Standard Versus Prolonged-release Tacrolimus Monotherapy After Alemtuzumab Induction in Kidney Transplantation (TAESR)

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

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.

Study Overview

• Status: Completed
• Conditions: Graft Rejection; End-stage Renal Failure
• Intervention / Treatment: Drug: Kidney transplant maintenance immunosuppression; Drug: Tacrolimus (Kidney transplant maintenance immunosuppression)

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.

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W12 0HS
    • West London Renal & Transplant Centre, Hammersmith Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prolonged-Release Tacrolimus; Transplant maintenance immunosuppression with Prolonged-release Tacrolimus monotherapy	Drug: Kidney transplant maintenance immunosuppression; Prolonged-release Tacrolimus 1 to 20mg daily in a single am dose adjusted to trough drug levels 6-9ng/ml; Other Names: Advagraf
Active Comparator: Standard-Release tacrolimus; Transplant maintenance immunosuppression with Standard-release Tacrolimus monotherapy	Drug: Tacrolimus (Kidney transplant maintenance immunosuppression); Standard-release Tacrolimus 1 to 20mg daily in two divided doses to maintain trough drug levels 6-9ng/ml; Other Names: Prograf

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Patient Survival With a Functioning Graft	One year post kidney transplantation

Secondary Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Imperial College Healthcare NHS Trust
• Investigators: Principal Investigator: Adam G McLean, MA DPhil, Imperial College Kidney & Transplant Institute

Publications and helpful links

Helpful Links

• Conference abstract

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2008
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: December 10, 2008
• First Submitted That Met QC Criteria: December 10, 2008
• First Posted (Estimate): December 11, 2008

Study Record Updates

• Last Update Posted (Actual): August 27, 2021
• Last Update Submitted That Met QC Criteria: August 26, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Adherence; Rejection; Quality of life; Kidney transplant
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: ICKTI08TX02; 2008-000889-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No