A Phase 2 interventional study of Immunosuppression withdrawal in Liver Transplant and Liver Transplantation, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 7 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-09-14.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 2, Interventional, and Treatment
The primary aim of this study is to determine whether a peripheral blood or graft lymphocyte phenotype of immune senescence or exhaustion is different between operationally tolerant and non-tolerant liver allograft recipients.
People who have liver transplants must take anti-rejection medication (immunosuppression) for the rest of their lives. If they stop, their immune system may reject the transplanted liver. All anti-rejection medications have side effects. Because of the side effects of anti-rejection medications, an important goal of transplant research is to allow people to accept their transplanted organ without long term use of anti-rejection medications. This is called tolerance. In this study, participants who received a liver transplant will have their anti-rejection medication(s) gradually reduced over a period of time and then stopped. The study calls this 'immunosuppression withdrawal'.
The purpose of this research study is to see how many people will develop tolerance after immunosuppression withdrawal. The researchers also want to find out if there are blood or liver biopsy tests that can help transplant doctors in the future predict whether it is safe to decrease or stop anti-rejection medications in people who received a liver transplant.
National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,401 studies on the registry; 179 are open to participants now.
Of its 396 completed or terminated interventional studies of FDA-regulated products, 294 (74%) have results posted.
Counted across the registry records on this site, refreshed daily.
Recipient participants must meet all of the following criteria to be eligible for this study:
At the time of screening:
Must have a screening liver biopsy that fulfills the following criteria based on the central pathology reading:
Receiving calcineurin inhibitor (CNI) based maintenance immunosuppression. Participants may also concurrently receive:
Living donor participants must meet all of the following criteria to be eligible for this study:
Exclusion Criteria:
Recipient participants who meet any of the following criteria will not be eligible for this study:
Prospective baseline liver biopsy showing any of the following: (see recipient inclusion criteria #4)
Living donor participants who meet any of the following criteria will not be eligible for this study:
Gradual immunosuppression withdrawal according to the protocol defined algorithm
Biological: Immunosuppression withdrawal
Participants will initiate calcineurin inhibitor (CNI) withdrawal after at least 3 weeks of stable liver function, as documented by liver function tests (direct bilirubin, alanine aminotransferase and gamma-glutamyl transferase) separated by at least 1 week in the 3 week period prior to withdrawal. CNI withdrawal will occur in eight 3 week intervals with each subsequent reduction based on liver function tests over the prior 3 week interval. Participants on CNI and prednisone will undergo withdrawal from the two therapies concurrently. If participants are weaned off the CNI successfully, they will initiate non-CNI withdrawal. The non-CNI withdrawal includes two dose reductions of approximately 50% over a 6 week period each, after which the drug will be discontinued.
Also known as: ISW
The Percent of Participants Who Achieve Operational Tolerance 52 Weeks After Completion of Immunosuppression Withdrawal.
Participants are considered as successfully withdrawn from immunosuppression if they remain off immunosuppression for at least 52 weeks without evidence of rejection since enrollment and have a liver biopsy at 52 weeks following completion of immunosuppression withdrawal demonstrating histological stability and the absence of rejection per Banff global assessment criteria. This biopsy is assessed by the central pathologist. All participants who fail to complete immunosuppression withdrawal, regardless of reason, or fail to have a biopsy 52 weeks after completion of immunosuppression withdrawal will be considered to have failed.
Time frame: From initiation of immunosuppression withdrawal through 52 weeks after stopping all immunosuppression
Proportion of Participants Who Develop Donor-Specific AlloAbs (DSA) or de Novo Anti-human Leukocyte Antigen Human Leukocyte Antigen (HLA) Antibodies
HLA is a molecule formed by a complex of genes which encode cell-surface proteins responsible for the regulation of the immune system. This molecule is unique for each individual. HLA molecules are present in all cells and are responsible for helping the immune system distinguish between your own cells and foreign cells (like pathogens). However, when our immune system encounters HLA molecules from another individual (like during pregnancy, after blood transfusions or transplantation) it recognizes this as foreign and can generate anti-HLA antibodies. These anti-HLA antibodies could cause harm to the transplanted organ by recognizing its cells as foreign triggering the immune system to attack. This endpoint looks at the development of newly developed donor-specific antibodies (DSA). DSA are a subset of anti-HLA antibodies that are specific against the donor organ. These anti-HLA antibodies are categorized into two classes-class I and class II. The data shown is only for class II DSA.
