS tapering) to each annual visit. M12 and M24 visits represent Medium Frequency visits; L12 and L24 represent low frequency visits, and E12-48 represent extended follow-up visits. |
| Percent Change From Baseline in Blood Glucose | Enrollment through end of study (up to 9.5 years) | Glucose, a sugar, is an energy source that the body relies on to properly function. If levels are too high for a long period of time, diabetes can develop. Diabetes can result in many long-term complications such as eye, kidney, and nerve damage, stroke, and cardiovascular complications. The outcome looks at the percent change from baseline (glucose level at the start of tapering) to each annual visit. M12 and M24 visits represent Medium Frequency visits; L12 and L24 represent low frequency visits, and E12-48 represent extended follow-up visits. |
| Percent Change From Baseline in Systolic Blood Pressure | Enrollment through end of study (up to 9.5 years) | Systolic blood pressure (BP) measures the pressure on the blood vessels when the heart is beats and thus is pushing blood to the rest of the body. This outcome assesses the percent change from baseline (systolic blood pressure measurement at the start of tapering) to each annual visit. M12 and M24 visits represent Medium Frequency visits; L12 and L24 represent low frequency visits, and E12-48 represent extended follow-up visits. |
| Percent Change From Baseline in Diastolic Blood Pressure | Enrollment through end of study (up to 9.5 years) | Diastolic blood pressure (BP) measures the pressure in the arteries when the heart is a rest and is thus filled with blood. This outcome assesses the percent change from baseline (diastolic blood pressure measurement at the start of IS tapering) to each annual visit. M12 and M24 visits represent Medium Frequency visits; L12 and L24 represent low frequency visits, and E12-48 represent extended follow-up visits. |
| Percent Change From Baseline in Renal Function Measured by the Glomerular Filtration Rate (GFR) | Enrollment through end of study (up to 9.5 years) | Percent change from baseline at each annual visit. The bedside Schwartz equation was used to estimate GFR from serum creatinine and height in children. Baseline serum creatinine was utilized in the equation, defined as the creatinine value at the start of IS tapering. Baseline height was utilized in the equation, defined as the last height recorded prior to the start of IS tapering. Serum creatinine measurements and height measurements at the annual visits were used to calculate the annual GFR. When height value was not available, the height collected prior to the annual visit was used in the GFR calculation. M12 and M24 visits represent Medium Frequency visits; L12 and L24 represent low frequency visits, and E12-48 represent extended follow-up visits. |
Countries
United States
Participant flow
Recruitment details
Three centers in the United States enrolled 20 pediatric recipients of parental living-donor liver allografts between June 2006 and August 2008.
Pre-assignment details
Informed consent was obtained from eligible individuals prior to screening assessments. Participants then underwent procedures at screening to determine eligibility according to the study's inclusion/exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Immunosuppression Withdrawal Arm Participants were gradually tapered off of their single immunosuppression (IS) drug (cyclosporine or tacrolimus), over a 36 week period by first reducing the drug dose and then the dosing frequency until the participant was completely withdrawn from all immunosuppression. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Immunosuppression Withdrawal Arm |
|---|---|
| Age, Categorical <=18 years | 20 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 8.7 Years STANDARD_DEVIATION 2.96 |
| Baseline Diastolic Blood Pressure | 64.5 mmHg |
| Baseline Glomerular Filtration Rate (GFR) | 113.2 mL/min/1.73 m^2 |
| Baseline Glucose | 89.5 mg/dL |
| Baseline Systolic Blood Pressure | 109.5 mmHg |
| Baseline Total Cholesterol | 147 mg/dL |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Region of Enrollment United States | 20 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 19 / 20 |
| serious Total, serious adverse events | 13 / 20 |
Outcome results
Primary
Proportion of Participants Successfully Withdrawn From Immunosuppression
Participants were considered successfully withdrawn from immunosuppression if they remained off immunosuppression for at least one year with normal allograft function.
Time frame: 1 year after completion of immunosuppression withdrawal
Population: Intent-to-Treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immunosuppression Withdrawal Arm | Proportion of Participants Successfully Withdrawn From Immunosuppression | 0.60 Proportion of participants |
Comparison: The proportion of participants in whom immunosuppression withdrawal was attempted who are successfully withdrawn from immunosuppression are descriptively summarized with 95% confidence intervals using an exact binomial method95% CI: [0.4, 0.8]
Secondary
Distribution of Histologic Severity Among Rejection Episodes
The number of participants within each level of histologic severity based on BANFF grading criteria (Mild, Moderate, Severe).
Time frame: Start of immunosuppressive withdrawal to rejection through end of study (up to 9.5 years)
Population: Participants from the Intent-to-treat group who experienced a biopsy-proven rejection episode
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Immunosuppression Withdrawal Arm | Distribution of Histologic Severity Among Rejection Episodes | Mild | 3 Biopsy Proven rejection episodes |
| Immunosuppression Withdrawal Arm | Distribution of Histologic Severity Among Rejection Episodes | Moderate | 2 Biopsy Proven rejection episodes |
| Immunosuppression Withdrawal Arm | Distribution of Histologic Severity Among Rejection Episodes | Severe | 0 Biopsy Proven rejection episodes |
Secondary
Immunosuppression-Free Duration
The number of months between the end of immunosuppression withdrawal and either the end of trial participation or the time of restarting immunosuppression
Time frame: Completion of Withdrawal to either end of trial participation (up to 9.5 years) or time to restarting immunosuppression
Population: Intent-to-Treat participants who completed withdrawal
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Immunosuppression Withdrawal Arm | Immunosuppression-Free Duration | 75.84 Months |
Secondary
Number of Participants Experiencing Adverse Events by Severity
The results provide the total number of participants experiencing adverse events (AEs). Participants experiencing AEs are stratified into five severity categories: mild, moderate, severe, life-threatening, and death, based on National Cancer Institute--Common Terminology Criteria (NCI-CTCAE) Version 3.0.
Time frame: Enrollment through end of study (up to 9.5 years)
Population: Intent-To-Treat
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Immunosuppression Withdrawal Arm | Number of Participants Experiencing Adverse Events by Severity | Total Adverse Events | 19 Participants |
| Immunosuppression Withdrawal Arm | Number of Participants Experiencing Adverse Events by Severity | Mild | 18 Participants |
| Immunosuppression Withdrawal Arm | Number of Participants Experiencing Adverse Events by Severity | Moderate | 17 Participants |
| Immunosuppression Withdrawal Arm | Number of Participants Experiencing Adverse Events by Severity | Severe | 6 Participants |
| Immunosuppression Withdrawal Arm | Number of Participants Experiencing Adverse Events by Severity | Life Threatening | 0 Participants |
| Immunosuppression Withdrawal Arm | Number of Participants Experiencing Adverse Events by Severity | Death | 0 Participants |
Secondary
Number of Participants Who Suffered Graft Loss or Died Following Initiation of Immunosuppression Withdrawal
Participants who died while on the study for any reason as well as participants that experienced the loss of their transplant while a participant in the study.
Time frame: Enrollment through end of study (up to 9.5 years)
Population: Intent-to-Treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immunosuppression Withdrawal Arm | Number of Participants Who Suffered Graft Loss or Died Following Initiation of Immunosuppression Withdrawal | 0 Participants |
Comparison: The proportion of participants in whom immunosuppression (IS) withdrawal was attempted who are successfully withdrawn from immunosuppression and experience death or graft loss are descriptively summarized with 95% confidence intervals using an exact binomial method.95% CI: [0, 0.1684]
Secondary
Percent Change From Baseline in Blood Glucose
Glucose, a sugar, is an energy source that the body relies on to properly function. If levels are too high for a long period of time, diabetes can develop. Diabetes can result in many long-term complications such as eye, kidney, and nerve damage, stroke, and cardiovascular complications. The outcome looks at the percent change from baseline (glucose level at the start of tapering) to each annual visit. M12 and M24 visits represent Medium Frequency visits; L12 and L24 represent low frequency visits, and E12-48 represent extended follow-up visits.
