Trial Outcomes & Findings for Immune Monitoring and CNI Withdrawal in Low Risk Recipients of Kidney Transplantation (NCT NCT01517984)
NCT ID: NCT01517984
Last Updated: 2017-09-11
Results Overview
The investigators were not able to assess this outcome, the effect of the intervention on interstitial fibrosis/tubular atrophy (IF/TA; on a 2-year graft biopsy) due to the study's premature termination by the Data Safety Monitoring Board (DSMB) because of absence of equipoise on the basis of predetermined stopping rules.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
52 participants
Primary outcome timeframe
IF/TA scores on protocol biopsies obtained at 24 months post-randomization will be compared to those obtained at the time of implantation for this measurement.
Results posted on
2017-09-11
Participant Flow
Participant milestones
| Measure |
Enrolled, Not Transplanted
These participants were consented and enrolled into the study, but did receive a living-donor kidney allograft transplant as specified by the protocol.
|
Transplanted, Not Randomized
These participants were enrolled into the study and received a living-donor kidney allograft transplant. Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for up to 8 months and deemed ineligible for randomization or terminated for other reasons.
|
Randomized to Tacrolimus Withdrawal
These participants were enrolled into the study and received a living-donor kidney allograft transplant. Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for 6-8 months then randomized to tacrolimus withdrawal. Following randomization these participants had their dose of tacrolimus withdrawn gradually over three to four months, with complete withdrawal occurring no later than four months. Participants were followed up to 18 months after being randomized.
|
Randomized to Control Group
Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for 6-8 months then randomized to control group, where they continued on the pre-randomization standard care of mycophenolate mofetil, prednisone, and tacrolimus. Participants were followed up to 18 months after being randomized.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
5
|
26
|
14
|
7
|
|
Overall Study
COMPLETED
|
0
|
3
|
10
|
6
|
|
Overall Study
NOT COMPLETED
|
5
|
23
|
4
|
1
|
Reasons for withdrawal
| Measure |
Enrolled, Not Transplanted
These participants were consented and enrolled into the study, but did receive a living-donor kidney allograft transplant as specified by the protocol.
|
Transplanted, Not Randomized
These participants were enrolled into the study and received a living-donor kidney allograft transplant. Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for up to 8 months and deemed ineligible for randomization or terminated for other reasons.
|
Randomized to Tacrolimus Withdrawal
These participants were enrolled into the study and received a living-donor kidney allograft transplant. Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for 6-8 months then randomized to tacrolimus withdrawal. Following randomization these participants had their dose of tacrolimus withdrawn gradually over three to four months, with complete withdrawal occurring no later than four months. Participants were followed up to 18 months after being randomized.
|
Randomized to Control Group
Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for 6-8 months then randomized to control group, where they continued on the pre-randomization standard care of mycophenolate mofetil, prednisone, and tacrolimus. Participants were followed up to 18 months after being randomized.
|
|---|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
8
|
4
|
1
|
|
Overall Study
Screen Failure
|
4
|
0
|
0
|
0
|
|
Overall Study
Ineligible for randomization
|
0
|
14
|
0
|
0
|
Baseline Characteristics
Immune Monitoring and CNI Withdrawal in Low Risk Recipients of Kidney Transplantation
Baseline characteristics by cohort
| Measure |
Transplanted, But Not Randomized
n=26 Participants
These participants were enrolled into the study and received a living-donor kidney allograft transplant. Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for up to 8 months and deemed ineligible for randomization or terminated for other reasons.
|
Randomized to Tacrolimus Withdrawal
n=14 Participants
These participants were enrolled into the study and received a living-donor kidney allograft transplant. Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for 6-8 months then randomized to tacrolimus withdrawal. Following randomization these participants had their dose of tacrolimus withdrawn gradually over three to four months, with complete withdrawal occurring no later than four months. Participants were followed up to 18 months after being randomized.
|
Randomized to Control Group
n=7 Participants
Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for 6-8 months then randomized to control group, where the continued on the pre-randomization standard care of mycophenolate mofetil, prednisone, and tacrolimus. Participants were followed up to 18 months after being randomized.