Time frame: From initiation of immunosuppression withdrawal to study completion, up to 4.5 years.
The Incidence of Acute Rejection, Steroid Resistant Rejection, and Chronic Rejection
Incidence will be measured as the proportion of participants who have acute rejection (per Banff criteria), steroid resistant rejection (rejection requiring antibody treatment), and chronic rejection (per Banff criteria), separately. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval.
Time frame: From initiation of immunosuppression withdrawal to study completion, up to 4.5 years.
The Severity of Acute Rejection, Steroid Resistant Rejection, and Chronic Rejection
Severity is based on the Banff global assessment grade according to the central pathology reading of the liver biopsy. For an individual subject, the worst severity is reported. Acute rejection is categorized into mild (rejection infiltrate in a minority of triads that is generally mild and confined within the portal spaces), moderate (rejection infiltrate expanding most or all of the triads), or severe (rejection infiltrate expanding most or all of the triads with spillover into periportal areas and moderate to severe perivenular inflammation that extends into the hepatic parenchyma and is associated with perivenular hepatocyte necrosis). Chronic rejection is categorized into early (bile duct atrophy/loss and foam cell obliterative arteriopathy in \<50% of the portal tracts) or late (early criteria but \>50% of the portal tracts) stage. Steroid resistant rejection is always considered severe. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval.
Time frame: From initiation of immunosuppression withdrawal to study completion, up to 4.5 years.
The Timing of Acute Rejection, Steroid Resistant Rejection, and Chronic Rejection
Time is measured as the time (in days) from the initiation of immunosuppression withdrawal to the time of the first biopsy showing rejection (per Banff criteria).
Time frame: From initiation of immunosuppression withdrawal to study completion, up to 4.5 years.
The Incidence of Graft Fibrosis in Tolerant Versus Non- Tolerant Patients.
Fibrosis of the liver is the formation of an excessive accumulation of scar tissue in the liver. Graft fibrosis was measured two ways by the ISHAK scale and by Liver Allograft Fibrosis Score (LAFSc) via a liver biopsy. Both scales range from 0 to 6, with a higher score indicating more severe fibrosis. A subject is considered as having graft fibrosis if the score is greater than or equal to 2 at their last available biopsy after the initiation of immunosuppression withdrawal.
Time frame: From initiation of immunosuppression withdrawal to study completion, up to 4.5 years.
The Progression of Graft Fibrosis in Tolerant Versus Non- Tolerant Patients
Fibrosis of the liver is the formation of an excessive accumulation of scar tissue in the liver. Graft fibrosis was measured two ways by the ISHAK scale and by Liver Allograft Fibrosis Score (LAFSc) via a liver biopsy. Both scales range from 0 to 6, with a higher score indicating more severe fibrosis. Progression was calculated as the final available biopsy score minus the baseline biopsy score. A positive value indicates a worsening of fibrosis.
Time frame: From initiation of immunosuppression withdrawal to study completion, up to 4.5 years.
The Incidence of Graft Loss
A participant is considered to have graft loss when the donated liver needs to be removed and the participant is retransplanted with another donor liver or the participant is listed for retransplant. The endpoint will be summarized with a two-sided, 95% exact binomial confidence interval.
Time frame: From initiation of immunosuppression withdrawal to study completion, up to 4.5 years.
The Incidence of All-Cause Mortality
This number reflects all deaths observed in all participants in the study period, regardless of the cause. The endpoint will be summarized with a two-sided, 95% exact binomial confidence interval.
Time frame: From initiation of immunosuppression withdrawal to study completion, up to 4.5 years.