Time frame: Enrollment through end of study (up to 9.5 years)
Population: Intent-To-Treat with glucose data available at visit
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Blood Glucose | Percent Change in Glucose at E12 Visit | -3.3 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Blood Glucose | Percent Change in Glucose at E24 Visit | -1.1 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Blood Glucose | Percent Change in Glucose at Month 12 | -2.2 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Blood Glucose | Percent Change in Glucose at M12 Visit | 1.0 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Blood Glucose | Percent Change in Glucose at M24 Visit | 1.8 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Blood Glucose | Percent Change in Glucose at L12 Visit | -0.5 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Blood Glucose | Percent Change in Glucose at L24 Visit | 2.0 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Blood Glucose | Percent Change in Glucose at E36 Visit | 5.6 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Blood Glucose | Percent Change in Glucose at E48 Visit | -5.3 Percent change |
Secondary
Percent Change From Baseline in Diastolic Blood Pressure
Diastolic blood pressure (BP) measures the pressure in the arteries when the heart is a rest and is thus filled with blood. This outcome assesses the percent change from baseline (diastolic blood pressure measurement at the start of IS tapering) to each annual visit. M12 and M24 visits represent Medium Frequency visits; L12 and L24 represent low frequency visits, and E12-48 represent extended follow-up visits.
Time frame: Enrollment through end of study (up to 9.5 years)
Population: Intent-to-treat with diastolic blood pressure data available at visit
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Diastolic Blood Pressure | Percent Change in Diastolic BP at E24 Visit | 2.6 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Diastolic Blood Pressure | Percent Change in Diastolic BP at E36 Visit | -1.4 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Diastolic Blood Pressure | Percent Change in Diastolic BP at E48 | 9.1 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Diastolic Blood Pressure | Percent Change in Diastolic BP at Month 12 | -7.5 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Diastolic Blood Pressure | Percent Change in Diastolic BP atM12 Visit | 0.0 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Diastolic Blood Pressure | Percent Change in Diastolic BP at M24 Visit | -5.4 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Diastolic Blood Pressure | Percent Change in Diastolic BP at L12 Visit | 1.5 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Diastolic Blood Pressure | Percent Change in Diastolic BP at L24 Visit | 6.6 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Diastolic Blood Pressure | Percent Change in Diastolic BP at E12 Visit | 0.0 Percent change |
Secondary
Percent Change From Baseline in Renal Function Measured by the Glomerular Filtration Rate (GFR)
Percent change from baseline at each annual visit. The bedside Schwartz equation was used to estimate GFR from serum creatinine and height in children. Baseline serum creatinine was utilized in the equation, defined as the creatinine value at the start of IS tapering. Baseline height was utilized in the equation, defined as the last height recorded prior to the start of IS tapering. Serum creatinine measurements and height measurements at the annual visits were used to calculate the annual GFR. When height value was not available, the height collected prior to the annual visit was used in the GFR calculation. M12 and M24 visits represent Medium Frequency visits; L12 and L24 represent low frequency visits, and E12-48 represent extended follow-up visits.
Time frame: Enrollment through end of study (up to 9.5 years)
Population: Intent-To-Treat with GFR data at visits available for analysis
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Renal Function Measured by the Glomerular Filtration Rate (GFR) | Percent Change in GFR at M12 Visit | 8.7 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Renal Function Measured by the Glomerular Filtration Rate (GFR) | Percent Change in GFR at M24 Visit | 20.5 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Renal Function Measured by the Glomerular Filtration Rate (GFR) | Percent Change in GFR at Month 12 | 4.5 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Renal Function Measured by the Glomerular Filtration Rate (GFR) | Percent Change in GFR at L12 Visit | 10.8 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Renal Function Measured by the Glomerular Filtration Rate (GFR) | Percent Change in GFR at L24 Visit | 7.3 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Renal Function Measured by the Glomerular Filtration Rate (GFR) | Percent Change in GFR at E12 Visit | -3.9 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Renal Function Measured by the Glomerular Filtration Rate (GFR) | Percent Change in GFR at E24 Visit | -6.3 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Renal Function Measured by the Glomerular Filtration Rate (GFR) | Percent Change in GFR at E36 Visit | -5.1 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Renal Function Measured by the Glomerular Filtration Rate (GFR) | Percent Change in GFR at E48 Visit | -15.1 Percent change |
Secondary
Percent Change From Baseline in Systolic Blood Pressure
Systolic blood pressure (BP) measures the pressure on the blood vessels when the heart is beats and thus is pushing blood to the rest of the body. This outcome assesses the percent change from baseline (systolic blood pressure measurement at the start of tapering) to each annual visit. M12 and M24 visits represent Medium Frequency visits; L12 and L24 represent low frequency visits, and E12-48 represent extended follow-up visits.
