Condition category
Urological and Genital Diseases
Date applied
26/09/2013
Date assigned
08/10/2013
Last edited
05/09/2014
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Mr Ryan Ottridge

ORCID ID

Contact details

Birmingham Clinical Trials Unit
Division of Medical Sciences
Robert Aitken Institute
Edgbaston
Birmingham
B15 2TT
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

HTA: 11/103/01, UKCRN ID:15268

Study information

Scientific title

Accuracy of glomerular filtration rate (GFR) estimation using creatinine and cystatin C and albuminuria for monitoring disease progression in patients with stage 3 chronic kidney disease - prospective longitudinal study in a multi-ethnic population: the eGFR-C study

Acronym

eGFR-C

Study hypothesis

The eGFR-C study will assess the accuracy of current and alternative tests of kidney function against a reference test in people with moderate (stage 3) chronic kidney disease (CKD).

More details can be found at: http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=15268
More details can be found at: http://www.nets.nihr.ac.uk/projects/hta/1110301
Protocol can be found at http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0020/85403/PRO-11-103-01.pdf

Ethics approval

South East Coast – Surrey REC, 09/10/2013, ref 13/LO/1349

Study design

Observational prospective longitudinal cohort study

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Hospitals

Trial type

Screening

Patient information sheet

Patient information can be found at http://www.birmingham.ac.uk/research/activity/mds/trials/bctu/trials/renal/egfr-c/participants/sheet.aspx

Condition

Topic: Renal and Urogenital; Subtopic: Renal and Urogenital (all Subtopics); Disease: Renal

Intervention

Main study: 1300 patients. Biological variability study: In a sub-study 20 participants will undergo the reference test four times over four weeks and then exit the study.

Iohexol GFR tests, 1300 participants will undergo baseline (month 0) and final (month 36) reference GFR, estimated GFR (eGFR) and urinary albumin-to-creatinine ratio (ACR) tests. Additionally they will provide ACR and eGFR tests at 6-monthly intervals. A subset of the cohort (n=375) will receive annual reference GFR tests.

Participants will be recruited from hospital clinics and GP practices at six major UK centres.

Participants will undergo reference GFR testing at study entry with a second follow-up reference test three years later. The reference test involves injecting a small amount of iohexol into a vein and taking blood samples over the next 4 hours to see how quickly the iohexol disappears from the blood stream as a result of glomerular filtration. The rate at which iohexol disappears is equivalent to the level of kidney function. Blood tests for monitoring kidney function, including testing for creatinine and cystatin C, and measurement of urinary albumin will be done every six months during the study period. Iohexol measured GFR will be accepted as the reference (‘gold standard’) measure of kidney function against which each GFR-estimating equations will be compared. The alternative estimated measures of GFR, derived from measuring substances (creatinine and cystatin C) in the blood, will be compared against the reference test. An important outcome is how much the reference test changes over the three years of the study, and how well the surrogate measures reflect this change. We will also collect accurate test cost data for subsequent cost-effectiveness analysis (e.g. do the relative costs of the tests justify any change in practice due to improved performance of one test compared to another?).

Follow-up length: 36 months

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

1. To estimate and compare the accuracy and precision of GFR-estimating equations based on the Modification of Diet in Renal Disease (MDRD) equation and three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations using either creatinine or cystatin C or a combination of both in people with stage 3 CKD.
2. To estimate the accuracy and precision of the GFR-estimating equations according to ethnic group (particularly Caucasians, African-Caribbean and South-Asian), and baseline diabetes and proteinuria.
Percentage error in eGFR compared to reference GFR. Values will be computed (primary outcome measures 1 and 2) using baseline data for each of the four eGFR equations, and the proportions within 30% (P30) of the reference standard quoted and compared as a measure of accuracy and precision.
3. To evaluate and compare how accurately these GFR-estimating equations reflect change in GFR over three years. Difference in rate of change in eGFR compared to rate of change in reference GFR. Rates of change will be estimated using linear regression and the change per annum and percentage change per annum compared to baseline values will be computed. Large error will be defined as differing by more than 3 mL/min/1.73 m^2/year or by 5 percent points per annum.

Secondary outcome measures

1. To establish which GFR-estimating equation, together with ACR, or ACR alone, most accurately predicts those people that have progressive loss of kidney function (CKD progression). Progressive loss of kidney function defined as decline in GFR of more than 10 mL/min/1.73 m^2/3 years or increase in albuminuria category as defined by Kidney Disease: Improving Global Outcomes (KDIGO).
2. To compare the effectiveness and costs of monitoring strategies for identifying people that have progressive loss of kidney function (CKD progression) utilising different GFR-estimating equations and test schedules, accounting for differences in risk of progression. Measured using Cost per quality-adjusted life-year (QALY).

Sub-study of patterns of disease progression
To estimate and model disease progression (decline in GFR or increase in ACR) according to ethnic group (particularly Caucasians, African-Caribbean and South-Asian), and baseline diabetes and proteinuria. Difference in rate of change in eGFR compared to rate of change in reference GFR based on measurements made every 12 months.

Additional study of intra-individual biological variation
Within-individual (CVI) variation and the critical difference (reference change value, RCV) for reference GFR and the estimated GFR equations.

Overall trial start date

01/02/2014

Overall trial end date

31/07/2015

Reason abandoned

Eligibility

Participant inclusion criteria

1. Male and female, aged 18 years or over
2. Patients with stage 3 CKD (GFR 30-59 mL/min/1.73 m2) as defined internationally, diagnosed using Modification of Diet in Renal Disease/Chronic Kidney Disease Epidemiology Collaboration (MDRD/CKD EPI) eGFR (at least two consecutive test results in this range at least 90 days apart, with the most recent test in the last 12 months)
3. Written informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 1320; UK Sample Size: 1320

Participant exclusion criteria

1. History of untoward reactions to iodinated contrast media or allergy to topical iodine
2. Episode of acute kidney injury in previous 6 months (as defined by the Acute Kidney Injury Network criteria)
3. Amputation of whole or part limb
4. Pregnant or breastfeeding
5. Known alcohol or drug abuse
6. Any clinical condition with an expected survival of less than study duration
7. Inability to comply with study schedule and follow-up
8. Inability to provide informed consent e.g. due to cognitive impairment

Recruitment start date

01/02/2014

Recruitment end date

31/07/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Birmingham Clinical Trials Unit
Birmingham
B15 2TT
United Kingdom

Sponsor information

Organisation

University of Birmingham (UK)

Sponsor details

Edgbaston
Birmingham
B15 2TT
United Kingdom

Sponsor type

University/education

Website

http://www.birmingham.ac.uk

Funders

Funder type

Government

Funder name

NIHR Health Technology Assessment Programme - HTA (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2014 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/24423077

Publication citations

  1. Protocol

    Lamb EJ, Brettell EA, Cockwell P, Dalton N, Deeks JJ, Harris K, Higgins T, Kalra PA, Khunti K, Loud F, Ottridge RS, Sharpe CC, Sitch AJ, Stevens PE, Sutton AJ, Taal MW, , The eGFR-C study: accuracy of glomerular filtration rate (GFR) estimation using creatinine and cystatin C and albuminuria for monitoring disease progression in patients with stage 3 chronic kidney disease--prospective longitudinal study in a multiethnic population., BMC Nephrol, 2014, 15, 13, doi: 10.1186/1471-2369-15-13.

Additional files

Editorial Notes