The Incidence of Study-related SAEs
An adverse event is considered a serious adverse event (SAE) if it results it any one of the following: death, life-threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substation disruption to conduct normal life functions, congenital anomaly or birth defect, or an important medical event. The event is considered study related if the medical monitor deems it to be at least possibly or definitely related to any of the study interventions/procedures (immunosuppression withdrawal, the blood draw, or the liver biopsy). The endpoint will be summarized with a two-sided, 95% exact binomial confidence interval.
Time frame: From initiation of immunosuppression withdrawal to study completion, up to 4.5 years.
The Proportion of Operationally Tolerant Subjects Who Remain Free of Rejection at 3 Years After Completing Immunosuppression Withdrawal.
Participants are considered operationally tolerant if they remain off immunosuppression for at least 52 weeks without evidence of rejection since enrollment and have a liver biopsy at 52 weeks following completion of immunosuppression withdrawal demonstrating histological stability and the absence of rejection per Banff global assessment criteria (as assessed by the central pathologist). This number reflects the participants that continue to show the absence of rejection per the Banff global assessment criteria (as assessed by the central pathologist) in the 3 years following completion of immunosuppression withdrawal. The endpoint will be summarized with a two-sided, 95% exact binomial confidence interval.
Time frame: From initiation of immunosuppression withdrawal through 3 years after completing immunosuppression withdrawal.
Changes in Renal Function (Defined as Estimated GFR Calculated by the CKD-EPI Creatine Equation 2021) in Tolerant Versus Non-tolerant Participants at 1, 2 and 3 Years After Completing Immunosuppression Withdrawal.
Glomerular filtration rate (GFR) is a measure of kidney function and helps determine the stage of kidney disease. A value less than 15 indicates kidney failure, 15 to 29 indicates severe loss of kidney function, 30 to 44 indicates moderate to severe loss of kidney function, 45 to 59 mild to moderate loss of kidney function, 60 to 89 indicates mild loss of kidney function, and 90 or higher indicates normal kidney function. The equation developed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) is used to estimate GFR from serum creatinine. The baseline value was selected as the value collected immediately prior to the initiation of immunosuppression withdrawal. The year 1, 2, and 3, values are the values closest to and within 2 months of the expected date. Change was calculated as the year 1, 2, or 3 value minus baseline. A positive value indicates an increase in kidney function.
Time frame: From initiation of immunosuppression withdrawal to study completion, up to 4.5 years.
Changes in Quality of Life in Tolerant Versus Non-tolerant Participants and in All Participants at Baseline Versus the End of Study Participation, as Measured by the NIDDK Liver Transplantation Database Quality of Life Form.
NIDDK Liver Transplantation Database Quality of Life Form is a patient-reported survey of patient health. The questionnaire is summarized into five domains-measures of disease (ranges from 0-21 with higher score indicating worse quality), psychological status (ranges from 0-5 with higher score indicating worse quality), personal function (ranges from 0-4 with higher score indicating better quality), social and role function (ranges from 0 to 20 with higher score indicating worse quality), and general health perception (ranges from 0 to 10 with higher score indicating better quality). Change was calculated as the difference between the questionnaire completed at the initiation of withdrawal and the questionnaire completed closest to the end of study participation. This change was calculated separately for tolerant and non-tolerant subjects.
Time frame: From initiation of immunosuppression withdrawal to study completion, up to 4.5 years.
Changes in SF-36 in Tolerant Versus Non-tolerant Participants and in All Participants at Baseline Versus the End of Study Participation.
SF-36 is a patient-reported survey of patient health. There are eight different scales that can be summarized into two summary scores-Mental Component Score and Physical Component Score. Each score ranges from 0-100, with a higher score indicating a better quality of life. Change was calculated as the difference between the questionnaire completed at the initiation of withdrawal and the questionnaire completed closest to the end of study participation. This change was calculated separately for tolerant and non-tolerant subjects.
Time frame: From initiation of immunosuppression withdrawal to study completion, up to 4.5 years.
Predictive Value of the Following Parameters With Regard to Operational Tolerance: Time Post-transplant.
Time post-transplant is calculated as time in years from transplant to enrollment. Participants are considered operationally tolerant if they remain off immunosuppression for at least 52 weeks without evidence of rejection since enrollment and have a liver biopsy at 52 weeks following completion of immunosuppression withdrawal demonstrating histological stability and the absence of rejection per Banff global assessment criteria (as assessed by the central pathologist). The odds ratio and corresponding 95% confidence interval are presented. The odds ratio represents the probability of achieving operational tolerance per year increase in time post-transplant. An odds ratio greater than 1 means that as the factor increases, operational tolerance is more likely to occur. Whereas less than 1 means operational tolerance is less likely to occur. Since the confidence interval contains 1, this means that as the corresponding factor increases, the likelihood of tolerance does not change.
Time frame: From initiation of immunosuppression withdrawal to study completion, up to 4.5 years.
Predictive Value and the Correlative Value of the Following Parameters With Regard to Operational Tolerance: Recipient Age.
Recipient age is the age at the time of enrollment. Participants are considered operationally tolerant if they remain off immunosuppression for at least 52 weeks without evidence of rejection since enrollment and have a liver biopsy at 52 weeks following completion of immunosuppression withdrawal demonstrating histological stability and the absence of rejection per Banff global assessment criteria (as assessed by the central pathologist). The odds ratio and corresponding 95% confidence interval are presented. The odds ratio represents the probability of achieving operational tolerance per year increase in recipient age. An odds ratio greater than 1 means that as the factor increases, operational tolerance is more likely to occur. Whereas less than 1 means operational tolerance is less likely to occur. Since the confidence interval contains 1, this means that as the corresponding factor increases, the likelihood of tolerance does not change.
Time frame: From initiation of immunosuppression withdrawal to study completion, up to 4.5 years.
100 participants were enrolled from 7 sites in the US between December 2015 and November 2018. 61 of the enrolled participants were eligible to initiate immunosuppression withdrawal and the remaining 39 participants were terminated (e.g., ineligible to initiate immunosuppression withdrawal) based on biopsy findings or other pre-specified criteria.
| Milestone | Enrolled, Did Not Initiate Immunosuppression Withdrawal | Initiated Immunosuppression Withdrawal |
|---|---|---|
| Started | 39 | 61 |
| Completed | 0 | 50 |
| Not completed | 39 | 11 |
| Withdrew: Death | 0 | 2 |
| Withdrew: Lost to follow-up | 0 | 1 |
| Withdrew: Physician decision | 0 | 1 |
| Withdrew: Withdrawal by subject | 2 | 5 |
| Withdrew: Screen failure | 37 | 0 |
| Withdrew: Protocol deviation | 0 | 1 |
| Withdrew: Non-compliance | 0 | 1 |
Participants are considered as successfully withdrawn from immunosuppression if they remain off immunosuppression for at least 52 weeks without evidence of rejection since enrollment and have a liver biopsy at 52 weeks following completion of immunosuppression withdrawal demonstrating histological stability and the absence of rejection per Banff global assessment criteria. This biopsy is assessed by the central pathologist. All participants who fail to complete immunosuppression withdrawal, regardless of reason, or fail to have a biopsy 52 weeks after completion of immunosuppression withdrawal will be considered to have failed.
| Percent of Participants | Immunosuppression Withdrawal (ISW) |
|---|---|
| The Percent of Participants Who Achieve Operational Tolerance 52 Weeks After Completion of Immunosuppression Withdrawal. | 16.4 (8.15 to 28.1) |
HLA is a molecule formed by a complex of genes which encode cell-surface proteins responsible for the regulation of the immune system. This molecule is unique for each individual. HLA molecules are present in all cells and are responsible for helping the immune system distinguish between your own cells and foreign cells (like pathogens). However, when our immune system encounters HLA molecules from another individual (like during pregnancy, after blood transfusions or transplantation) it recognizes this as foreign and can generate anti-HLA antibodies. These anti-HLA antibodies could cause harm to the transplanted organ by recognizing its cells as foreign triggering the immune system to attack. This endpoint looks at the development of newly developed donor-specific antibodies (DSA). DSA are a subset of anti-HLA antibodies that are specific against the donor organ. These anti-HLA antibodies are categorized into two classes-class I and class II. The data shown is only for class II DSA.
