Assessment of Lipoprotein(a) and Endogenous Fibrinolysis in Atherosclerotic Cardiovascular Disease/Aortic Valve Disease

NCT06126367 | Recruiting

• 1 other identifier: RD2023-43
• Study Type: observational
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

Prior studies have shown that impaired endogenous fibrinolysis is a novel, independent cardiovascular risk factor in patients with myocardial infarction and there is currently no known chronic treatment to enhance endogenous fibrinolysis. To date, no therapies have been able to sufficiently reduce Lp(a) and therefore it was considered to be a non-modifiable cardiovascular risk factor. New data, however, has shown that PCSK9 inhibitors and inclisiran (medication that you have been deemed eligible for in order to help further reduce your cholesterol levels) to reduce Lp(a) levels by approximately 20-25%. The aim of this study to is to assess:

1. 1.if there is an association between raised Lp(a) level in blood and the effectiveness of endogenous fibrinolysis (lysis time).
2. 2.whether lowering Lp(a) with PCSK9i or inclisiran can enhance endogenous fibrinolysis

Conditions

Atherosclerosis; Aortic Valve Disease

Keywords

Lipoprotein (a); Global thrombosis test; Endogenous fibrinolysis

Outcome Measures

Primary Outcomes (2)

• Thrombotic status

  Change in thrombotic status as measured by Lysis Time (LT) using the GTT from baseline to 6-months post initiation of PCSK9i or inclisiran

  3-6 months

• Lipoprotein(a) levels

  Change in lipoprotein(a) levels from baseline to 6-months post initiation of PCSK9i or inclisiran

  3-6 months

Study Arms (2)

Patients identified as eligible for treatment with either a PCSK9i or inclisiran

Diagnostic Test: Thrombotic assessment; Diagnostic Test: Measurement of Lp(a)

Patients with moderate or severe aortic calcification identified by non-enhanced cardiac CT scan

Diagnostic Test: Thrombotic assessment; Diagnostic Test: Measurement of Lp(a)

Interventions

Thrombotic assessment DIAGNOSTIC_TEST

The Global Thrombosis Test (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). Thromboelastography 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. Plasma will be stored for subsequent analysis of other thrombotic, fibrinolytic, inflammatory and coagulation markers as deemed appropriate. For patients deemed eligible for treatment with either a PCSK9i or inclisiran, this will be assessed prior to commencing treatment and also 3-6 months after starting treatment. This will only be assessed once for patients with moderate or severe aortic valve calcification.

Patients identified as eligible for treatment with either a PCSK9i or inclisiran; Patients with moderate or severe aortic calcification identified by non-enhanced cardiac CT scan

Measurement of Lp(a) DIAGNOSTIC_TEST

Lp(a) will be measured by particle enhanced immunotubidimetricassay. Human lipoprotein (a) agglutinates with latex particles coated with anti-Lp(a) antibodies. The precipitate is determined turbidimetrically at 800 / 660 nm. The platform employed will be the Roche® Immunoassay Analyser (Roche Diagnostics GmbH, Sandhofer Strasse 116, D-68305 Mannheim). Traceability: This method has been standardized against the IFCC (International Federation of Clinical Chemistry) reference material SRM2B for nmol/L. For patients deemed eligible for treatment with either a PCSK9i or inclisiran, this will be assessed prior to commencing treatment and also 3-6 months after starting treatment. This will only be assessed once for patients with moderate or severe aortic valve calcification.

Patients identified as eligible for treatment with either a PCSK9i or inclisiran; Patients with moderate or severe aortic calcification identified by non-enhanced cardiac CT scan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

1\) Male and female patients aged 18 years or over. 2\) i) Patients identified as eligible for treatment with either a PCSK9i or inclisiran ii) Patients diagnosed with moderate or severe calcific aortic stenosis based on non enhanced Cardiac CT scan

You may qualify if:

• \) Male and female patients aged 18 years or over
• \) i) Patients identified as eligible for treatment with either a PCSK9i or inclisiran ii) Patients diagnosed with moderate or severe calcific aortic stenosis based on non-enhanced Cardiac CT scan
• \) Willing and able to understand the Participant Information Sheet and provide informed consent
• \) The patient must agree to comply with the drawing of blood samples for the assessments

You may not qualify if:

• Inability to provide valid informed consent
• Male and female patients aged \< 18 years of age
• The patient has, in the opinion of the investigator, significant neurological, hepatic, renal, endocrine, gastrointestinal, pulmonary, haemorrhagic, metabolic or other disease likely to confound the study requirements or analyses
• The patient has a history of substance abuse or demonstrates signs or clinical features of active substance abuse or psychiatric disease
• Alcohol consumption above recommended safe levels (i.e., more than 14 units per week) due to the potential effects of high alcohol levels on platelet reactivity
• Any illness deemed significant by the investigator during the four (4) weeks preceding the screening period of the study
• Any major bleeding diathesis or blood dyscrasia (platelets \< 70 x 109/l, Hb \< 8 g/dl, INR \> 1.4, APTT \> x 2 upper normal limit, leucocyte count \< 3.5 x 109/l, neutrophil count \< 1 x 109/l)
• Currently enrolled in an investigational device or non-licensed drug trial

Sponsors & Collaborators

• East and North Hertfordshire NHS Trust: lead

Study Sites (1)

East and North Herts NHS Trust

Stevenage, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma

MeSH Terms

Conditions

Atherosclerosis; Aortic Valve Disease

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Heart Valve Diseases; Heart Diseases

Study Officials

• Diana A Gorog, MD, PhD

  East and North Hertfordshire NHS Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joshua H Leader, MBChB, BSc

CONTACT

07376188768; joshua.leader@nhs.net

Diana A Gorog, MD, PhD

CONTACT

01707247512; d.gorog@imperial.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 6, 2023
• First Posted: November 13, 2023
• Study Start: October 20, 2023
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: November 13, 2023

Record last verified: 2023-11

Locations

GB (1)