Trial Outcomes & Findings for Thymoglobulin Induction Therapy With Minimal Immunosuppression and Evaluation of Allograft Status (NCT NCT00731874)
NCT ID: NCT00731874
Last Updated: 2019-06-12
Results Overview
Recruitment status
TERMINATED
Study phase
PHASE4
Target enrollment
34 participants
Primary outcome timeframe
15 months post-transplant
Results posted on
2019-06-12
Participant Flow
34 subjects consented for the study; 11 were enrolled but not randomized due to the following: withdrew consent/refused transplant biopsy (n=4); donor specific antibody detected during screening (n=3); excluded by findings of kidney transplant biopsy (n=2); fluctuation in renal function (n=1); study terminated prior to randomization (n=1).
Participant milestones
| Measure |
Arm 1 (Target Tacrolimus 6 to 8 ng/mL)
Target tacrolimus trough concentration of 6 to 8 ng/mL
Tacrolimus: Dosed to achieve target trough concentrations.
|
Arm 2 (Target Tacrolimus 3 to 5 ng/mL)
Target tacrolimus trough concentration of 3 to 5 ng/mL
Tacrolimus: Dosed to achieve target trough concentrations.
|
|---|---|---|
|
Overall Study
STARTED
|
10
|
13
|
|
Overall Study
COMPLETED
|
10
|
13
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Thymoglobulin Induction Therapy With Minimal Immunosuppression and Evaluation of Allograft Status
Baseline characteristics by cohort
| Measure |
Arm 1 (Target Tacrolimus 6 to 8 ng/mL)
n=10 Participants
Target tacrolimus trough concentration of 6 to 8 ng/mL
Tacrolimus: Dosed to achieve target trough concentrations.
|
Arm 2 (Target Tacrolimus 3 to 5 ng/mL)
n=13 Participants
Target tacrolimus trough concentration of 3 to 5 ng/mL
Tacrolimus: Dosed to achieve target trough concentrations.
|
Total
n=23 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
10 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
21 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Age, Continuous
|
48.4 years
STANDARD_DEVIATION 11.3 • n=93 Participants
|
56.1 years
STANDARD_DEVIATION 10.2 • n=4 Participants
|
52.7 years
STANDARD_DEVIATION 11.1 • n=27 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
17 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=93 Participants
|
13 participants
n=4 Participants
|
23 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: 15 months post-transplantOutcome measures
| Measure |
Arm 1 (Target Tacrolimus 6 to 8 ng/mL)
n=10 Participants
Target tacrolimus trough concentration of 6 to 8 ng/mL
Tacrolimus: Dosed to achieve target trough concentrations.
|
Arm 2 (Target Tacrolimus 3 to 5 ng/mL)
n=13 Participants
Target tacrolimus trough concentration of 3 to 5 ng/mL
Tacrolimus: Dosed to achieve target trough concentrations.
|
|---|---|---|
|
Number of Participants With Biopsy-confirmed Acute Rejection and/or Progression of Histologically Proven Chronic Allograft Nephropathy at 15 Months After Transplantation.
|
0 participants
|
1 participants
|
SECONDARY outcome
Timeframe: 36 months post-transplantOutcome measures
| Measure |
Arm 1 (Target Tacrolimus 6 to 8 ng/mL)
n=10 Participants
Target tacrolimus trough concentration of 6 to 8 ng/mL
Tacrolimus: Dosed to achieve target trough concentrations.
|
Arm 2 (Target Tacrolimus 3 to 5 ng/mL)
n=13 Participants
Target tacrolimus trough concentration of 3 to 5 ng/mL
Tacrolimus: Dosed to achieve target trough concentrations.
|
|---|---|---|
|
Patient Survival
|
10 Participants
|
13 Participants
|
SECONDARY outcome
Timeframe: 36 months post-transplantPopulation: Data are not included for one subject because one subject was lost to follow-up.
Outcome measures
| Measure |
Arm 1 (Target Tacrolimus 6 to 8 ng/mL)
n=10 Participants
Target tacrolimus trough concentration of 6 to 8 ng/mL
Tacrolimus: Dosed to achieve target trough concentrations.
|
Arm 2 (Target Tacrolimus 3 to 5 ng/mL)
n=12 Participants
Target tacrolimus trough concentration of 3 to 5 ng/mL
Tacrolimus: Dosed to achieve target trough concentrations.
|
|---|---|---|
|
Graft Survival
|
10 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: 36 months post-transplantCompared to the baseline biopsy performed at the time of study entry at 3 months, was there new development (incidence) or progression (severity) of interstitial fibrosis/tubular atrophy (formerly called chronic allograft nephropathy) in the biopsy performed at 36 months.
Outcome measures
| Measure |
Arm 1 (Target Tacrolimus 6 to 8 ng/mL)
n=10 Participants
Target tacrolimus trough concentration of 6 to 8 ng/mL
Tacrolimus: Dosed to achieve target trough concentrations.
|
Arm 2 (Target Tacrolimus 3 to 5 ng/mL)
n=13 Participants
Target tacrolimus trough concentration of 3 to 5 ng/mL
Tacrolimus: Dosed to achieve target trough concentrations.
|
|---|---|---|
|
Change in Incidence and Severity of Interstitial Fibrosis/Tubular Atrophy (IF/TA) From the Baseline 3-month Biopsy to the 36-month Biopsy
Progression of IFTA
|
2 Participants
|
5 Participants
|
|
Change in Incidence and Severity of Interstitial Fibrosis/Tubular Atrophy (IF/TA) From the Baseline 3-month Biopsy to the 36-month Biopsy
New IFTA
|
2 Participants
|
1 Participants
|
|
Change in Incidence and Severity of Interstitial Fibrosis/Tubular Atrophy (IF/TA) From the Baseline 3-month Biopsy to the 36-month Biopsy
Stable Biopsy
|
4 Participants
|
6 Participants
|
|
Change in Incidence and Severity of Interstitial Fibrosis/Tubular Atrophy (IF/TA) From the Baseline 3-month Biopsy to the 36-month Biopsy
No Data
|
2 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 36 months post-transplantPopulation: Data are not included for one subject because one subject was lost to follow-up.
Outcome measures
| Measure |
Arm 1 (Target Tacrolimus 6 to 8 ng/mL)
n=10 Participants
Target tacrolimus trough concentration of 6 to 8 ng/mL
Tacrolimus: Dosed to achieve target trough concentrations.
|
Arm 2 (Target Tacrolimus 3 to 5 ng/mL)
n=12 Participants
Target tacrolimus trough concentration of 3 to 5 ng/mL
Tacrolimus: Dosed to achieve target trough concentrations.
|
|---|---|---|
|
Renal Function (Estimated Glomerular Filtration Rate)
eGFR>60
|
2 Participants
|
5 Participants
|
|
Renal Function (Estimated Glomerular Filtration Rate)
eGFR 50-59
|
4 Participants
|
3 Participants
|
|
Renal Function (Estimated Glomerular Filtration Rate)
eGFR 40-49
|
2 Participants
|
1 Participants
|
|
Renal Function (Estimated Glomerular Filtration Rate)
eGFR 30-39
|
1 Participants
|
2 Participants
|
|
Renal Function (Estimated Glomerular Filtration Rate)
eGFR 20-29
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 36 months post-transplantPercent of subjects who developed new donor specific antibody (mean fluorescence intensity \> 3,000) after enrollment, within 36 months of transplant
Outcome measures
| Measure |
Arm 1 (Target Tacrolimus 6 to 8 ng/mL)
n=10 Participants
Target tacrolimus trough concentration of 6 to 8 ng/mL
Tacrolimus: Dosed to achieve target trough concentrations.
|
Arm 2 (Target Tacrolimus 3 to 5 ng/mL)
n=13 Participants
Target tacrolimus trough concentration of 3 to 5 ng/mL
Tacrolimus: Dosed to achieve target trough concentrations.
|
|---|---|---|
|
Development of Donor Specific Antibody (DSA)
|
0 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: 36 months post-transplantIncidence of biopsy-proven acute rejection
Outcome measures
| Measure |
Arm 1 (Target Tacrolimus 6 to 8 ng/mL)
n=10 Participants
Target tacrolimus trough concentration of 6 to 8 ng/mL
Tacrolimus: Dosed to achieve target trough concentrations.
|
Arm 2 (Target Tacrolimus 3 to 5 ng/mL)
n=13 Participants
Target tacrolimus trough concentration of 3 to 5 ng/mL
Tacrolimus: Dosed to achieve target trough concentrations.
|
|---|---|---|
|
Incidence of Acute Rejection
|
0 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: 36 months post-transplantPopulation: Data reported only for those subjects who developed acute rejection during the study, per protocol. Three of the 5 subjects in Arm 2 with rejection were treated with rabbit anti-thymocyte globulin.
