Towards HOMe-based Albuminuria Screening: an Implementation Study Testing Two Approaches (THOMAS)

Chronic Kidney Disease (CKD) is a worldwide major public health problem that is associated with an increased incidence of kidney failure and cardiovascular events, that lead a high burden for affected patients and high costs for society. Symptoms of CKD occur late, when kidney function drops to below 30%. At that time preventive measures will have only limited efficacy. Protein excretion in urine has increasingly been recognized as early marker of CKD, and is often associated with high blood pressure, diabetes, and/or high cholesterol levels. These are all important risk factors for progression of kidney and cardiovascular disease. Population screening for urinary protein loss could detect a considerable number of subjects with yet unknown risk factors for progressive kidney and cardiovascular disease who can benefit of early intervention. However, there is no validated method for population screening yet. The aim is to to develop a home based population screening for elevated urinary protein loss. Two screening methods will be investigated, and yield and cost-effectiveness of these screening methods will be evaluated

Study Overview

• Status: Enrolling by invitation
• Conditions: Albuminuria
• Intervention / Treatment: Diagnostic test: Approach A (PeeSpot urine collection device).; Diagnostic test: Approach B (ACR | EU Test kit).

Detailed Description

Chronic kidney disease (CKD) is a worldwide major public health problem that is associated with an increased incidence of kidney failure and cardiovascular disease (CVD). To tackle this burden, screening for CKD among the general population could be beneficial to allow early detection and treatment. In the last decades, elevated albuminuria has increasingly been recognized as an early marker of generalized vascular endothelial damage, that predicts CKD and CVD progression.

It has been estimated that approximately 6% of the general population has elevated albuminuria, and that the majority of these subjects are not known yet with this abnormality. Among these subjects, many have hypertension, hyperlipidemia, diabetes and/or impaired kidney function, that often is also not known yet. Early detection of elevated albuminuria may be important because it gives the opportunity to invite subjects that test positive for further screening for CKD and CVD risk factors. Thus these risk factors for CKD and CVD progression could be treated in an early stage.

Population screening for albuminuria could be justified according to the WHO criteria of Wilson and Jungner , because CKD has important consequences for subjects, the course of the disease is initially symptomless, and there are treatment methods available. However, implementation research to validate screening the general population for albuminuria and related health consequences is lacking, as are cost-effectiveness studies.

In the current study the aim is to develop a home-based screening technique for detecting elevated albuminuria. Two screening methods will be investigated, and yield and cost-effectiveness of these screening methods will be evaluated

• Study Type: Interventional
• Enrollment (Anticipated): 15032
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9700 RB
    • University Medical Centre Groningen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 45 to 80 years.
• Living in the municipality of Breda, The Netherlands.
• Not institutionalised.

Exclusion Criteria:

• Younger than 45 years or older than 80 years.
• Not living in the municipality of Breda, The Netherlands.
• Institutionalised.

A random sample of 15.032 subjects will be drawn from the population aged 45-80 years from the municipality of Breda by the Dutch Central Bureau for Statistics (CBS).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group A; Group A will receive an invitation for home based albuminuria screening using a more conventional urine collection device (known as "Peespot Test").	Diagnostic test: Approach A (PeeSpot urine collection device).; The participant will receive the PeeSpot urine collection device (Hessels+Grob B.V., Deventer, The Netherlands), which consists of a holder containing a urine collection pad (consisting of hygroscopic material containing). The holder can be placed back into the tube and can be easily sent to the laboratory by mail. In this urine, albumin, creatinine, and the ACR will be measured in the laboratory of the Amphia hospital.
Active Comparator: Group B; Group B will receive an invitation for home based albuminuria screening using an app (internet application) and an ACR dipstick test (known as "ACR| EU Test").	Diagnostic test: Approach B (ACR | EU Test kit).; The participant will receive the ACR | EU test kit (Healthy.io Ltd, Tel-Aviv- Yafo, Israel), which consists of a urine test strip, a urine cup, a color calibrator and instruction to download a smartphone application. The participants have to download the smartphone application according to the instructions included in the kit. Results will be directly shown to the participant in the app.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participation rate of the screening (i.e. home-based screening, elaborate screening and overall screening program)	The participation rate is defined as the number of persons completing the albuminuria screening (i.e. returning the first PeeSpot urine device or scanned the first ACR | EU urine test strip with use of the app, and in case of an ACR >30 mg/g in this initial test, also completing the a confirmatory albuminuria screening tests), elaborate screening and overall screening program relative to the invited number of individuals.	Screening period of 6 months.
The yield of albuminuria screening.	These are twofold. First, the yield of the home-based screening is defined as the number of persons who test positive for albuminuria (at least 2 tests positive) relative to the number of persons participating in the corresponding arm (=per-protocol analysis) and of all invited persons in the corresponding arm (intention-to-screen analysis). Second, the yield of the elaborate screening is defined as the number of subjects with increased albuminuria (defined as ACR >30 mg/g) with newly diagnosed and/or poorly controlled CVD and CKD risk factors. These risk factors, which will be assessed during the elaborate screening, include hypertension, diabetes mellitus, hyperlipidemia, impaired kidney function.	Screening period of 6 months.
Cost-effectiveness of the screening.	Incremental cost-effectiveness ratio (ICER) in euro per QALY gained for the two screening methods;	6 months follow-up after screening period.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GP follow-up rate.	Number of persons completing the complete study (ACR testing, elaborate screening when invited, and visiting GP when recommended) relative to the number of referred individuals.	Screening period of 6 months.
Characteristics of responders.	Information on (differences in) characteristics of the responders of the two screening methods (PeeSpot vs. ACR | EU) including differences in age, sex, educational level, estimated social economic status (based on data of Statistics Netherlands, providing estimated social economic status based on postal codes), medication use, and history of disease	Screening period of 6 months.
Characteristics of non-responders.	Information on (differences in) characteristics of the non-responders of the two screening methods (PeeSpot vs. ACR | EU) including differences in age, sex, and estimated social economic status.	Screening period of 6 months.
Usability scores of the two screening methods.	Usability of both tests assessed by questionnaire in the participants with a confirmed positive test and in a subgroup of participants with a negative test.	6 months follow-up after screening period.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Appropriate treatment after elaborate screening.	Evaluate whether the subjects who participated the elaborate screening and in which abnormalities were found (hypertension, diabetes, hypercholesterolemia, impaired renal function) did visit their general practitioner for start of appropriate treatment (lifestyle advice and/or medication).	6 months follow-up after screening period.
Information regarding sensitivity and specificity of the home-based screening tests	Information on rate of false-negative and -positive tests for both screening methods (PeeSpot vs. ACR | EU).	Screening period of 6 months.
Optimal cut-off value of albuminuria.	To investigate which cut-off value of albuminuria should be used in the screening to render the most effective screening.	6 months follow-up after screening period.
Optimal age range for albuminuria screening.	Investigate the most effective age range for albuminuria screening.	6 months follow-up after screening period.
Role of health literacy in albuminuria screening.	The role of health literacy (assessed by questionnaire) in participating in the screening program and by obtaining appropriate treatment by the GP.	6 months follow-up after screening period.

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Collaborators: Dutch Kidney Foundation; Amphia Hospital; Healthy.io Ltd.; E-Zorg B.V. / KPN Health; Hessels+Grob; Copernicus Interchange Technology B.V.
• Investigators: Principal Investigator: Ron T Gansevoort, MD, PhD, University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2019
• Primary Completion (Anticipated): April 1, 2022
• Study Completion (Anticipated): July 1, 2022

Study Registration Dates

• First Submitted: March 2, 2020
• First Submitted That Met QC Criteria: March 2, 2020
• First Posted (Actual): March 5, 2020

Study Record Updates

• Last Update Posted (Actual): April 5, 2022
• Last Update Submitted That Met QC Criteria: March 25, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: hypertension; cardiovascular disease; chronic kidney disease; diabetes mellitus; hypercholesterolemia; app; population screening; e-Health; albuminuria; home based
• Additional Relevant MeSH Terms: Urologic Diseases; Urological Manifestations; Urination Disorders; Proteinuria; Albuminuria
• Other Study ID Numbers: LSHM17076-SGF

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