- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01769924
A Prospective UK Multicentre Study of Kidney Donors (EARNEST)
Effect of A Reduction in Glomerular Filtration Rate After Nephrectomy on Arterial Stiffness (EARNEST)
Study Overview
Detailed Description
HYPOTHESIS
In living kidney donors, reduction in GFR post-nephrectomy results in:
- A pressure-independent increase in aortic stiffness (aPWV)
- An increase in peripheral and central blood pressure
EXPERIMENTAL DETAILS AND DESIGN OF PROPOSED INVESTIGATION We propose a prospective, longitudinal parallel group study of 200 kidney donors and 200 controls to be recruited over two years and followed up over one year.
Subjects: The only inclusion criterion is that subjects will be scheduled for nephrectomy for the purpose of kidney donation. Subjects will be recruited from centres, chosen because of their high numbers of live donor transplants and strength in vascular research.
Controls: We will recruit a carefully matched series of control patients from the same living donor clinics at which subjects are identified, who after screening are found to be fit for donation but do not proceed to surgery.
Exclusion criteria for both subjects and controls: These will be the current nationally set exclusion criteria for donors and will include diabetes mellitus, any history of cardiovascular or pulmonary disease, evidence of hypertensive end-organ damage, LV dysfunction (EF < 40%) and atrial fibrillation.49
Primary endpoint: Change in aPWV at 12 months adjusted for mean arterial pressure and heart rate at time of measurement compared with controls.
Secondary endpoints: Change in ambulatory blood pressure, AIx, central aortic pressure and urinary ACR compared with controls.
Secondary analysis: Change in endpoints will be analysed according to baseline GFR, change in GFR, pre-donation hypertension and ethnic group.
Investigations:
The following investigations will be performed in all subjects and controls at baseline (<6 weeks pre-donation) and 1 year post-donation. Subjects and controls will undergo routine follow up by the renal team with no alteration to normal care. No restrictions will be made to the introduction of any treatment including anti-hypertensive drugs. At baseline BMI, blood pressure and heart rate will be recorded. Routine haematological and biochemical parameters including lipids will be recorded. The following additional parameters will be determined:
- Arterial stiffness: A Sphygmocor device will be used to measure parameters including aPWV, AIx and central aortic pressure.
- Spot urine samples will be collected for measurement of ACR.
- Clinic blood pressure
- 24-hour ambulatory blood pressure studies (24h ABPM)
- Isotope GFR for kidney donors will be measured using the renal clearance of 51Cr EDTA50, in keeping with national recommendations. Kidney function in controls will be estimated using MDRD eGFR to minimise radiation exposure and cost.
STATISTICS The original recruitment target was 800 patients. Power calculations used a SD of 1.0 m/s in aPWV and 10 mm Hg in blood pressure and a sample size of 800 patients (control and donors, 400 subjects each). This gives 80% power to detect a difference of 0.22 m/s or 2.2 mm Hg for aPWV and blood pressure allowing for 9% drop out. This is a 2-sided t test at the 2.5% significance level. During the study it was apparent the original recruitment target would not be met therefore a new sample size was calculated.
New power calculations:
Using a SD of 1.0m/s in aPWV and a sample size of 400 patients (control and donors, 200 subjects each). This gives a 92% power to detect a difference of 0.4m/s for aPWV and 4mm Hg for blood pressure allowing for 15% drop out (alpha at 5%). This is a 2-sided t test at the 2.5% significance level. Following this we aimed for a sample size of 400 patients (200 controls and 200 donors) for determination of the primary outcome of PWV in both groups.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
-
Birmingham, United Kingdom, B17 0HT
- University Hospital Birmingham NHS Foundation Trust
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- A donor group will be recruited from all patients undergoing donor nephrectomy.
- A contemporaneous control group will be recruited from clinics, advertisements within and outside the institutions and from any local volunteer databases.
Exclusion Criteria:
- These will be the same for donors and controls. The current nationally set exclusion criteria for donors include age/glomerular filtration rate (GFR) cutoff, diabetes mellitus, any history of cardiovascular or pulmonary disease, evidence of hypertensive end-organ damage, known left ventricular dysfunction (including ejection fraction < 40%) and atrial fibrillation.
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Live kidney donors
Nephrectomy
|
Nephrectomy for the purposes of living kidney donation
|
Healthy controls
Who also meet criteria to donate a kidney
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Aortic Pulse Wave Velocity (aPWV) adjusted for mean arterial pressure and heart rate
Time Frame: 12 months
|
12 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinic blood pressure
Time Frame: 12 months
|
12 months
|
|
Number of patients newly diagnosed with hypertension
Time Frame: 12 months
|
As defined by commencement of antihypertensive therapy
|
12 months
|
Augmentation index (AIx)
Time Frame: 12 months
|
12 months
|
|
Central blood pressure
Time Frame: 12 months
|
Central haemodynamics
|
12 months
|
N-terminal prohormone of brain natriuretic peptide (NT-proBNP)
Time Frame: 12 months
|
12 months
|
|
Urinary albumin: creatinine ratio (ACR)
Time Frame: 12 months
|
12 months
|
|
24 hr Ambulatory Systolic Blood Pressure
Time Frame: 12 months
|
12 months
|
Collaborators and Investigators
Collaborators
Investigators
- Study Chair: John Cockcroft, PhD, Cardiff
- Study Director: Ian B Wilkinson, Cambridge Heart Inc.
- Principal Investigator: Jonathan N Townend, Birmingham
Publications and helpful links
General Publications
- Moody WE, Tomlinson LA, Ferro CJ, Steeds RP, Mark PB, Zehnder D, Tomson CR, Cockcroft JR, Wilkinson IB, Townend JN. Effect of A Reduction in glomerular filtration rate after NEphrectomy on arterial STiffness and central hemodynamics: rationale and design of the EARNEST study. Am Heart J. 2014 Feb;167(2):141-149.e2. doi: 10.1016/j.ahj.2013.10.024. Epub 2013 Nov 6.
- Price AM, Greenhall GHB, Moody WE, Steeds RP, Mark PB, Edwards NC, Hayer MK, Pickup LC, Radhakrishnan A, Law JP, Banerjee D, Campbell T, Tomson CRV, Cockcroft JR, Shrestha B, Wilkinson IB, Tomlinson LA, Ferro CJ, Townend JN; EARNEST investigators. Changes in Blood Pressure and Arterial Hemodynamics following Living Kidney Donation. Clin J Am Soc Nephrol. 2020 Sep 7;15(9):1330-1339. doi: 10.2215/CJN.15651219. Epub 2020 Aug 25.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- A092761
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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 Living Kidney Donors
-
Amit GargCanadian Institutes of Health Research (CIHR)CompletedLiving Kidney DonorsUnited States, Canada, Australia
-
Mayo ClinicNational Institute of Allergy and Infectious Diseases (NIAID)RecruitingTransplantation, Kidney | Living DonorsUnited States
-
Johns Hopkins UniversityUniversity of Maryland, Baltimore; The Living Legacy FoundationActive, not recruitingNephrectomy | Kidney | Living DonorsUnited States
-
Johns Hopkins UniversityNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Vanderbilt... and other collaboratorsActive, not recruitingNephrectomy | Kidney | Living DonorsUnited States
-
Samsung Medical CenterCompletedKidney Transplantation | Living DonorsKorea, Republic of
-
Baylor Research InstituteEnrolling by invitation
-
Weill Medical College of Cornell UniversityCompletedKidney Transplantation | Nephrectomy | Living Donors | Surgery, LaparoscopicUnited States
-
National Institute of Allergy and Infectious Diseases...CompletedLiving Donors | Tissue Donors
-
Oslo University HospitalCompleted
-
University of CologneRecruiting
Clinical Trials on Nephrectomy
-
First Affiliated Hospital of Gannan Medical UniversityUnknown
-
I.M. Sechenov First Moscow State Medical UniversityRecruitingUrolithiasisRussian Federation
-
University Health Network, TorontoWithdrawn
-
Samsun Liv HospitalOndokuz Mayıs UniversityCompletedKidney Neoplasms | Urologic Neoplasms | Renal Cell Carcinoma | Surgery | Kidney Injury | Renal Cancer | Oncology | Urologic Cancer | Renal Neoplasm | Kidney IschemiaTurkey
-
Central Hospital, Nancy, FranceCompletedKidney TransplantationFrance
-
Azienda Socio Sanitaria Territoriale degli Spedali...UnknownGlomerular Filtration Rate | Nephrectomy | Kidney NeoplasmItaly
-
Oslo University HospitalUniversity of Oslo; South-Eastern Norway Regional Health AuthorityActive, not recruitingCardiovascular DiseasesNorway
-
Saint Petersburg State University, RussiaCompletedRenal Tumor | Renal Malignant TumorRussian Federation
-
St. Joseph's Healthcare HamiltonUnknown
-
Mansoura UniversityCompletedRenal Transplant Donor of Left Kidney