|
Total
n=47 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
54.8 years
STANDARD_DEVIATION 11.6 • n=5 Participants
|
46.5 years
STANDARD_DEVIATION 14.4 • n=7 Participants
|
44.9 years
STANDARD_DEVIATION 8.5 • n=5 Participants
|
50.9 years
STANDARD_DEVIATION 12.7 • n=4 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
35 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
22 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
39 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
Canada
|
3 participants
n=5 Participants
|
4 participants
n=7 Participants
|
0 participants
n=5 Participants
|
7 participants
n=4 Participants
|
|
Region of Enrollment
United States
|
23 participants
n=5 Participants
|
10 participants
n=7 Participants
|
7 participants
n=5 Participants
|
40 participants
n=4 Participants
|
|
HLA mismatch
|
3.6 Number of HLA marker mismatches
STANDARD_DEVIATION 1.7 • n=5 Participants
|
3.4 Number of HLA marker mismatches
STANDARD_DEVIATION 1.3 • n=7 Participants
|
3.4 Number of HLA marker mismatches
STANDARD_DEVIATION 1.3 • n=5 Participants
|
3.4 Number of HLA marker mismatches
STANDARD_DEVIATION 1.4 • n=4 Participants
|
|
CMV status (donor, recipient)
Donor +, Recipient +
|
8 participants
n=5 Participants
|
5 participants
n=7 Participants
|
0 participants
n=5 Participants
|
13 participants
n=4 Participants
|
|
CMV status (donor, recipient)
Donor +, Recipient -
|
5 participants
n=5 Participants
|
2 participants
n=7 Participants
|
1 participants
n=5 Participants
|
8 participants
n=4 Participants
|
|
CMV status (donor, recipient)
Donor -, Recipient +
|
3 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
7 participants
n=4 Participants
|
|
CMV status (donor, recipient)
Donor -, Recipient -
|
9 participants
n=5 Participants
|
5 participants
n=7 Participants
|
3 participants
n=5 Participants
|
17 participants
n=4 Participants
|
|
CMV status (donor, recipient)
Donor not done, Recipient +
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
1 participants
n=4 Participants
|
|
CMV status (donor, recipient)
Donor missing, Recipient -
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: IF/TA scores on protocol biopsies obtained at 24 months post-randomization will be compared to those obtained at the time of implantation for this measurement.Population: No analyses were performed due to early study closure.
The investigators were not able to assess this outcome, the effect of the intervention on interstitial fibrosis/tubular atrophy (IF/TA; on a 2-year graft biopsy) due to the study's premature termination by the Data Safety Monitoring Board (DSMB) because of absence of equipoise on the basis of predetermined stopping rules.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6 months post-transplantation, 24 months post-transplantationPopulation: Intent-to-treat
Estimated glomerular filtration rate (eGFR) is a test to measure the level of kidney function. In this measure, the effects of tacrolimus withdrawal on long-term kidney function was assessed by comparing absolute 24 month eGFR (18 months post-randomization) and change in eGFR from 6 to 24 months (randomization to 18 months randomization). Lower numbers indicate poorer kidney function
Outcome measures
| Measure |
Randomized to Tacrolimus Withdrawal
n=14 Participants
These participants were enrolled into the study and received a living-donor kidney allograft transplant. Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for 6-8 months then randomized to tacrolimus withdrawal. Following randomization these participants had their dose of tacrolimus withdrawn gradually over three to four months, with complete withdrawal occurring no later than four months. Participants were followed up to 18 months after being randomized.
|
Randomized to Control Group
n=7 Participants
Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for 6-8 months then randomized to control group, where the continued on the pre-randomization standard care of mycophenolate mofetil, prednisone, and tacrolimus. Participants were followed up to 18 months after being randomized.
|
|---|---|---|
|
Estimated GFR Using the Chronic Kidney Disease Epidemiology (CKD-EPI) Equation
24 Month eGFR
|
61.7 mL/min
Standard Deviation 14.8
|
68.6 mL/min
Standard Deviation 24.1
|
|
Estimated GFR Using the Chronic Kidney Disease Epidemiology (CKD-EPI) Equation
6 Month eGFR
|
56.2 mL/min
Standard Deviation 13.9
|
62.3 mL/min
Standard Deviation 15.0
|
|
Estimated GFR Using the Chronic Kidney Disease Epidemiology (CKD-EPI) Equation
Change in eGFR from 6 to 24 months
|
5.5 mL/min
Standard Deviation 12.0
|
6.3 mL/min
Standard Deviation 12.6
|
SECONDARY outcome
Timeframe: 6 to 18 months post-randomizationPopulation: Intent-to-treat
Acute renal allograft rejection is defined as histological reading of borderline or greater determined by the local pathology laboratory. Participants suspected of having a rejection episode on the basis of clinical signs, symptoms, or on the basis of laboratory tests, had a renal ultrasound and underwent a renal transplant biopsy. Any detection of acute cellular rejection or acute humoral rejection resulted in participants in the 'Randomized to Tacrolimus Withdrawal' group to be restarted on tacrolimus and followed per the reduced follow-up schedule of events.
Outcome measures
| Measure |
Randomized to Tacrolimus Withdrawal
n=14 Participants
These participants were enrolled into the study and received a living-donor kidney allograft transplant. Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for 6-8 months then randomized to tacrolimus withdrawal. Following randomization these participants had their dose of tacrolimus withdrawn gradually over three to four months, with complete withdrawal occurring no later than four months. Participants were followed up to 18 months after being randomized.
|
Randomized to Control Group
n=7 Participants
Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for 6-8 months then randomized to control group, where the continued on the pre-randomization standard care of mycophenolate mofetil, prednisone, and tacrolimus. Participants were followed up to 18 months after being randomized.
|
|---|---|---|
|
Incidence of Acute Rejection
|
6 participants
|
0 participants
|
SECONDARY outcome
Timeframe: 6 to 18 months post-randomizationPopulation: Intent-to-treat
Allograft survival is defined as participants who did not need to be re-transplanted or placed on dialysis due to the failure of their allograft transplantation during the course of this study.
Outcome measures
| Measure |
Randomized to Tacrolimus Withdrawal
n=14 Participants
These participants were enrolled into the study and received a living-donor kidney allograft transplant. Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for 6-8 months then randomized to tacrolimus withdrawal. Following randomization these participants had their dose of tacrolimus withdrawn gradually over three to four months, with complete withdrawal occurring no later than four months. Participants were followed up to 18 months after being randomized.
|
Randomized to Control Group
n=7 Participants
Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for 6-8 months then randomized to control group, where the continued on the pre-randomization standard care of mycophenolate mofetil, prednisone, and tacrolimus. Participants were followed up to 18 months after being randomized.
|
|---|---|---|
|
Allograft Survival Rate
|
14 participants
|
7 participants
|
SECONDARY outcome
Timeframe: 6 to 18 months post-transplantationPopulation: Intent-to-treat
Number of participants who did not die within the course of this study.
Outcome measures
| Measure |
Randomized to Tacrolimus Withdrawal
n=14 Participants
These participants were enrolled into the study and received a living-donor kidney allograft transplant. Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for 6-8 months then randomized to tacrolimus withdrawal. Following randomization these participants had their dose of tacrolimus withdrawn gradually over three to four months, with complete withdrawal occurring no later than four months. Participants were followed up to 18 months after being randomized.
|
Randomized to Control Group
n=7 Participants
Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for 6-8 months then randomized to control group, where the continued on the pre-randomization standard care of mycophenolate mofetil, prednisone, and tacrolimus. Participants were followed up to 18 months after being randomized.
|
|---|---|---|
|
Participant Survival Rate
|
14 participants
|
7 participants
|
SECONDARY outcome
Timeframe: 6 to 18 months post-randomizationPopulation: Intent-to-treat
Donor specific antibodies are antibodies that are directed against antigens expressed on donor organs. These antibodies can result in an immune attack on the transplanted organ, increasing risk of graft loss and/or rejection.
Outcome measures
| Measure |
Randomized to Tacrolimus Withdrawal
n=14 Participants
These participants were enrolled into the study and received a living-donor kidney allograft transplant. Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for 6-8 months then randomized to tacrolimus withdrawal. Following randomization these participants had their dose of tacrolimus withdrawn gradually over three to four months, with complete withdrawal occurring no later than four months. Participants were followed up to 18 months after being randomized.
|
Randomized to Control Group
n=7 Participants
Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for 6-8 months then randomized to control group, where the continued on the pre-randomization standard care of mycophenolate mofetil, prednisone, and tacrolimus. Participants were followed up to 18 months after being randomized.
|
|---|---|---|
|
Percentage of Participants With New Donor Specific Antibodies (DSAs)
|
36 percentage of participants
|
14 percentage of participants
|
SECONDARY outcome
Timeframe: 6 to 18 months post-randomizationPopulation: No analyses were performed due to early study closure.
This endpoint was unable to be analyzed because the study was terminated early after stopping rules were met.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 18 months post-randomizationPopulation: Intent-to-treat
Participants in the 'Randomized to Tacrolimus Withdrawal' group were considered fully withdrawn once they no longer received any doses of tacrolimus. Participants met this endpoint if they did not resume taking tacrolimus as of 18 months post randomization with stable allograft function and without rejection of donor-specific antibodies.
