AGe-adapted Benefits of Envarsus Versus Twice-daily Tacrolimus ImmunosuppressioN druGs After Kidney Transplantation (AGEING)

December 28, 2016 updated by: Adnan Sharif, University Hospital Birmingham NHS Foundation Trust

AGe-adapted Benefits of Envarsus Versus Twice-daily Tacrolimus ImmunosuppressioN druGs After Kidney Transplantation (AGEING) - a Feasibility Study

The proportion of elderly patients with end-stage kidney disease undergoing renal replacement therapy (RRT) is steadily increasing. Although kidney transplantation remains the optimal RRT of choice, it is clear that older adults have a differential risk versus benefit profile after kidney transplantation compared to younger adults. No age-adapted immunosuppression for older adults has been shown to improve kidney allograft outcomes but recent sub-analyses of clinical trial data has hinted at improved outcomes for older kidney transplant patients receiving Envarsus versus standard twice-daily tacrolimus formulations. This feasibility study will investigate this effect to see whether a full scale randomised controlled trial is warranted and to provide information regarding study feasibility.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The proportion of elderly patients with end-stage kidney disease undergoing renal replacement therapy (RRT) is steadily increasing. National registry data consistently shows a trend towards increasing median ages for patients both starting dialysis and awaiting kidney transplantation on deceased-donor waiting lists (www.renalreg.org). For example, in the United Kingdom, national audit data from the UK Renal Registry demonstrates that the median age for all incident patients commencing RRT was 64.5 years (www.renalreg.org). Among the prevalent RRT population, the percentage of patients aged greater than 70 years has increased from 19.2% (in 2000) to 25.0% (in 2013) in the last registry report (www.renalreg.org). Focusing on data from the UK Transplant Registry, 28% of transplant recipients receiving a deceased-donor kidney allograft in the last year were aged 60 and over (7% were aged 70 and over), while 32% of the active kidney transplant waiting list is aged 60 and over (9% aged 70 and over) (http://www.odt.nhs.uk/uk-transplant-registry/). With chronic kidney disease increasingly recognized as a public health epidemic, the long-term prospects are of an increasingly elderly component to our end-stage kidney disease population.

Kidney transplantation is the gold standard method of RRT due to superior mortality, quality of life and cost effectiveness versus dialysis. It is therefore concerning that transplantation is an infrequent RRT choice for older adults and the number of older adults aged 70 and over who are listed for a kidney transplant is <10%. The Renal Association states; "age is not a contra-indication for transplantation but age related co-morbidity is an important limiting factor", but clearly the risk versus benefit ratio remains unclear for clinicians because mortality risk is higher for older versus younger kidney transplant recipients. However, improved mortality is observed with kidney transplantation versus wait-listed dialysis patients across all age groups, and specifically among older adults aged 70 and above in US studies, and therefore Investigators should consider kidney transplantation for this increasing large cohort. The risk of immunosuppression-related complications increases with age and therefore age-adapted immunosuppression should be considered to balance efficacy versus complications. However, no targeted age-adapted immunosuppression clinical trials have been conducted in kidney transplantation and this remains a major gap in the literature.

Sub-analyses of recently published work showed clinically relevant advantages of Envarsus versus twice-daily tacrolimus for prevention of treatment failure after 2-years among patients aged 65 and over (age ≥65 yrs; -25.89% (-45.11%, 0.36%), p=0.067) (Rostaing et al, AJKD 2016; Budde et al, AJT 2014). However, small numbers render the effect of borderline statistical significance

As one of the largest growing demographics, it is imperative to design a targeted clinical trial to ascertain if Envarsus has clinical benefits above and beyond twice-daily tacrolimus in older kidney transplant recipients. Before that is possible, investigators must investigate two things in preparation for a definitive study; 1) investigators must confirm reproducibility of this trend among older kidney transplant recipients in a separate cohort to determine effect size and power calculations, and 2) identify possible mechanistic, biological and/or pharmacogenomic rationale to understand any effect. This feasibility study will be the first contemporary randomised controlled trial in kidney transplantation looking at a modified age-adapted immunosuppression protocol specifically for older adults, attempting to determine whether the above results can be recreated and probed in greater detail. As one of the most topical questions in the field of transplantation, the results of this feasibility study would advise on the merits of undertaking a more definitive study which would almost certainly be one of the most eagerly awaited studies by global transplant clinicians.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

60 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • kidney alone transplant, age ≥60, known sensitivity to tacrolimus

Exclusion Criteria:

  • contra-indication to transplantation, multi-organ transplant, aged <60

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Envarsus
Basiliximab induction with maintenance therapy of Envarsus, mycophenolate mofetil and corticosteroids. Envarsus constitutes the experimental component of immunosuppression in older kidney transplant recipients.
Drug: ENVARSUS
Envarsus is a once-a-day oral formulation of tacrolimus.
ACTIVE_COMPARATOR: Standard twice daily tacrolimus
Basiliximab induction with maintenance therapy of standard tacrolimus, mycophenolate mofetil and corticosteroids. Standard tacrolimus constitutes the control component of immunosuppression in older kidney transplant recipients.
Drug: Standard twice daily tacrolimus
Standard tacrolimus will include twice-daily formulations that are currently available.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Recruitment rates
Time Frame: 6-months
6-months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Treatment failure (composite endpoint of mortality, graft survival, rejection, loss to follow up)
Time Frame: 6-months
6-months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital Birmingham NHS Foundation Trust

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Adnan Sharif, MD, Consultant Nephrologist

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2017

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2019

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 30, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 28, 2016

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 29, 2016

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 29, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 28, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AGEING

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Kidney Transplant Failure and Rejection

Clinical Trials on ENVARSUS

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings