End-stage Renal Failure, Graft Rejection
Conditions
Keywords
Kidney transplant, Rejection, Adherence, Quality of life
Brief summary
The current anti-rejection drug regime for kidney transplant recipients in use at the West London Renal & Transplant Centre (WLRaTC) consists of induction therapy with the very potent monoclonal antibody Campath 1-H (Alemtuzumab) followed by long-term maintenance with the Calcineurin inhibitor Tacrolimus The recent development (and licensing in the UK) of an extended-release, once daily formulation of Tacrolimus holds out the promise of simpler drug regimes for our patients. In the context of our current successful use of Tacrolimus monotherapy maintenance after Campath 1-H induction, the extended-release Tacrolimus formulation will enable us to offer a regime where the only long-term immunosuppressive treatment that most of our patients need will be a single drug, taken once a day. The investigators wish to assess the efficacy of such a regime in a structured comparison with our current protocol.
Detailed description
1. Purpose of Study: The current immunosuppressive regime used as anti-rejection therapy after kidney transplantation in the West London Renal & Transplant Centre at Imperial College Healthcare NHS Trust consists of induction therapy with Campath 1-H(Alemtuzumab) and a 1 week course of steroids followed by maintenance mono-therapy with standard-release (twice daily) Tacrolimus (Prograf). This study is designed to compare the costs and outcomes of this regime with one in which extended-release (once daily) Tacrolimus (Advagraf) is used in place of the standard-release Tacrolimus. 2. Study Type: Phase IV 3. Study Design: Prospective, randomised, controlled, open study. Patients will be randomized 1:1 between the standard and extended-release Tacrolimus arms. Study entry will be stratified by live donor vs deceased donor transplants. The total recruitment target is 100 patients (50 standard release/50 extended release). 4. Study Description: Patients will be randomised to receive either Prograf or Advagraf prior to transplantation. Other than through the taking of extra blood samples at the time of routine clinical visits, participants will receive identical in-patient and out-patient management to patients undergoing kidney transplantation under our standard protocol. Patients in the study will be asked to complete a short Health-Related Quality of Life questionnaire (SF-36) before transplantation and at 1 year post transplant. They will also be asked to complete a Medication Adherence Rating Score at 3, 6, and 12 months post-transplant.
Interventions
Standard-release Tacrolimus 1 to 20mg daily in two divided doses to maintain trough drug levels 6-9ng/ml
DRUGKidney transplant maintenance immunosuppression
Prolonged-release Tacrolimus 1 to 20mg daily in a single am dose adjusted to trough drug levels 6-9ng/ml
Sponsors
Imperial College Healthcare NHS Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Live donor kidney transplant recipients * heart-beating-Deceased donor kidney transplant recipients * Patients suitable for induction therapy with Alemtuzumab
Exclusion criteria
* Recipients of Non-heart-beating deceased donor kidney transplants * Recipients of simultaneous kidney/pancreas transplants * ABO incompatible/desensitized transplant recipients * Positive flow cross-match/desensitized transplant recipients * Patients with heavy prior exposure to myelosuppressive therapy * Patients with previous malignancy * Patients with HIV,Hepatitis-C, or Hepatitis-B infection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Patient Survival With a Functioning Graft | One year post kidney transplantation |
Secondary
| Measure | Time frame |
|---|---|
| Rejection-free Patient Survival With a Functioning Graft | One and two years post kidney transplantation |
| Patient-reported Quality of Life, and Medication Adherence | 3,6,& 12 months post kidney transplant |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Extended Release Tacrolimus Transplant maintenance immunosuppression with Prolonged-release Tacrolimus monotherapy
Kidney transplant maintenance immunosuppression: Prolonged-release Tacrolimus 1 to 20mg daily in a single am dose adjusted to trough drug levels 6-9ng/ml | 52 |
| Standard Release Tacrolimus Transplant maintenance immunosuppression with Standard-release Tacrolimus monotherapy
Tacrolimus (Kidney transplant maintenance immunosuppression): Standard-release Tacrolimus 1 to 20mg daily in two divided doses to maintain trough drug levels 6-9ng/ml | 50 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Standard Release Tacrolimus | Total | Extended Release Tacrolimus |
|---|---|---|---|
| Age, Continuous | 51.5 years STANDARD_DEVIATION 14.04 | 52.3 years STANDARD_DEVIATION 15.1 | 53.1 years STANDARD_DEVIATION 15.8 |
| Race/Ethnicity, Customized Afro Carribean | 6 Participants | 10 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian | 11 Participants | 20 Participants | 9 Participants |
| Race/Ethnicity, Customized Caucasian | 30 Participants | 66 Participants | 36 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 6 Participants | 3 Participants |
| Region of Enrollment United Kingdom | 50 participants | 102 participants | 52 participants |
| Sex: Female, Male Female | 13 Participants | 26 Participants | 13 Participants |
| Sex: Female, Male Male | 37 Participants | 76 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 52 | 2 / 50 |
| other Total, other adverse events | 8 / 52 | 9 / 50 |
| serious Total, serious adverse events | 0 / 52 | 1 / 50 |
Outcome results
Primary
Patient Survival With a Functioning Graft
Time frame: One year post kidney transplantation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Extended Release Tacrolimus | Patient Survival With a Functioning Graft | 92.3 percent of participants |
| Standard Release Tacrolimus | Patient Survival With a Functioning Graft | 96 percent of participants |
p-value: 0.26Log Rank
Secondary
Patient-reported Quality of Life, and Medication Adherence
Time frame: 3,6,& 12 months post kidney transplant
Population: Data not collected
Secondary
Rejection-free Patient Survival With a Functioning Graft
Time frame: One and two years post kidney transplantation
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Extended Release Tacrolimus | Rejection-free Patient Survival With a Functioning Graft | year 1 | 86 percent of participants |
| Extended Release Tacrolimus | Rejection-free Patient Survival With a Functioning Graft | year 2 | 83.4 percent of participants |
| Standard Release Tacrolimus | Rejection-free Patient Survival With a Functioning Graft | year 1 | 84 percent of participants |
| Standard Release Tacrolimus | Rejection-free Patient Survival With a Functioning Graft | year 2 | 80.1 percent of participants |
Comparison: Year 1p-value: 0.48Log Rank
Comparison: Year 2p-value: 0.75Log Rank