Trial Outcomes & Findings for Prospective Study Comparing Brand and Generic Immunosuppression on Transplant Outcomes, Adherence, & Immune Response in Kidney Transplant Recipients (NCT NCT02866682)
NCT ID: NCT02866682
Last Updated: 2023-04-28
Results Overview
The definition of graft failure includes re-transplant and/or death and, in case of kidney transplant, also includes return to dialysis. Acute rejection was defined as biopsy-proven rejection according to Banff 2007 criteria. Please see the following article for details of the Banff '07 classification: https://www.sciencedirect.com/science/article/pii/S1600613522056428?via%3Dihub.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
176 participants
Primary outcome timeframe
1 year post-transplant
Results posted on
2023-04-28
Participant Flow
5 participants withdrew prior to randomization.
Participant milestones
| Measure |
Brand Tacrolimus Only : Prograf
Arm 1 will receive brand tacrolimus for the entire study
Prograf: Brand Drug for the duration of the study.
|
Generic A Only
Arm 2 will receive specific generic tacrolimus for the entire study
Tacrolimus: Generic
|
|---|---|---|
|
Overall Study
STARTED
|
39
|
132
|
|
Overall Study
COMPLETED
|
39
|
120
|
|
Overall Study
NOT COMPLETED
|
0
|
12
|
Reasons for withdrawal
| Measure |
Brand Tacrolimus Only : Prograf
Arm 1 will receive brand tacrolimus for the entire study
Prograf: Brand Drug for the duration of the study.
|
Generic A Only
Arm 2 will receive specific generic tacrolimus for the entire study
Tacrolimus: Generic
|
|---|---|---|
|
Overall Study
Death
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
4
|
|
Overall Study
Tacrolimus Discontinued During Study
|
0
|
6
|
|
Overall Study
Other
|
0
|
1
|
Baseline Characteristics
Prospective Study Comparing Brand and Generic Immunosuppression on Transplant Outcomes, Adherence, & Immune Response in Kidney Transplant Recipients
Baseline characteristics by cohort
| Measure |
Brand Tacrolimus Only : Prograf
n=39 Participants
Arm 1 will receive brand tacrolimus for the entire study
Prograf: Brand Drug for the duration of the study.
|
Generic A Only
n=132 Participants
Arm 2 will receive specific generic tacrolimus for the entire study
Tacrolimus: Generic
|
Total
n=171 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
53.0 years
STANDARD_DEVIATION 12.7 • n=5 Participants
|
52.2 years
STANDARD_DEVIATION 13.1 • n=7 Participants
|
52.5 years
STANDARD_DEVIATION 13.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
58 Participants
n=7 Participants
|
73 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=5 Participants
|
74 Participants
n=7 Participants
|
98 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White, Non-Hispanic
|
9 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
5 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
3 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
12 Participants
n=5 Participants
|
50 Participants
n=7 Participants
|
62 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Multiracial
|
6 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
4 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
39 Participants
n=5 Participants
|
132 Participants
n=7 Participants
|
171 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 1 year post-transplantPopulation: No participants experienced graft rejection or death in the Brand Tacrolimus group. Only 1 participant on the Brand group experienced graft failure. On the other hand, the generic group had 9 participants that experienced rejection, 1 that experienced graft failure, and 1 that experienced death.
The definition of graft failure includes re-transplant and/or death and, in case of kidney transplant, also includes return to dialysis. Acute rejection was defined as biopsy-proven rejection according to Banff 2007 criteria. Please see the following article for details of the Banff '07 classification: https://www.sciencedirect.com/science/article/pii/S1600613522056428?via%3Dihub.
Outcome measures
| Measure |
Brand Tacrolimus Only : Prograf
n=1 Participants
Arm 1 will receive brand tacrolimus for the entire study
Prograf: Brand Drug for the duration of the study.
|
Generic A Only
n=11 Participants
Arm 2 will receive specific generic tacrolimus for the entire study
Tacrolimus: Generic
|
|---|---|---|
|
Time to First Occurrence of Acute Rejection, Failure, Death
Time to first of rejection
|
—
|
57.1 days
Standard Deviation 66.5
|
|
Time to First Occurrence of Acute Rejection, Failure, Death
Time to first graft failure
|
86 days
|
200 days
|
|
Time to First Occurrence of Acute Rejection, Failure, Death
Time to first death
|
—
|
200 days
|
SECONDARY outcome
Timeframe: 1 year post-transplantRejection was defined as biopsy-proven rejection according to Banff 2007 criteria. Please see the following article for details of the Banff '07 classification: https://www.sciencedirect.com/science/article/pii/S1600613522056428?via%3Dihub.
Outcome measures
| Measure |
Brand Tacrolimus Only : Prograf
n=39 Participants
Arm 1 will receive brand tacrolimus for the entire study
Prograf: Brand Drug for the duration of the study.
|
Generic A Only
n=120 Participants
Arm 2 will receive specific generic tacrolimus for the entire study
Tacrolimus: Generic
|
|---|---|---|
|
Number of Participants With Graft Rejection at 1 Year
|
0 Participants
|
9 Participants
|
SECONDARY outcome
Timeframe: 1 year post-transplantGraft failure as determined by return to dialysis, death, or re-transplant
Outcome measures
| Measure |
Brand Tacrolimus Only : Prograf
n=39 Participants
Arm 1 will receive brand tacrolimus for the entire study
Prograf: Brand Drug for the duration of the study.
|
Generic A Only
n=120 Participants
Arm 2 will receive specific generic tacrolimus for the entire study
Tacrolimus: Generic
|
|---|---|---|
|
Number of Participants With Graft Failure at 1 Year
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 1 year post-transplantInfectious episodes are defined as a positive test result for an infection.
Outcome measures
| Measure |
Brand Tacrolimus Only : Prograf
n=39 Participants
Arm 1 will receive brand tacrolimus for the entire study
Prograf: Brand Drug for the duration of the study.
|
Generic A Only
n=120 Participants
Arm 2 will receive specific generic tacrolimus for the entire study
Tacrolimus: Generic
|
|---|---|---|
|
Number of Participants With Infectious Episodes at 1 Year
Cytomegalovirus infection
|
10 participants
|
22 participants
|
|
Number of Participants With Infectious Episodes at 1 Year
BK virus infection
|
3 participants
|
16 participants
|
|
Number of Participants With Infectious Episodes at 1 Year
Other infection
|
15 participants
|
34 participants
|
SECONDARY outcome
Timeframe: 1 year post-transplantMalignancy is defined as physician reported malignancy according to review of participants' medical history.
Outcome measures
| Measure |
Brand Tacrolimus Only : Prograf
n=39 Participants
Arm 1 will receive brand tacrolimus for the entire study
Prograf: Brand Drug for the duration of the study.
|
Generic A Only
n=132 Participants
Arm 2 will receive specific generic tacrolimus for the entire study
Tacrolimus: Generic
|
|---|---|---|
|
Number of Participants With Malignancy at 1 Year
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 1 year post-transplantOutcome measures
| Measure |
Brand Tacrolimus Only : Prograf
n=39 Participants
Arm 1 will receive brand tacrolimus for the entire study
Prograf: Brand Drug for the duration of the study.
|
Generic A Only
n=132 Participants
Arm 2 will receive specific generic tacrolimus for the entire study
Tacrolimus: Generic
|
|---|---|---|
|
Death or Loss-to-follow-up at 1 Year
|
0 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: post-transplantPopulation: Outcome was not collected or measured due to approved changes in protocol amendment
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: post-transplantPopulation: Remaining participants did not have adherence data collected due to appointment cancellations during Covid-19 pandemic
Patient adherence was assessed by their physician with participants marked as "adherent," "non-adherent," or "unknown."
Outcome measures
| Measure |
Brand Tacrolimus Only : Prograf
n=37 Participants
Arm 1 will receive brand tacrolimus for the entire study
Prograf: Brand Drug for the duration of the study.
|
Generic A Only
n=106 Participants
Arm 2 will receive specific generic tacrolimus for the entire study
Tacrolimus: Generic
|
|---|---|---|
|
Number of Participants Who Adhered to Medication Regimen
|
37 Participants
|
105 Participants
|
SECONDARY outcome
Timeframe: post-transplantPopulation: This was not collected due to protocol amendment changes which no longer required this outcome data.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: post-transplantPopulation: Outcome not measured or collected due to approved changes in protocol amendment
Outcome measures
Outcome data not reported
Adverse Events
Brand Tacrolimus Only : Prograf
Serious events: 19 serious events
Other events: 32 other events
Deaths: 0 deaths
Generic A Only
Serious events: 43 serious events
Other events: 105 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Brand Tacrolimus Only : Prograf
n=39 participants at risk
Arm 1 will receive brand tacrolimus for the entire study
Prograf: Brand Drug for the duration of the study.
|
Generic A Only
n=132 participants at risk
Arm 2 will receive specific generic tacrolimus for the entire study
Tacrolimus: Generic
|
|---|---|---|
|
General disorders
Life threatening event associated with an immediate risk of death
|
0.00%
0/39 • 1 Year Post-Transplant
|
0.76%
1/132 • Number of events 1 • 1 Year Post-Transplant
|
|
General disorders
Re-hospitalization
|
33.3%
13/39 • Number of events 30 • 1 Year Post-Transplant
|
31.1%
41/132 • Number of events 98 • 1 Year Post-Transplant
|
|
General disorders
Prolonged hospitalization
|
25.6%
10/39 • Number of events 15 • 1 Year Post-Transplant
|
4.5%
6/132 • Number of events 6 • 1 Year Post-Transplant
|
|
General disorders
Important medical event requiring medical intervention
|
2.6%
1/39 • Number of events 1 • 1 Year Post-Transplant
|
0.76%
1/132 • Number of events 1 • 1 Year Post-Transplant
|
Other adverse events
| Measure |
Brand Tacrolimus Only : Prograf
n=39 participants at risk
Arm 1 will receive brand tacrolimus for the entire study
Prograf: Brand Drug for the duration of the study.
|
Generic A Only
n=132 participants at risk
Arm 2 will receive specific generic tacrolimus for the entire study
Tacrolimus: Generic
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
15.4%
6/39 • 1 Year Post-Transplant
|
10.6%
14/132 • 1 Year Post-Transplant
|
|
Renal and urinary disorders
Acute Kidney Injury
|
23.1%
9/39 • 1 Year Post-Transplant
|
22.7%
30/132 • 1 Year Post-Transplant
|
|
Blood and lymphatic system disorders
Anemia
|
15.4%
6/39 • 1 Year Post-Transplant
|
25.0%
33/132 • 1 Year Post-Transplant
|
|
Gastrointestinal disorders
Constipation
|
12.8%
5/39 • 1 Year Post-Transplant
|
12.9%
17/132 • 1 Year Post-Transplant
|
|
Gastrointestinal disorders
Diarrhea
|
28.2%
11/39 • 1 Year Post-Transplant
|
20.5%
27/132 • 1 Year Post-Transplant
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
10.3%
4/39 • 1 Year Post-Transplant
|
6.8%
9/132 • 1 Year Post-Transplant
|
|
Renal and urinary disorders
Hematuria
|
12.8%
5/39 • 1 Year Post-Transplant
|
7.6%
10/132 • 1 Year Post-Transplant
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
33.3%
13/39 • 1 Year Post-Transplant
|
15.2%
20/132 • 1 Year Post-Transplant
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
5.1%
2/39 • 1 Year Post-Transplant
|
15.9%
21/132 • 1 Year Post-Transplant
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
35.9%
14/39 • 1 Year Post-Transplant
|
31.1%
41/132 • 1 Year Post-Transplant
|
|
Metabolism and nutrition disorders
Hyperphosphatemia
|
17.9%
7/39 • 1 Year Post-Transplant
|
8.3%
11/132 • 1 Year Post-Transplant
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
10.3%
4/39 • 1 Year Post-Transplant
|
10.6%
14/132 • 1 Year Post-Transplant
|
|
Metabolism and nutrition disorders
Hypokalemia
|
10.3%
4/39 • 1 Year Post-Transplant
|
3.8%
5/132 • 1 Year Post-Transplant
|
|
Metabolism and nutrition disorders
Hypomagnesimia
|
35.9%
14/39 • 1 Year Post-Transplant
|
44.7%
59/132 • 1 Year Post-Transplant
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
30.8%
12/39 • 1 Year Post-Transplant
|
38.6%
51/132 • 1 Year Post-Transplant
|
|
Cardiac disorders
Hypotension
|
10.3%
4/39 • 1 Year Post-Transplant
|
7.6%
10/132 • 1 Year Post-Transplant
|
|
Metabolism and nutrition disorders
Impaired Fasting Blood Glucose
|
20.5%
8/39 • 1 Year Post-Transplant
|
4.5%
6/132 • 1 Year Post-Transplant
|
|
Injury, poisoning and procedural complications
Incisional Pain
|
12.8%
5/39 • 1 Year Post-Transplant
|
5.3%
7/132 • 1 Year Post-Transplant
|
|
Infections and infestations
Infection
|
51.3%
20/39 • 1 Year Post-Transplant
|
41.7%
55/132 • 1 Year Post-Transplant
|
|
Immune system disorders
Leukocytosis
|
17.9%
7/39 • 1 Year Post-Transplant
|
11.4%
15/132 • 1 Year Post-Transplant
|
|
Immune system disorders
Leukopenia
|
30.8%
12/39 • 1 Year Post-Transplant
|
31.1%
41/132 • 1 Year Post-Transplant
|
|
Renal and urinary disorders
Lower extremity edema
|
15.4%
6/39 • 1 Year Post-Transplant
|
4.5%
6/132 • 1 Year Post-Transplant
|
|
Metabolism and nutrition disorders
Metabolic Acidosis
|
30.8%
12/39 • 1 Year Post-Transplant
|
22.0%
29/132 • 1 Year Post-Transplant
|
|
Gastrointestinal disorders
Nausea
|
10.3%
4/39 • 1 Year Post-Transplant
|
12.1%
16/132 • 1 Year Post-Transplant
|
|
Immune system disorders
Neutropenia
|
12.8%
5/39 • 1 Year Post-Transplant
|
4.5%
6/132 • 1 Year Post-Transplant
|
|
Injury, poisoning and procedural complications
Post Operative Pain
|
0.00%
0/39 • 1 Year Post-Transplant
|
14.4%
19/132 • 1 Year Post-Transplant
|
|
Renal and urinary disorders
Pyuria
|
23.1%
9/39 • 1 Year Post-Transplant
|
7.6%
10/132 • 1 Year Post-Transplant
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
10.3%
4/39 • 1 Year Post-Transplant
|
6.1%
8/132 • 1 Year Post-Transplant
|
|
Hepatobiliary disorders
Transaminitis
|
23.1%
9/39 • 1 Year Post-Transplant
|
20.5%
27/132 • 1 Year Post-Transplant
|
|
Musculoskeletal and connective tissue disorders
Tremor
|
12.8%
5/39 • 1 Year Post-Transplant
|
18.2%
24/132 • 1 Year Post-Transplant
|
|
Renal and urinary disorders
Abnormal Urinalysis
|
5.1%
2/39 • 1 Year Post-Transplant
|
0.00%
0/132 • 1 Year Post-Transplant
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
2.6%
1/39 • 1 Year Post-Transplant
|
8.3%
11/132 • 1 Year Post-Transplant
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.7%
3/39 • 1 Year Post-Transplant
|
3.8%
5/132 • 1 Year Post-Transplant
|
|
Vascular disorders
Deep Vein Thrombosis
|
5.1%
2/39 • 1 Year Post-Transplant
|
3.0%
4/132 • 1 Year Post-Transplant
|
|
Immune system disorders
de novo DSA
|
7.7%
3/39 • 1 Year Post-Transplant
|
0.76%
1/132 • 1 Year Post-Transplant
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
5.1%
2/39 • 1 Year Post-Transplant
|
5.3%
7/132 • 1 Year Post-Transplant
|
|
General disorders
Edema
|
2.6%
1/39 • 1 Year Post-Transplant
|
5.3%
7/132 • 1 Year Post-Transplant
|
|
General disorders
Fatigue
|
5.1%
2/39 • 1 Year Post-Transplant
|
2.3%
3/132 • 1 Year Post-Transplant
|
|
General disorders
Headache
|
7.7%
3/39 • 1 Year Post-Transplant
|
3.8%
5/132 • 1 Year Post-Transplant
|
|
Cardiac disorders
Hypertension
|
2.6%
1/39 • 1 Year Post-Transplant
|
8.3%
11/132 • 1 Year Post-Transplant
|
|
Renal and urinary disorders
Elevated BUN
|
5.1%
2/39 • 1 Year Post-Transplant
|
0.00%
0/132 • 1 Year Post-Transplant
|
|
Renal and urinary disorders
Kidney Transplant Rejection
|
0.00%
0/39 • 1 Year Post-Transplant
|
6.8%
9/132 • 1 Year Post-Transplant
|
|
Cardiac disorders
Orthostatic Hypotension
|
0.00%
0/39 • 1 Year Post-Transplant
|
6.1%
8/132 • 1 Year Post-Transplant
|
|
Renal and urinary disorders
Proteinuria
|
5.1%
2/39 • 1 Year Post-Transplant
|
0.76%
1/132 • 1 Year Post-Transplant
|
|
General disorders
Pyrexia
|
5.1%
2/39 • 1 Year Post-Transplant
|
6.8%
9/132 • 1 Year Post-Transplant
|
|
Endocrine disorders
Secondary Hyperparathyroidism
|
5.1%
2/39 • 1 Year Post-Transplant
|
0.00%
0/132 • 1 Year Post-Transplant
|
|
Endocrine disorders
Uncontrolled Diabetes
|
5.1%
2/39 • 1 Year Post-Transplant
|
0.76%
1/132 • 1 Year Post-Transplant
|
|
General disorders
Vomiting
|
7.7%
3/39 • 1 Year Post-Transplant
|
3.8%
5/132 • 1 Year Post-Transplant
|
|
General disorders
Weight Gain
|
5.1%
2/39 • 1 Year Post-Transplant
|
5.3%
7/132 • 1 Year Post-Transplant
|
Additional Information
Dr. Suphamai Bunnapradist
University of California, Los Angeles (UCLA)
Phone: 310-794-8516
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place