An Investigator-initiated Linked Study to OCEANIC-AF

Assessing the Effect of Asundexian on Thrombotic Status, in Particular Endogenous Fibrinolysis, in Patients With Atrial Fibrillation

Impaired endogenous fibrinolysis is a recently recognised risk factor for thrombotic events in patients with cardiovascular disease. Enhancing endogenous fibrinolysis in such individuals represents a way of reducing thrombosis risk. However, the optimal pharmacotherapy to enhance fibrinolysis is unclear.

The aim of this study is to assess the effect of asundexian on endogenous fibrinolysis and compare this to apixaban. If asundexian can enhance endogenous fibrinolysis, this could be used as targeted treatment for patients who despite optimal antithrombotic therapy, demonstrate impaired endogenous fibrinolysis.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Diagnostic test: Thrombotic assessment

Detailed Description

The risk of a clot forming in a blood vessel, which can cause a heart attack or stroke, is determined partly by how "sticky" the blood is and partly by the effectiveness of the natural defences in the blood in dissolving any clots that start forming (clot lysis, or "fibrinolysis"). There are available tests that can assess how "sticky" the blood is, and we can overcome that with specific blood-thinning medications (such as anticoagulants [such as warfarin, apixaban, rivaroxaban] and antiplatelet agents [such as aspirin and clopidogrel]). However, we have not been able to assess the effectiveness of natural clot dissolving mechanisms, until recently.

In the last few years, using new blood testing techniques, we and other groups, have shown that individuals who have less effective natural clot lysis, have a much higher risk of heart attack, stroke and death. Therefore, we would like to find medications that can make clot lysis more effective, in such individuals, to reduce their risk of stroke and heart attack. Unfortunately, most blood thinning tablets for long term use do not improve clot lysis.

Earlier, our group has shown that the anticoagulant apixaban, mildly improved clot lysis.

We would now like to assess clot lysis in patients taking apixaban and compare it to patients taking a very new type of anticoagulant called asundexian, to see if asundexian can improve clot lysis more than apixaban.

The easiest way to do this, is to test additional blood samples from patients who are already taking part in a clinical trial comparing apixaban and asundexian (OCEANIC-AF). OCEANIC-AF is a phase 3, multicentre, randomised clinical trial, comparing asundexian, a new type of blood thinner (factor XI inhibitor) with a commonly used blood thinner (apixaban, a factor X inhibitor), to see if it carries a lower risk of bleeding.

This is a prospective observational linked study to the main OCEANIC-AF study, to be undertaken in 2 centres in England. Patients enrolled in OCEANIC-AF at these 2 centres will have 4 additional blood samples taken, at baseline before starting the investigational drug or comparator, then at the 3, 6 and 12 month visits.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Joshua H Leader, MBCHB, BSc; Phone Number: 07376188768; Email: joshua.leader@nhs.net
• Study Contact Backup: Name: Diana A Gorog, MD, PhD; Phone Number: 01707247512; Email: d.gorog@imperial.ac.uk

Study Locations

• United Kingdom
  • Liverpool, United Kingdom
    • Not yet recruiting
    • Liverpool Heart and Chest Hospital
    • Principal Investigator: Gregory Lip
    • Contact: Ying Gue; Phone Number: +44(0)151 794 9020; Email: y.gue@nhs.net
    • Sub-Investigator: Ying Gue
  • Stevenage, United Kingdom
    • Recruiting
    • East and North Herts NHS Trust
    • Contact: Toral Odedra; Phone Number: 07918 360 060; Email: grantapplications.enh-tr@nhs.net
    • Principal Investigator: Diana A Gorog
    • Sub-Investigator: Joshua H Leader

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

All patients enrolled into OCEANIC-AF study at these two centres will be approached to also participate in this linked study.

Description

Inclusion Criteria:

1. Patients aged 18 years or over
2. Patients enrolled in OCEANIC-AF study
3. Free from the exclusion criteria below
4. The patient is willing and able to understand the Patient Information Sheet and provide written informed consent
5. The patient agrees to comply with the drawing of blood samples for the assessments.

Exclusion Criteria:

1. Inability to provide valid informed consent
2. Patients aged < 18 years of age
3. Patients with significant neurological, hepatic, renal, endocrine, gastrointestinal, pulmonary, haemorrhagic, metabolic or other disease likely to confound the study requirements or analyses
4. Patients with a history of substance abuse or signs or clinical features of active substance abuse or psychiatric disease
5. Alcohol consumption above 21 units per week
6. Any illness deemed significant by the investigator during the four (4) weeks preceding the screening period of the study
7. Any major bleeding diathesis or blood dyscrasia (platelets <70 x 109/l, Hb <80 g/dl, INR >1.4, APTT >x 2 UNL, leucocyte count <3.5 x 109/l, neutrophil count <1 x 109/l)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Atrial fibrillation; Patients already enrolled in main OCEANIC-AF study.

Diagnostic test: Thrombotic assessment; GTT The Global Thrombosis Test (GTT) (Thromboquest Limited, UK) is an in vitro method imitating high shear stress conditions akin to that which exist in a severely stenosed artery. The test measures platelet reactivity (occlusion time) and endogenous fibrinolysis time (lysis time). TEG Thromboelastography (TEG, Haemonetics Corporation, USA) is a technique that assesses the whole process of clotting and its viscoelastic properties, from the initial activation and aggregation of platelets, to the role of thrombin and finally the stability of the formed clot, as a measure of fibrinolytic resistance. Citrated plasma will be stored for subsequent evaluation of thrombosis and fibrinolysis markers (including but not restricted to D-dimer, PAI-1, hs-CRP, NETs)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thrombotic status	The main marker of interest is endogenous fibrinolysis time (LT)	12 months

Collaborators and Investigators

• Sponsor: East and North Hertfordshire NHS Trust
• Collaborators: Liverpool Heart and Chest Hospital NHS Foundation Trust
• Investigators: Principal Investigator: Diana A Gorog, MD, PhD, East and North Hertfordshire NHS Trust

Study record dates

Study Major Dates

• Study Start (Estimated): November 3, 2023
• Primary Completion (Estimated): September 17, 2026
• Study Completion (Estimated): September 17, 2026

Study Registration Dates

• First Submitted: November 5, 2023
• First Submitted That Met QC Criteria: November 5, 2023
• First Posted (Estimated): November 9, 2023

Study Record Updates

• Last Update Posted (Estimated): November 9, 2023
• Last Update Submitted That Met QC Criteria: November 5, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Atrial fibrillation; Endogenous fibrinolysis; Global thrombosis test
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: RD2023-21

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No