| Percent of participants | Immunosuppression Withdrawal (ISW) |
|---|---|
| Proportion of Participants Who Develop Donor-Specific AlloAbs (DSA) or de Novo Anti-human Leukocyte Antigen Human Leukocyte Antigen (HLA) Antibodies | 26.9 (15.57 to 41.02) |
Incidence will be measured as the proportion of participants who have acute rejection (per Banff criteria), steroid resistant rejection (rejection requiring antibody treatment), and chronic rejection (per Banff criteria), separately. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval.
| Percent of participants | Immunosuppression Withdrawal (ISW) |
|---|---|
| Acute Rejection | 47.5 (34.60 to 60.73) |
| Steroid Resistant Rejection | 0 (0 to 5.87) |
| Chronic Rejection | 0 (0 to 5.87) |
Severity is based on the Banff global assessment grade according to the central pathology reading of the liver biopsy. For an individual subject, the worst severity is reported. Acute rejection is categorized into mild (rejection infiltrate in a minority of triads that is generally mild and confined within the portal spaces), moderate (rejection infiltrate expanding most or all of the triads), or severe (rejection infiltrate expanding most or all of the triads with spillover into periportal areas and moderate to severe perivenular inflammation that extends into the hepatic parenchyma and is associated with perivenular hepatocyte necrosis). Chronic rejection is categorized into early (bile duct atrophy/loss and foam cell obliterative arteriopathy in \<50% of the portal tracts) or late (early criteria but \>50% of the portal tracts) stage. Steroid resistant rejection is always considered severe. The endpoint is summarized with a two-sided, 95% exact binomial confidence interval.
| Percent of participants | Participants With Rejection |
|---|---|
| Acute Rejection, Mild | 75.9 (56.46 to 89.70) |
| Acute Rejection, Moderate | 20.7 (7.99 to 39.72) |
| Acute Rejection, Severe | 3.5 (0.09 to 17.76) |
| Chronic Rejection, Early Stage | 0 (0 to 11.94) |
| Chronic Rejection, Late Stage | 0 (0 to 11.94) |
| Steroid Resistant Rejection | 0 (0 to 11.94) |
Time is measured as the time (in days) from the initiation of immunosuppression withdrawal to the time of the first biopsy showing rejection (per Banff criteria).
| Days | Participants With Rejection |
|---|---|
| The Timing of Acute Rejection | 232 ± 134.5 |
Fibrosis of the liver is the formation of an excessive accumulation of scar tissue in the liver. Graft fibrosis was measured two ways by the ISHAK scale and by Liver Allograft Fibrosis Score (LAFSc) via a liver biopsy. Both scales range from 0 to 6, with a higher score indicating more severe fibrosis. A subject is considered as having graft fibrosis if the score is greater than or equal to 2 at their last available biopsy after the initiation of immunosuppression withdrawal.
| Percent of participants | Initiated Immunosuppression Withdrawal With Available Biopsy (Tolerant) | Initiated Immunosuppression Withdrawal With Available Biopsy (Non-tolerant) |
|---|---|---|
| ISHAK | 0 (0 to 30.85) | 12.2 (4.08 to 26.20) |
| Liver Allograft Fibrosis Score | 50.0 (18.71 to 81.29) | 48.8 (32.88 to 64.87) |
Fibrosis of the liver is the formation of an excessive accumulation of scar tissue in the liver. Graft fibrosis was measured two ways by the ISHAK scale and by Liver Allograft Fibrosis Score (LAFSc) via a liver biopsy. Both scales range from 0 to 6, with a higher score indicating more severe fibrosis. Progression was calculated as the final available biopsy score minus the baseline biopsy score. A positive value indicates a worsening of fibrosis.
| Fibrosis Score | Initiated Immunosuppression Withdrawal With Available Biopsy (Tolerant) | Initiated Immunosuppression Withdrawal With Available Biopsy (Non-tolerant) |
|---|---|---|
| ISHAK | 0 ± 0.94 | 0.2 ± 0.79 |
| Liver Allograft Fibrosis Score | 0.1 ± 1.73 | 0.3 ± 1.44 |
A participant is considered to have graft loss when the donated liver needs to be removed and the participant is retransplanted with another donor liver or the participant is listed for retransplant. The endpoint will be summarized with a two-sided, 95% exact binomial confidence interval.
| Percent of participants | Immunosuppression Withdrawal (ISW) |
|---|---|
| The Incidence of Graft Loss | 0 (0 to 5.87) |
This number reflects all deaths observed in all participants in the study period, regardless of the cause. The endpoint will be summarized with a two-sided, 95% exact binomial confidence interval.
| Percent of participants | Immunosuppression Withdrawal (ISW) |
|---|---|
| The Incidence of All-Cause Mortality | 3.3 (0.40 to 11.35) |
An adverse event is considered a serious adverse event (SAE) if it results it any one of the following: death, life-threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substation disruption to conduct normal life functions, congenital anomaly or birth defect, or an important medical event. The event is considered study related if the medical monitor deems it to be at least possibly or definitely related to any of the study interventions/procedures (immunosuppression withdrawal, the blood draw, or the liver biopsy). The endpoint will be summarized with a two-sided, 95% exact binomial confidence interval.
| Percent of participants | Immunosuppression Withdrawal (ISW) |
|---|---|
| The Incidence of Study-related SAEs | 16.4 (8.15 to 28.09) |
Participants are considered operationally tolerant if they remain off immunosuppression for at least 52 weeks without evidence of rejection since enrollment and have a liver biopsy at 52 weeks following completion of immunosuppression withdrawal demonstrating histological stability and the absence of rejection per Banff global assessment criteria (as assessed by the central pathologist). This number reflects the participants that continue to show the absence of rejection per the Banff global assessment criteria (as assessed by the central pathologist) in the 3 years following completion of immunosuppression withdrawal. The endpoint will be summarized with a two-sided, 95% exact binomial confidence interval.
| Percent of participants | Operationally Tolerant |
|---|---|
| The Proportion of Operationally Tolerant Subjects Who Remain Free of Rejection at 3 Years After Completing Immunosuppression Withdrawal. | 100 (69.15 to 100) |
Glomerular filtration rate (GFR) is a measure of kidney function and helps determine the stage of kidney disease. A value less than 15 indicates kidney failure, 15 to 29 indicates severe loss of kidney function, 30 to 44 indicates moderate to severe loss of kidney function, 45 to 59 mild to moderate loss of kidney function, 60 to 89 indicates mild loss of kidney function, and 90 or higher indicates normal kidney function. The equation developed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) is used to estimate GFR from serum creatinine. The baseline value was selected as the value collected immediately prior to the initiation of immunosuppression withdrawal. The year 1, 2, and 3, values are the values closest to and within 2 months of the expected date. Change was calculated as the year 1, 2, or 3 value minus baseline. A positive value indicates an increase in kidney function.
| ml/min/1.73 m^2 | Initiated Immunosuppression Withdrawal (Tolerant) | Initiated Immunosuppression Withdrawal (Non-tolerant) |
|---|---|---|
| 1 Yeaar | 4.8 ± 13.67 | 0 ± 13.85 |
| 2 Years | 4.2 ± 21.32 | -4.0 ± 12.19 |
| 3 year | -2.8 ± 18.11 | -2.6 ± 13.85 |
NIDDK Liver Transplantation Database Quality of Life Form is a patient-reported survey of patient health. The questionnaire is summarized into five domains-measures of disease (ranges from 0-21 with higher score indicating worse quality), psychological status (ranges from 0-5 with higher score indicating worse quality), personal function (ranges from 0-4 with higher score indicating better quality), social and role function (ranges from 0 to 20 with higher score indicating worse quality), and general health perception (ranges from 0 to 10 with higher score indicating better quality). Change was calculated as the difference between the questionnaire completed at the initiation of withdrawal and the questionnaire completed closest to the end of study participation. This change was calculated separately for tolerant and non-tolerant subjects.
| Domain Score | Initiated Immunosuppression Withdrawal (Tolerant) | Initiated Immunosuppression Withdrawal (Non-tolerant) |
|---|---|---|
| Measures of disease domain | -1.9 ± 5.69 | 0.5 ± 4.31 |
| Psychological status domain | -0.6 ± 2.07 | 0.2 ± 1.43 |
| Personal function domain | 0.1 ± 1.73 | -0.2 ± 1.14 |
| Social and role function domain | 1.7 ± 2.89 | 1.1 ± 2.92 |
| General health perception domain | -0.8 ± 2.11 | -0.5 ± 2.03 |
SF-36 is a patient-reported survey of patient health. There are eight different scales that can be summarized into two summary scores-Mental Component Score and Physical Component Score. Each score ranges from 0-100, with a higher score indicating a better quality of life. Change was calculated as the difference between the questionnaire completed at the initiation of withdrawal and the questionnaire completed closest to the end of study participation. This change was calculated separately for tolerant and non-tolerant subjects.
| SF-36 Component Score | Initiated Immunosuppression Withdrawal (Tolerant) | Initiated Immunosuppression Withdrawal (Non-tolerant) |
|---|---|---|
| Physical Component Score | -3.4 ± 8.75 | -1.9 ± 7.72 |
| Mental Component Score | 0.5 ± 9.75 | -0.7 ± 7.45 |
Time post-transplant is calculated as time in years from transplant to enrollment. Participants are considered operationally tolerant if they remain off immunosuppression for at least 52 weeks without evidence of rejection since enrollment and have a liver biopsy at 52 weeks following completion of immunosuppression withdrawal demonstrating histological stability and the absence of rejection per Banff global assessment criteria (as assessed by the central pathologist). The odds ratio and corresponding 95% confidence interval are presented. The odds ratio represents the probability of achieving operational tolerance per year increase in time post-transplant. An odds ratio greater than 1 means that as the factor increases, operational tolerance is more likely to occur. Whereas less than 1 means operational tolerance is less likely to occur. Since the confidence interval contains 1, this means that as the corresponding factor increases, the likelihood of tolerance does not change.
| Probability of operational tolerance | Immunosuppression Withdrawal (ISW) |
|---|---|
| Predictive Value of the Following Parameters With Regard to Operational Tolerance: Time Post-transplant. | 0.994 (0.864 to 1.144) |
Recipient age is the age at the time of enrollment. Participants are considered operationally tolerant if they remain off immunosuppression for at least 52 weeks without evidence of rejection since enrollment and have a liver biopsy at 52 weeks following completion of immunosuppression withdrawal demonstrating histological stability and the absence of rejection per Banff global assessment criteria (as assessed by the central pathologist). The odds ratio and corresponding 95% confidence interval are presented. The odds ratio represents the probability of achieving operational tolerance per year increase in recipient age. An odds ratio greater than 1 means that as the factor increases, operational tolerance is more likely to occur. Whereas less than 1 means operational tolerance is less likely to occur. Since the confidence interval contains 1, this means that as the corresponding factor increases, the likelihood of tolerance does not change.
| Probability of operational tolerance | Immunosuppression Withdrawal (ISW) |
|---|---|
| Predictive Value and the Correlative Value of the Following Parameters With Regard to Operational Tolerance: Recipient Age. | 0.982 (0.922 to 1.045) |
Collected over Up to 4.5 years. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Enrolled, Did Not Initiate Immunosuppression Withdrawal | 0/39 (0%) | 0/39 (0%) | 3/39 (7.7%) |
| Initiated Immunosuppression Withdrawal | 2/61 (3.3%) | 27/61 (44.3%) | 53/61 (86.9%) |
| Event | Enrolled, Did Not Initiate Immunosuppression Withdrawal | Initiated Immunosuppression Withdrawal |
|---|---|---|
| Transplant rejectionImmune system disorders | 0/39 | 5/61 |
| Small intestinal obstructionGastrointestinal disorders | 0/39 | 3/61 |
| CellulitisInfections and infestations | 0/39 | 3/61 |
| Abdominal herniaGastrointestinal disorders | 0/39 | 2/61 |
| Urinary tract infectionInfections and infestations | 0/39 | 2/61 |
| ArrhythmiaCardiac disorders | 0/39 | 1/61 |
| Atrial fibrillationCardiac disorders | 0/39 | 1/61 |
| Atrioventricular blockCardiac disorders | 0/39 | 1/61 |
| Atrioventricular block completeCardiac disorders | 0/39 | 1/61 |
| Cardiac failure acuteCardiac disorders | 0/39 | 1/61 |
| Event | Enrolled, Did Not Initiate Immunosuppression Withdrawal | Initiated Immunosuppression Withdrawal |
|---|---|---|
| Transplant rejectionImmune system disorders | 0/39 | 28/61 |
| Upper respiratory tract infectionInfections and infestations | 0/39 | 6/61 |
| Urinary tract infectionInfections and infestations | 0/39 | 5/61 |
| Transplant dysfunctionInjury, poisoning and procedural complications | 0/39 | 5/61 |
| Gamma-glutamyltransferase increasedInvestigations | 1/39 | 5/61 |
| Liver function test abnormalInvestigations | 0/39 | 5/61 |
| SinusitisInfections and infestations | 0/39 | 4/61 |
| DiarrhoeaGastrointestinal disorders | 0/39 | 3/61 |
| BronchitisInfections and infestations | 0/39 | 3/61 |
| DiverticulitisInfections and infestations | 0/39 | 3/61 |
| Age, Categorical(Participants) | Enrolled, Did Not Initiate Immunosuppression Withdrawal | Initiated Immunosuppression Withdrawal | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 31 | 37 | 68 |
| >=65 years | 8 | 24 | 32 |
| Age, Continuous(years) | Enrolled, Did Not Initiate Immunosuppression Withdrawal | Initiated Immunosuppression Withdrawal | Total |
|---|---|---|---|
| Mean | 51.0 ± 15.88 | 60.3 ± 12.07 | 56.7 ± 14.35 |
| Sex: Female, Male(Participants) | Enrolled, Did Not Initiate Immunosuppression Withdrawal | Initiated Immunosuppression Withdrawal | Total |
|---|---|---|---|
| Female | 15 | 18 | 33 |
| Male | 24 | 43 | 67 |
| Ethnicity (NIH/OMB)(Participants) | Enrolled, Did Not Initiate Immunosuppression Withdrawal | Initiated Immunosuppression Withdrawal | Total |
|---|---|---|---|
| Hispanic or Latino | 2 | 4 | 6 |
| Not Hispanic or Latino | 36 | 49 | 85 |
| Unknown or Not Reported | 1 | 8 | 9 |
| Race (NIH/OMB)(Participants) | Enrolled, Did Not Initiate Immunosuppression Withdrawal | Initiated Immunosuppression Withdrawal | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 1 | 6 | 7 |
| Native Hawaiian or Other Pacific Islander | 1 | 1 | 2 |
| Black or African American | 2 | 0 | 2 |
| White | 33 | 50 | 83 |
| More than one race | 0 | 1 | 1 |
| Unknown or Not Reported | 2 | 3 | 5 |
| Region of Enrollment(Participants) | Enrolled, Did Not Initiate Immunosuppression Withdrawal | Initiated Immunosuppression Withdrawal | Total |
|---|---|---|---|
| United States | 39 | 61 | 100 |
| Alanine Transaminase (ALT)(U/L) | Enrolled, Did Not Initiate Immunosuppression Withdrawal | Initiated Immunosuppression Withdrawal | Total |
|---|---|---|---|
| Mean | — | 23.8 ± 10.7 | 23.8 ± 10.7 |
| Gamma-glutamyl Transferase (GGT)(U/L) | Enrolled, Did Not Initiate Immunosuppression Withdrawal | Initiated Immunosuppression Withdrawal | Total |
|---|---|---|---|
| Mean | — | 34.2 ± 24.58 | 34.2 ± 24.58 |
6 further baseline measures are reported on the registry.
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National Institute of Allergy and Infectious Diseases (NIAID)