Responding to AF: Pill-in-Pocket Anticoagulation Guided by Automated Monitoring and Alerts (RESPOND-AF)

August 7, 2026 updated by: Tim Betts MD MBChB FRCP, Oxford University Hospitals NHS Trust

Pill-in-Pocket Oral Anticoagulation Responding to Atrial Fibrillation Episodes Guided by Continuous Rhythm Monitoring and Automated Smartphone Alerts

Atrial Fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting 1-2 million people in the UK. AF is characterised by uncoordinated electrical activation and ineffective contraction of the upper cardiac chambers. AF can occur in temporary episodes, as in paroxysmal AF, or can be sustained continuously beyond 7 days' duration, as in persistent AF.

The most significant potential complication of AF is stroke caused by a blood clot (thromboembolic stroke). If untreated, the risk of stroke in AF can be increased as much as five-fold, depending on the presence of other risk factors.

The mechanism of thromboembolic stroke in AF patients is complicated and understanding of factors involved remains incomplete. AF has been shown to disrupt normal bodily mechanisms for controlling bleeding and clotting (haemostasis) and normal blood flow inside the cardiac chambers. In disrupting these mechanisms, AF can be said to create a 'prothrombotic' state or environment within the blood and heart (a tendency to form clots) which can lead to blood clot formation and subsequently to stroke.

There is research evidence that AF-related stroke risk is not fixed and changes over time. This dynamic risk may be related to the episodic nature of AF, with stroke risk changing during an episode of AF and for a period of weeks after the episode terminates.

Analytic studies have shown that the risk of stroke is highest in the days after an AF episode has occurred, peaking at 5 days and returning to baseline by 30 days. Other studies have shown that the duration of the AF episode can also influence the risk of stroke following each episode, with longer episodes being higher risk.

This dynamic risk likely relates to changes in the activation of the body's blood-clotting system and changes in blood flow within the heart.

Current clinical guidelines recommend that patients with AF and risk factors for stroke are treated with daily, uninterrupted anticoagulation (blood-thinning medication) to reduce the risk of stroke. These guidelines do not take into account the temporal pattern of AF or the frequency or duration of AF episodes.

An emerging approach to anticoagulation in AF is pill-in-pocket oral anticoagulation (PIPOAC). In this approach, AF patients only take their anticoagulation in response to episodes of AF, and for a period of time after normal heart rhythm is restored. This approach may suit AF patients who have lower risk, lower frequency AF and who wish to reduce their exposure to anticoagulation medication. It may also suit AF patients who have higher bleeding risk related to anticoagulation.

The RESPOND-AF study proposes a novel approach to delivering PIPOAC. It is a pilot study of this novel approach recruiting 50 participants. This includes participants having continuous heart rhythm monitoring using the Medtronic LINQ II implantable cardiac monitor. The LINQ II continuously monitors for evidence of AF. If AF is detected a transmission is uploaded to the Medtronic Carelink cloud portal.

Traditionally, healthcare professionals need to sign in to this portal to check for any transmissions. For the purposes of PIPOAC this traditional approach would be too slow and create a burdensome workload for clinicians. Due to the properties of blood clot formation in AF, it is important to initiate oral anticoagulation within 48 hours of AF episode onset to disrupt the clot-formation process.

For the purposes of this study, the investigators have developed a custom-designed software which continuously screens for transmissions of AF on the Carelink cloud portal. When an AF episode has been detected by the LINQ II monitor, the software will send an SMS smartphone alert to the patient informing them of the AF episode and instructing them to commence their oral anticoagulation as soon as possible. This approach, if shown to be safe and effective and acceptable to patients, could open the path to wider use of Pill-in-pocket oral anticoagulation.

This novel treatment can reduce the need for anticoagulation, meaning fewer bleeding complications. Pill-in-pocket oral anticoagulation empowers patients by offering a new treatment choice beyond current limited options.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Oxfordshire
      • Oxford, Oxfordshire, United Kingdom, OX3 9DU
        • Oxford University Hospitals NHS Trust, John Radcliffe Hospital

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

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Participant is willing and able to give informed consent for participation in the trial.
  2. Understand the risk and willing to discontinue oral anticoagulation (OAC).
  3. Any gender aged 18 years or above.
  4. Non-valvular paroxysmal atrial or persistent atrial fibrillation (AF) with a current rhythm control strategy. Paroxysmal patients must have < 3 documented or symptomatic episodes of >1 hour duration in the previous 3 months. Persistent patients must have been in continuous sinus rhythm for at least 4 weeks prior to enrolment.
  5. CHA2DS2-VASc score between 1 and 3 in men and between 2 and 4 in women.
  6. Able to take direct-acting oral anticoagulant (DOAC) in guideline recommended doses.
  7. Left atrial (LA) diameter on echocardiogram less than 5 cm (anteroposterior dimensions) or LA volume less than 48 ml/m2.