Outcome measures
| Measure |
Randomized to Tacrolimus Withdrawal
n=14 Participants
These participants were enrolled into the study and received a living-donor kidney allograft transplant. Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for 6-8 months then randomized to tacrolimus withdrawal. Following randomization these participants had their dose of tacrolimus withdrawn gradually over three to four months, with complete withdrawal occurring no later than four months. Participants were followed up to 18 months after being randomized.
|
Randomized to Control Group
Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for 6-8 months then randomized to control group, where the continued on the pre-randomization standard care of mycophenolate mofetil, prednisone, and tacrolimus. Participants were followed up to 18 months after being randomized.
|
|---|---|---|
|
Percentage of Participants in the Experimental Arm Off Tacrolimus
|
43 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: 6 to 18 months post-transplantPopulation: No analyses were performed due to early study closure.
This endpoint was unable to be analyzed because the study was terminated early after stopping rules were met.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6 months post-transplantation to 18 months post-randomizationPopulation: No analyses were performed due to early study closure.
This endpoint was unable to be analyzed because the study was terminated early after stopping rules were met.
Outcome measures
Outcome data not reported
Adverse Events
Transplanted, But Not Randomized
Serious events: 2 serious events
Other events: 4 other events
Deaths: 0 deaths
Randomized to Tacrolimus Withdrawal
Serious events: 4 serious events
Other events: 5 other events
Deaths: 0 deaths
Randomized to Control Group
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Transplanted, But Not Randomized
n=26 participants at risk
These participants were enrolled into the study and received a living-donor kidney allograft transplant. Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for up to 8 months and deemed ineligible for randomization or terminated for other reasons.
|
Randomized to Tacrolimus Withdrawal
n=14 participants at risk
These participants were enrolled into the study and received a living-donor kidney allograft transplant. Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for 6-8 months then randomized to tacrolimus withdrawal. Following randomization these participants had their dose of tacrolimus withdrawn gradually over three to four months, with complete withdrawal occurring no later than four months. Participants were followed up to 18 months after being randomized.
|
Randomized to Control Group
n=7 participants at risk
Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for 6-8 months then randomized to control group, where they continued on the pre-randomization standard care of mycophenolate mofetil, prednisone, and tacrolimus. Participants were followed up to 18 months after being randomized.
|
|---|---|---|---|
|
Immune system disorders
Transplant rejection
|
3.8%
1/26 • Number of events 1 • Transplantation through end of study (up to 24 months)
|
14.3%
2/14 • Number of events 2 • Transplantation through end of study (up to 24 months)
|
0.00%
0/7 • Transplantation through end of study (up to 24 months)
|
|
Infections and infestations
Cellulitis
|
3.8%
1/26 • Number of events 1 • Transplantation through end of study (up to 24 months)
|
0.00%
0/14 • Transplantation through end of study (up to 24 months)
|
0.00%
0/7 • Transplantation through end of study (up to 24 months)
|
|
Infections and infestations
Pneumonia legionella
|
3.8%
1/26 • Number of events 1 • Transplantation through end of study (up to 24 months)
|
0.00%
0/14 • Transplantation through end of study (up to 24 months)
|
0.00%
0/7 • Transplantation through end of study (up to 24 months)
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/26 • Transplantation through end of study (up to 24 months)
|
7.1%
1/14 • Number of events 1 • Transplantation through end of study (up to 24 months)
|
0.00%
0/7 • Transplantation through end of study (up to 24 months)
|
|
Infections and infestations
Staphylococcal infection
|
0.00%
0/26 • Transplantation through end of study (up to 24 months)
|
7.1%
1/14 • Number of events 1 • Transplantation through end of study (up to 24 months)
|
0.00%
0/7 • Transplantation through end of study (up to 24 months)
|
|
Injury, poisoning and procedural complications
Post procedural haematoma
|
0.00%
0/26 • Transplantation through end of study (up to 24 months)
|
7.1%
1/14 • Number of events 1 • Transplantation through end of study (up to 24 months)
|
0.00%
0/7 • Transplantation through end of study (up to 24 months)
|
Other adverse events
| Measure |
Transplanted, But Not Randomized
n=26 participants at risk
These participants were enrolled into the study and received a living-donor kidney allograft transplant. Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for up to 8 months and deemed ineligible for randomization or terminated for other reasons.
|
Randomized to Tacrolimus Withdrawal
n=14 participants at risk
These participants were enrolled into the study and received a living-donor kidney allograft transplant. Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for 6-8 months then randomized to tacrolimus withdrawal. Following randomization these participants had their dose of tacrolimus withdrawn gradually over three to four months, with complete withdrawal occurring no later than four months. Participants were followed up to 18 months after being randomized.
|
Randomized to Control Group
n=7 participants at risk
Participants were given an induction therapy with rabbit antithymocyte globulin (1.5-2.0 mg/kg daily for 5 days) and treated with a regimen of mycophenolate mofetil (target dose of 1000 mg twice daily), prednisone (no less than 5 mg/day or 10 mg every other day) and tacrolimus (0.1 mg/kg twice daily, adjusted to target trough levels of 8-12 ng/ml in first 3 months post-transplant, 5-8 ng/ml thereafter). Participants were followed for 6-8 months then randomized to control group, where they continued on the pre-randomization standard care of mycophenolate mofetil, prednisone, and tacrolimus. Participants were followed up to 18 months after being randomized.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Leukopenia
|
3.8%
1/26 • Number of events 1 • Transplantation through end of study (up to 24 months)
|
14.3%
2/14 • Number of events 2 • Transplantation through end of study (up to 24 months)
|
0.00%
0/7 • Transplantation through end of study (up to 24 months)
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/26 • Transplantation through end of study (up to 24 months)
|
0.00%
0/14 • Transplantation through end of study (up to 24 months)
|
14.3%
1/7 • Number of events 1 • Transplantation through end of study (up to 24 months)
|
|
General disorders
Hernia obstructive
|
3.8%
1/26 • Number of events 1 • Transplantation through end of study (up to 24 months)
|
0.00%
0/14 • Transplantation through end of study (up to 24 months)
|
0.00%
0/7 • Transplantation through end of study (up to 24 months)
|
|
Immune system disorders
Transplant rejection
|
0.00%
0/26 • Transplantation through end of study (up to 24 months)
|
7.1%
1/14 • Number of events 1 • Transplantation through end of study (up to 24 months)
|
0.00%
0/7 • Transplantation through end of study (up to 24 months)
|
|
Infections and infestations
BK virus infection
|
0.00%
0/26 • Transplantation through end of study (up to 24 months)
|
7.1%
1/14 • Number of events 1 • Transplantation through end of study (up to 24 months)
|
0.00%
0/7 • Transplantation through end of study (up to 24 months)
|
|
Infections and infestations
Cytomegalovirus infection
|
0.00%
0/26 • Transplantation through end of study (up to 24 months)
|
7.1%
1/14 • Number of events 1 • Transplantation through end of study (up to 24 months)
|
14.3%
1/7 • Number of events 1 • Transplantation through end of study (up to 24 months)
|
|
Infections and infestations
Influenza
|
3.8%
1/26 • Number of events 1 • Transplantation through end of study (up to 24 months)
|
0.00%
0/14 • Transplantation through end of study (up to 24 months)
|
0.00%
0/7 • Transplantation through end of study (up to 24 months)
|
|
Metabolism and nutrition disorders
Glucose tolerance impaired
|
3.8%
1/26 • Number of events 1 • Transplantation through end of study (up to 24 months)
|
0.00%
0/14 • Transplantation through end of study (up to 24 months)
|
0.00%
0/7 • Transplantation through end of study (up to 24 months)
|
|
Musculoskeletal and connective tissue disorders
Osteopenia
|
0.00%
0/26 • Transplantation through end of study (up to 24 months)
|
21.4%
3/14 • Number of events 3 • Transplantation through end of study (up to 24 months)
|
0.00%
0/7 • Transplantation through end of study (up to 24 months)
|
|
Musculoskeletal and connective tissue disorders
Osteoporosis
|
3.8%
1/26 • Number of events 1 • Transplantation through end of study (up to 24 months)
|
0.00%
0/14 • Transplantation through end of study (up to 24 months)
|
0.00%
0/7 • Transplantation through end of study (up to 24 months)
|
|
Renal and urinary disorders
Haematuria
|
3.8%
1/26 • Number of events 1 • Transplantation through end of study (up to 24 months)
|
0.00%
0/14 • Transplantation through end of study (up to 24 months)
|
0.00%
0/7 • Transplantation through end of study (up to 24 months)
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/26 • Transplantation through end of study (up to 24 months)
|
7.1%
1/14 • Number of events 1 • Transplantation through end of study (up to 24 months)
|
0.00%
0/7 • Transplantation through end of study (up to 24 months)
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/26 • Transplantation through end of study (up to 24 months)
|
0.00%
0/14 • Transplantation through end of study (up to 24 months)
|
14.3%
1/7 • Number of events 1 • Transplantation through end of study (up to 24 months)
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
3.8%
1/26 • Number of events 1 • Transplantation through end of study (up to 24 months)
|
0.00%
0/14 • Transplantation through end of study (up to 24 months)
|
0.00%
0/7 • Transplantation through end of study (up to 24 months)
|
Additional Information
Director, Clinical Research Operations Program
DAIT/NIAID
Phone: 301-594-7669
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place