Time frame: Enrollment through end of study (up to 9.5 years)
Population: Intent-to-treat with systolic blood pressure data available at visit
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Systolic Blood Pressure | Percent Change in Systolic BP at Month 12 | 2.0 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Systolic Blood Pressure | Percent Change in Systolic BP at M12 Visit | 0.0 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Systolic Blood Pressure | Percent Change in Systolic BP at M24 | 4.3 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Systolic Blood Pressure | Percent Change in Systolic BP at L12 Visit | 3.8 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Systolic Blood Pressure | Percent Change in Systolic BP at L24 Visit | 8.6 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Systolic Blood Pressure | Percent Change in Systolic BP at E12 Visit | 2.8 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Systolic Blood Pressure | Percent Change in Systolic BP at E24 Visit | 5.1 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Systolic Blood Pressure | Percent Change in Systolic BP at E36 Visit | 9.2 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Systolic Blood Pressure | Percent Change in Systolic BP at E48 Visit | 2.7 Percent change |
Secondary
Percent Change From Baseline in Total Cholesterol
Percent change from baseline in total serum cholesterol. Cholesterol is a waxy substance your body needs to build cells, but too much can be a problem since it can build-up in arteries. Narrowed arteries can result in heart attack or stroke. This outcome looks at the percent change from baseline (cholesterol level at the start of IS tapering) to each annual visit. M12 and M24 visits represent Medium Frequency visits; L12 and L24 represent low frequency visits, and E12-48 represent extended follow-up visits.
Time frame: Enrollment through end of study (up to 9.5 years)
Population: Intent-To-Treat with cholesterol data available at visit
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Total Cholesterol | Percent Change in Cholesterol at Month 12 | -7.9 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Total Cholesterol | Percent Change in Cholesterol at M12 Visit | -0.6 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Total Cholesterol | Percent Change in Cholesterol at M24 Visit | -10.9 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Total Cholesterol | Percent Change in Cholesterol at L12 Visit | -3.0 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Total Cholesterol | Percent Change in Cholesterol at L24 Visit | -10.7 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Total Cholesterol | Percent Change in Cholesterol at E12 Visit | -9.0 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Total Cholesterol | Percent Change in Cholesterol at E24 Visit | -11.2 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Total Cholesterol | Percent Change in Cholesterol at E36 Visit | -6.9 Percent change |
| Immunosuppression Withdrawal Arm | Percent Change From Baseline in Total Cholesterol | Percent Change in Cholesterol at E48 Visit | -10.9 Percent change |
Secondary
Time From Start of Immunosuppression Withdrawal to the First Episode of Acute Rejection, Second Episode of Rejection That Did Not Require Treatment, or to Diagnosis of Chronic Rejection
The number of days between the start of immunosuppression (IS) withdrawal and the first episode of acute rejection (either clinical rejection or based on BANFF criteria), second episode of rejection that did not require treatment, or the first diagnosis of chronic rejection.
Time frame: From the start of immunosuppression withdrawal to first acute rejection, second episode of rejection that did not require treatment, or diagnosis of chronic rejection through end of study (up to 9.5 years)
Population: Intent-to-Treat participants who experienced acute rejection or were diagnosed with chronic rejection.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Immunosuppression Withdrawal Arm | Time From Start of Immunosuppression Withdrawal to the First Episode of Acute Rejection, Second Episode of Rejection That Did Not Require Treatment, or to Diagnosis of Chronic Rejection | 211.57 Days |