The severity of acute rejection may be assessed by the Banff criteria. The Banff Classification of Allograft Pathology is an international consensus classification for the reporting of renal allograft biopsies, and provides critical information enabling the diagnosis and grading of pathologic changes, can help to predict response to treatment, and can help to determine the long-term prognosis of the organ. Anti-lymphocyte agents (specifically rabbit anti-thymocyte globulin) are used to treat more severe cases of acute rejection, and thus may serve as a surrogate marker of severity.
Outcome measures
| Measure |
Arm 1 (Target Tacrolimus 6 to 8 ng/mL)
Target tacrolimus trough concentration of 6 to 8 ng/mL
Tacrolimus: Dosed to achieve target trough concentrations.
|
Arm 2 (Target Tacrolimus 3 to 5 ng/mL)
n=5 Participants
Target tacrolimus trough concentration of 3 to 5 ng/mL
Tacrolimus: Dosed to achieve target trough concentrations.
|
|---|---|---|
|
Severity of Acute Rejection (by Banff Criteria and Need for Anti-lymphocyte Agents to Treat Acute Rejection)
Mixed T cell and Antibody Mediated Rejection
|
0 Participants
|
3 Participants
|
|
Severity of Acute Rejection (by Banff Criteria and Need for Anti-lymphocyte Agents to Treat Acute Rejection)
Antibody Mediated Rejection
|
0 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: 36 months post-transplantOutcome measures
| Measure |
Arm 1 (Target Tacrolimus 6 to 8 ng/mL)
n=10 Participants
Target tacrolimus trough concentration of 6 to 8 ng/mL
Tacrolimus: Dosed to achieve target trough concentrations.
|
Arm 2 (Target Tacrolimus 3 to 5 ng/mL)
n=13 Participants
Target tacrolimus trough concentration of 3 to 5 ng/mL
Tacrolimus: Dosed to achieve target trough concentrations.
|
|---|---|---|
|
Incidence of Opportunistic Infection
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 36 months post-transplantPopulation: Only subjects who did not have a diagnosis of diabetes mellitus at transplant are included, per protocol.
Outcome measures
| Measure |
Arm 1 (Target Tacrolimus 6 to 8 ng/mL)
n=8 Participants
Target tacrolimus trough concentration of 6 to 8 ng/mL
Tacrolimus: Dosed to achieve target trough concentrations.
|
Arm 2 (Target Tacrolimus 3 to 5 ng/mL)
n=9 Participants
Target tacrolimus trough concentration of 3 to 5 ng/mL
Tacrolimus: Dosed to achieve target trough concentrations.
|
|---|---|---|
|
Development of New Onset Diabetes Mellitus
|
1 Participants
|
2 Participants
|
Adverse Events
Arm 1 (Target Tacrolimus 6 to 8 ng/mL)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Arm 2 (Target Tacrolimus 3 to 5 ng/mL)
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Arm 1 (Target Tacrolimus 6 to 8 ng/mL)
n=10 participants at risk
Target tacrolimus trough concentration of 6 to 8 ng/mL
Tacrolimus: Dosed to achieve target trough concentrations.
|
Arm 2 (Target Tacrolimus 3 to 5 ng/mL)
n=13 participants at risk
Target tacrolimus trough concentration of 3 to 5 ng/mL
Tacrolimus: Dosed to achieve target trough concentrations.
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Pain, Hip
|
0.00%
0/10
|
7.7%
1/13 • Number of events 1
|
|
Cardiac disorders
Chest Pain
|
0.00%
0/10
|
7.7%
1/13 • Number of events 1
|
|
Infections and infestations
Cytomegalovirus viremia
|
0.00%
0/10
|
7.7%
1/13 • Number of events 1
|
|
Renal and urinary disorders
Antibody-mediated rejection
|
0.00%
0/10
|
38.5%
5/13 • Number of events 5
|
|
Skin and subcutaneous tissue disorders
Non-melanoma skin cancer
|
10.0%
1/10 • Number of events 1
|
0.00%
0/13
|
|
Reproductive system and breast disorders
Menorrhagia
|
10.0%
1/10 • Number of events 1
|
0.00%
0/13
|
|
Infections and infestations
Strongyloides infection
|
10.0%
1/10 • Number of events 1
|
0.00%
0/13
|
|
Reproductive system and breast disorders
Endometritis
|
10.0%
1/10 • Number of events 1
|
0.00%
0/13
|
|
Renal and urinary disorders
Urinary Tract Infection
|
10.0%
1/10 • Number of events 1
|
0.00%
0/13
|
Additional Information
Dr. Meredith J Aull
Weill Cornell Medical College/Division of Transplant Surgery
Phone: (212) 746-0727
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place