Exclusion Criteria:

  1. Any contraindication to OAC therapy with a DOAC in guideline recommended doses.
  2. Mechanical heart valve prosthesis or moderate-to-severe mitral valve stenosis.
  3. Permanent atrial fibrillation.
  4. Hypertrophic cardiomyopathy.
  5. Documented previous thromboembolic event (stroke, transient ischaemic attack or systemic embolism).
  6. Spontaneous echo contrast observed in any imaging modality.
  7. History of intracardiac thrombi.
  8. History of congenital heart disease.
  9. Severe chronic renal disease (eGFR <15 ml/m) or on renal replacement therapy.
  10. Pregnant or planning pregnancy.
  11. Indication for OAC other than atrial fibrillation.
  12. Inability to comply with protocol.
  13. Smartphone with operating system (OS) not compatible with MyCareLink Heart app.
  14. Contraindication for implantable cardiac monitor.
  15. Visual or physical impairment that prevents ability to read and acknowledge smartphone/watch notifications.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pill-in-pocket anticoagulation
Participants will stop their oral anticoagulation after a 30-day period free of AF episodes. After this, they will only take their anticoagulation in response to an episode of AF detected by their implantable cardiac monitor. The participants will receive an automated smartphone alert instructing them to commence their anticoagulation as soon as AF is detected.
Other: Pill-in-pocket anticoagulation
Participants will stop their oral anticoagulation after a 30-day period free of AF episodes. After this, they will only take their anticoagulation in response to an episode of AF detected by their implantable cardiac monitor. The participants will receive an automated smartphone alert instructing them to commence their anticoagulation as soon as AF is detected.
Other Names:
  • As-required anticoagulation
  • Intermittent anticoagulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To investigate the reduction in oral anticoagulation (OAC) utilisation during follow-up.
Time Frame: During follow-up (minimum 13 months)
Calculate the proportion of time off anticoagulation OAC
During follow-up (minimum 13 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Thromboembolic events (Ischaemic stroke, transient ischaemic attack (TIA) and systemic embolism)
Time Frame: During follow-up (minimum 13 months)
Calculate the rate of ischaemic stroke, TIA and systemic embolism in patients on as-required OAC
During follow-up (minimum 13 months)
Major bleeding
Time Frame: During follow-up (minimum 13 months)
Calculate the rate of major bleeding in patients on as-required OAC
During follow-up (minimum 13 months)
Minor bleeding
Time Frame: During follow-up (minimum 13 months)
Calculate the rate of minor bleeding in patients on as-required OAC
During follow-up (minimum 13 months)
Any stroke (ischaemic, haemorrhagic or undetermined)
Time Frame: During follow-up (minimum 13 months)
Calculate the stroke rate (ischaemic, haemorrhagic or undetermined)
During follow-up (minimum 13 months)
All-cause mortality
Time Frame: During follow-up (minimum 13 months)
Calculate the rate of all-cause mortality in patients on as-required OAC
During follow-up (minimum 13 months)
Protocol adherence
Time Frame: During follow-up (minimum 13 months)
Calculate the number of daily transmissions and percentage of patients that restarts OAC within 24 hours of the smartphone-alert.
During follow-up (minimum 13 months)
To assess response time from AF episode onset to patient starting as-required OAC
Time Frame: During follow-up (minimum 13 months)
Time from AF episode onset to detection, time to alerts being sent and acknowledged and OAC
During follow-up (minimum 13 months)

Collaborators and Investigators

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

Sponsor

Oxford University Hospitals NHS Trust

Collaborators

Medtronic

Investigators

  • Principal Investigator: Prof Tim R. Betts MD MBChB FRCP, University of Oxford

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 (Actual)

April 14, 2025

Primary Completion (Estimated)

April 30, 2027

Study Completion (Estimated)

July 31, 2027

Study Registration Dates

First Submitted

April 3, 2025

First Submitted That Met QC Criteria

April 9, 2025

First Posted (Actual)

April 10, 2025

Study Record Updates

Last Update Posted (Actual)

August 12, 2026

Last Update Submitted That Met QC Criteria

August 7, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17913
  • IRAS ID 329237 (Other Identifier: HRA (Health Research Authority - United Kingdom))
  • CPMS 56479 (Other Identifier: NIHR (National Institute for Health and Care Research - United Kingdom))
  • 24/WS/0126 (Other Identifier: West of Scotland Research Ethics Service (United Kingdom))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Not included in Informed Consent Form.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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.

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