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

• Sponsor: Imperial College Healthcare NHS Trust (Other)
• Overall Status: Completed
• CT.gov ID: NCT00807144
• Collaborator: (none)
• Enrollment: 102
• Location: 1
• Arms: 2
• Actual Duration (Months): 39
• Patients Per Site Per Month: 2.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
End-stage Renal Failure; Graft Rejection	Drug: Tacrolimus (Kidney transplant maintenance immunosuppression); Drug: Kidney transplant maintenance immunosuppression	Phase 4

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.

1. Study Type: Phase IV

2. 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).

1. 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 Design

• Study Type: Interventional
• Actual Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• 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
• Actual Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: Mar 1, 2012
• Actual Study Completion Date: Mar 1, 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Patient Survival With a Functioning Graft [One year post kidney transplantation]

Secondary Outcome Measures

1. Rejection-free Patient Survival With a Functioning Graft [One and two years post kidney transplantation]

2. Patient-reported Quality of Life, and Medication Adherence [3,6,& 12 months post kidney transplant]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	West London Renal & Transplant Centre, Hammersmith Hospital	London		United Kingdom	W12 0HS

Sponsors and Collaborators

• Imperial College Healthcare NHS Trust

Investigators

• Principal Investigator: Adam G McLean, MA DPhil, Imperial College Kidney & Transplant Institute

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Conference abstract

Publications

None provided.

• Responsible Party: Imperial College Healthcare NHS Trust
• ClinicalTrials.gov Identifier: NCT00807144
• Other Study ID Numbers: ICKTI08TX02; 2008-000889-22
• First Posted: Dec 11, 2008
• Last Update Posted: Aug 27, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Imperial College Healthcare NHS Trust: Kidney transplant; Rejection; Adherence; Quality of life
• Additional relevant MeSH terms: Kidney Failure, Chronic; Tacrolimus

Study Results

Participant Flow

Arm/Group Title	Extended Release Tacrolimus	Standard Release Tacrolimus
Arm/Group Description	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	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
Period Title: Overall Study
STARTED	52	50
COMPLETED	52	49
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Extended Release Tacrolimus	Standard Release Tacrolimus	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	52	50	102
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.1 (15.8)	51.5 (14.04)	52.3 (15.1)
Sex: Female, Male (Count of Participants)
Female	13 25%	13 26%	26 25.5%
Male	39 75%	37 74%	76 74.5%
Race/Ethnicity, Customized (Count of Participants)
Afro Carribean	4 7.7%	6 12%	10 9.8%
Asian	9 17.3%	11 22%	20 19.6%
Caucasian	36 69.2%	30 60%	66 64.7%
Other	3 5.8%	3 6%	6 5.9%
Region of Enrollment (participants) [Number]
United Kingdom	52 100%	50 100%	102 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Extended Release Tacrolimus	Standard Release Tacrolimus
Arm/Group Description	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	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
Measure Participants	52	50
Number [percent of participants]	92.3 177.5%	96 192%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Extended Release Tacrolimus, Standard Release Tacrolimus
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.26
	Comments
	Method	Log Rank
	Comments

2. Secondary Outcome

Title	Rejection-free Patient Survival With a Functioning Graft
Time Frame	One and two years post kidney transplantation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Extended Release Tacrolimus	Standard Release Tacrolimus
Arm/Group Description	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	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
Measure Participants	52	50
year 1	86 165.4%	84 168%
year 2	83.4 160.4%	80.1 160.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Extended Release Tacrolimus, Standard Release Tacrolimus
	Comments	Year 1
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.48
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Extended Release Tacrolimus, Standard Release Tacrolimus
	Comments	Year 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.75
	Comments
	Method	Log Rank
	Comments

3. Secondary Outcome

Title	Patient-reported Quality of Life, and Medication Adherence
Time Frame	3,6,& 12 months post kidney transplant

Outcome Measure Data

Analysis Population Description

Data not collected

Arm/Group Title	Extended Release Tacrolimus	Standard Release Tacrolimus
Arm/Group Description	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	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
Measure Participants	0	0

Adverse Events

Time Frame	2 years
Arm/Group Title	Extended Release Tacrolimus		Standard Release Tacrolimus
Arm/Group Description	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		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
All Cause Mortality
	Extended Release Tacrolimus		Standard Release Tacrolimus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/52 (7.7%)		2/50 (4%)
Serious Adverse Events
	Extended Release Tacrolimus		Standard Release Tacrolimus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/52 (0%)		1/50 (2%)
Hepatobiliary disorders
Liver failure	0/52 (0%)	0	1/50 (2%)	1
Other (Not Including Serious) Adverse Events
	Extended Release Tacrolimus		Standard Release Tacrolimus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/52 (15.4%)		9/50 (18%)
General disorders
Any rejection symptom	8/52 (15.4%)	8	9/50 (18%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.