Clinical trial NCT00807144: Standard Versus Prolonged-release Tacrolimus Monotherapy After Alemtuzumab Induction in Kidney Transplantation
Official title: A Phase-IV Study Comparing Standard Release Tacrolimus (Prograf) vs Prolonged-release Tacrolimus (Advagraf) Monotherapy as Maintenance Immunosuppression After Induction With Alemtuzumab in Kidney Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: End-stage Renal Failure
Graft Rejection
Keywords: Kidney transplant
Rejection
Adherence
Quality of life
Lead sponsor: Imperial College Healthcare NHS Trust
Sponsor class: OTHER
First posted: 2008-12-11
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Patient Survival With a Functioning Graft
timeFrame: One year post kidney transplantation
Secondary outcomes:
measure: Rejection-free Patient Survival With a Functioning Graft
timeFrame: One and two years post kidney transplantation
measure: Patient-reported Quality of Life, and Medication Adherence
timeFrame: 3,6,& 12 months post kidney transplant
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: West London Renal & Transplant Centre, Hammersmith Hospital
Study officials:
affiliation: Imperial College Kidney & Transplant Institute
name: Adam G McLean, MA DPhil
role: PRINCIPAL_INVESTIGATOR
References: