Systematic NT-proBNP and ECG Screening for Atrial Fibrillation Among 75 Year Old Subjects in the Region of Stockholm, Sweden - STROKESTOP II (STROKESTOP II)

STROKESTOP II will study if the biomarker NT-proBNP together with single-lead ECG can be used as a primary population screening tool for silent atrial fibrillation, and builds on previous results from the STROKESTOP study.

Study Overview

• Status: Active, not recruiting
• Conditions: Stroke; Atrial Fibrillation
• Intervention / Treatment: Other: ECG screening (Zenicor-ECG) for atrial fibrillation

• Study Type: Observational
• Enrollment (Actual): 6868

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 11361
    • Karolinska Trial Alliance, KTA Prim

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 75 years to 76 years (Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Individuals aged 75/76 residing in Stockholm will be identified using their 10-digit personal identification number. All identified subjects will be randomized in a 1:1 fashion to be invited to screening for AF or to serve as a control group.

Participants with a prior diagnosis of AF will be asked if they are on treatment with anticoagulants. If they are not, a referral to cardiologist will be made to ensure appropriate treatment.

Individuals without known AF will have blood samples drawn and analysed with regard to NT-proBNP using point of care analysis.

All individuals with NT-proBNP> 125 ng/L and without known AF will be taught to undergo intermittent ECG recordings twice daily for two weeks (High-risk Group). Individuals with a NT-proBNP<125 ng/L will do one initial 1-lead ECG, and if normal not undergo further ECG screening (low-risk Group).

Description

Inclusion Criteria:

• Individuals born 1940 and 1941 residing in Stockholm at the time of inclusion

Exclusion Criteria:

• Not fulfilling the inclusion criteria

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ECG screening; Will be screened for AF using only one-stop protocol	Other: ECG screening (Zenicor-ECG) for atrial fibrillation; Determination of the biomarker NT-proBNP together with single-lead ECG screening for silent atrial fibrillation.
Control group; as per regular standard as of today

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of stroke or systemic embolism in the control group vs the intervention group	Endpoints collected from the Swedish patient registry will be compared between the groups	Five years
Incidence of stroke or systemic embolism in the control group vs the low-risk group (with NT-proBNP<125 ng/L and normal index 1-lead ECG).	Endpoints collected from the Swedish patient registry will be compared between the groups	Five years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of major bleeding, ischaemic stroke, systemic embolism and death in the control group vs the intervention group	Endpoints collected from the Swedish patient registry will be compared between the groups	Five years
Number of subjects with new discovered AF using intermittent ECG-recordings in the high risk Group with NT-proBNP>125 ng/L.	All individuals with NT-proBNP>125ng/L will undergo intermittent ECG recordings at least twice daily for two weeks.	Two years
To assess screening uptake with regards to socio-demographic factors and to study if we can improve uptake in the screening programme by decentralizing the recruitment procedure.	Participants and non-participants will be compared using socioeconomic data provided by statistics sweden	Two years
Cost per gained quality-adjusted life-year (QALY) and cost per avoided stroke of the STROKESTOP II screening program.	With the same statistical methods used in STROKESTOP I, the number of fewer years with undetected AF will be calculated as well as the number of avoided strokes, the number of life-years and the number of quality-adjusted life years (QALYs) per 1000 screened patients. The result will be reported as the incremental cost per gained QALY and per avoided stroke.	Five years
Plasma and serum biomarkers and their relation to incidence of new AF and short episodes of AF (micro-AF)	serum and plasma biomarkers within coagulation, inflammation, cardiomyocyte stress, atrial fibrosis, electrical remodelling, prothrombotic state and altered haemodynamics will be analysed with immunoassays, in order to identify the best discriminator for silent AF on population level. https://www.olink.com/products/cvd-iii-panel/	Five years
To assess the incidence of heart failure in patients with NT-proBNP>125ng/L	To assess the value of structured follow-up with echocardiography in participants without known heart failure, but with increased NT-proBNP as a method to diagnose heart failure with reduced and preserved ejection fraction; and to assess whether in patients with NT-proBNP > 125 pg/mL, a higher cut-off can be used to predict HF on echocardiography, and thus be used to triage asymptomatic patients to echocardiography.	Five years
To study atrial function in patients with and without silent atrial fibrillation	In a subset of participants with and without atrial fibrillation, advanced atrial echocardiography will be performed	Five years
To study the correlation between symptoms and newly discovered AF	Participants are asked if they have had symptoms of palpitations before screening visit	Four years
To study the diagnostic performance of pulse-palpation in AF screening as compared to one-lead ECG	pulse palpation will be performed in all participants and then a single-lead ECG will be registered	Four years
To study the association of very short episodes of AF (micro-AF, episodes lasting shorter than 30 seconds) and incident AF	Individuals with micro-AF, defined as at least five supraventricular ectopics in a row but lasting shorter than 30 seconds at any time during intermittent screening will be compared to participants without micro-AF with regard to incident AF during screening.	Two years
To compare different ECG modalities for AF screening	A subset of participants will perform both single-lead, handheld, intermittent ECG (Zenicor) and continuous event loop ECG recordings (Novacor R-test 4) and AF yield (defined as at least one episode of AF with a duration of 30 seconds) will be compared between the methods. Tolerability to both methods will be measured qualitatively with a questionnaire.	Two years
Incidence of undiagnosed hypertension in participants	Blood pressure will be measured and participants with elevated blood pressure but no previous diagnosis of hypertension will be referred for further evaluation	four years

Collaborators and Investigators

• Sponsor: Karolinska University Hospital
• Collaborators: Roche Diagnostics
• Investigators: Principal Investigator: Mårten Rosenqvist, MD, Karolinska Institutet

Publications and helpful links

General Publications

• Fredriksson T, Gudmundsdottir KK, Frykman V, Friberg L, Al-Khalili F, Engdahl J, Svennberg E. Brief episodes of rapid irregular atrial activity (micro-AF) are a risk marker for atrial fibrillation: a prospective cohort study. BMC Cardiovasc Disord. 2020 Apr 10;20(1):167. doi: 10.1186/s12872-020-01453-w.

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Anticipated): April 1, 2023
• Study Completion (Anticipated): April 1, 2023

Study Registration Dates

• First Submitted: March 16, 2016
• First Submitted That Met QC Criteria: April 14, 2016
• First Posted (Estimate): April 19, 2016

Study Record Updates

• Last Update Posted (Actual): November 25, 2020
• Last Update Submitted That Met QC Criteria: November 20, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Screening; Cost effectiveness; Stroke prevention
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: STROKESTOP II

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO