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The Effects of Renal Function and Atrial Fibrillation on Lipoproteins and Clot Structure/Function (RALiC)

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ClinicalTrials.gov Identifier: NCT04043026
Recruitment Status : Not yet recruiting
First Posted : August 2, 2019
Last Update Posted : August 12, 2019
Sponsor:
Collaborators:
Liverpool Centre for Cardiovascular Science
Liverpool Heart and Chest Hospital NHS Foundation Trust
Liverpool John Moores University
University of Leeds
Information provided by (Responsible Party):
Wern Yew Ding, University of Liverpool

Brief Summary:
Atrial fibrillation is a condition whereby participants suffer from an irregular heart. It is the most frequent rhythm disturbance that becomes progressively more common with advancing age. An estimated 25 percent of participants over the age of 70 are affected. It has major implications for individual quality of life and overall healthcare economics. Despite the scale of the problem, there remains much that the investigators do not understand about atrial fibrillation. One such example is in terms of stroke prevention. It is well-accepted that participants with atrial fibrillation are at risk of forming clots within the heart which can travel to the brain and cause a stroke. Therefore, participants are routinely offered blood-thinning medications, such as warfarin, to reduce this risk. However, employing this treatment strategy in participants with concurrent kidney damage appears to be ineffective at reducing stroke risk while still subjecting participants to a significant risk of bleeding. At present, the investigators do not yet understand the mechanism by which this occurs. As a result, there are limited treatment options available for participants with atrial fibrillation and kidney damage. In a previous study, the investigators showed differences in clot properties in atrial fibrillation participants with kidney failure compared to those without. The exact reasons for this observation is not known but may explain why medications do not work for this group of participants. One possible explanation may lie with specific fatty molecules that have been shown to be affected with kidney damage and previously been linked to clot formation. However, this has never been investigated in atrial fibrillation. Therefore, the investigators aim to evaluate the effects of kidney damage on specific fatty molecules, and investigate their role as possible intermediaries to explain changes seen in clot properties. Written consent will be sought prior to recruitment. Blood samples will be collected from participants with atrial fibrillation before and after starting warfarin therapy; participants with atrial fibrillation and/or kidney damage; and participants with atrial fibrillation on stable doses of warfarin who are treated with high-intensity cholesterol-lowering medications. These blood samples will be analysed for specific fat molecules and clot properties using validated laboratory methods, and compared to control groups.

Condition or disease Intervention/treatment
Atrial Fibrillation Chronic Kidney Diseases Drug: Warfarin Drug: Statin

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Study Type : Observational
Estimated Enrollment : 156 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Stratifying Clinical Risk in Patients With Atrial Fibrillation and Chronic Kidney Disease by Studying How Abnormalities in Clot Structure/Function and Lipoproteins Contribute to Thrombosis and Bleeding
Estimated Study Start Date : September 2, 2019
Estimated Primary Completion Date : August 2, 2022
Estimated Study Completion Date : August 2, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Warfarin

Group/Cohort Intervention/treatment
WP1: AF + CKD
Participants with atrial fibrillation (AF) and chronic kidney disease (CKD, defined as eGFR <50 ml/min/1.73m2 for the purposes of this trial), commencing warfarin therapy as part of routine clinical care
Drug: Warfarin
INR-dependent dosage

WP1: AF + no CKD
Participants with atrial fibrillation (AF) and no chronic kidney disease (CKD, defined as eGFR ≥50 ml/min/1.73m2 for the purposes of this trial), commencing warfarin therapy as part of routine clinical care
Drug: Warfarin
INR-dependent dosage

WP2: Group 1 - AF + CKD
Participants with atrial fibrillation (AF) and chronic kidney disease (CKD) who are on stable doses of warfarin
Drug: Warfarin
INR-dependent dosage

WP2: Group 2 - AF + no CKD
Participants with atrial fibrillation (AF) and no chronic kidney disease (CKD) who are on stable doses of warfarin
Drug: Warfarin
INR-dependent dosage

WP2: Group 3 - no AF + CKD
Participants with no atrial fibrillation (AF) and chronic kidney disease (CKD) who are on stable doses of warfarin
Drug: Warfarin
INR-dependent dosage

WP2: Group 4 - no AF + no CKD
Participants with no atrial fibrillation (AF) and no chronic kidney disease (CKD) who are on stable doses of warfarin
Drug: Warfarin
INR-dependent dosage

WP3: AF + CKD
Participants with atrial fibrillation (AF) and chronic kidney disease (CKD, defined as eGFR <50 ml/min/1.73m2 for the purposes of this trial) who are on stable doses of warfarin, commencing statin therapy as part of routine clinical care
Drug: Warfarin
INR-dependent dosage

Drug: Statin
Any statin therapy acceptable




Primary Outcome Measures :
  1. WP1: Clot formation assessment [ Time Frame: Baseline ]
    Clot formation (lag time)

  2. WP1: Clot formation assessment [ Time Frame: After 6 weeks of warfarin therapy ]
    Clot formation (lag time)

  3. WP1: Fibrin structure (maximum absorbance) [ Time Frame: Baseline ]
    Fibrin structure (maximum absorbance)

  4. WP1: Fibrin structure (maximum absorbance) [ Time Frame: After 6 weeks of warfarin therapy ]
    Fibrin structure (maximum absorbance)

  5. WP1: Fibrin permeation analysis [ Time Frame: Baseline ]
    Flow rates

  6. WP1: Fibrin permeation analysis [ Time Frame: After 6 weeks of warfarin therapy ]
    Flow rates

  7. WP1: Fibrin permeation analysis [ Time Frame: Baseline ]
    Darcy constant

  8. WP1: Fibrin permeation analysis [ Time Frame: After 6 weeks of warfarin therapy ]
    Darcy constant

  9. WP1: Fibrin permeation analysis [ Time Frame: Baseline ]
    Fiber mass-length ratio

  10. WP1: Fibrin permeation analysis [ Time Frame: After 6 weeks of warfarin therapy ]
    Fiber mass-length ratio

  11. WP2: Clot formation assessment [ Time Frame: Baseline ]
    Clot formation (lag time)

  12. WP2: Fibrin structure (maximum absorbance) [ Time Frame: Baseline ]
    Fibrin structure (maximum absorbance)

  13. WP2: Fibrin permeation analysis [ Time Frame: Baseline ]
    Flow rates

  14. WP2: Fibrin permeation analysis [ Time Frame: Baseline ]
    Darcy constant

  15. WP2: Fibrin permeation analysis [ Time Frame: Baseline ]
    Fiber mass-length ratio

  16. WP2: Low density lipoprotein fractions [ Time Frame: Baseline ]
    Measure of low density lipoprotein subclass fractions

  17. WP2: Oxidised low density lipoprotein [ Time Frame: Baseline ]
    Measure of oxidised low density lipoprotein in ng/ml

  18. WP3: Clot formation assessment [ Time Frame: Baseline ]
    Clot formation (lag time)

  19. WP3: Clot formation assessment [ Time Frame: After 6 weeks of statin therapy ]
    Clot formation (lag time)

  20. WP3: Fibrin structure (maximum absorbance) [ Time Frame: Baseline ]
    Fibrin structure (maximum absorbance)

  21. WP3: Fibrin structure (maximum absorbance) [ Time Frame: After 6 weeks of statin therapy ]
    Fibrin structure (maximum absorbance)

  22. WP3: Fibrin permeation analysis [ Time Frame: Baseline ]
    Flow rates

  23. WP3: Fibrin permeation analysis [ Time Frame: After 6 weeks of statin therapy ]
    Flow rates

  24. WP3: Fibrin permeation analysis [ Time Frame: Baseline ]
    Darcy constant

  25. WP3: Fibrin permeation analysis [ Time Frame: After 6 weeks of statin therapy ]
    Darcy constant

  26. WP3: Fibrin permeation analysis [ Time Frame: Baseline ]
    Fiber mass-length ratio

  27. WP3: Fibrin permeation analysis [ Time Frame: After 6 weeks of statin therapy ]
    Fiber mass-length ratio

  28. WP3: Low density lipoprotein fractions [ Time Frame: Baseline ]
    Measure of low density lipoprotein subclass fractions

  29. WP3: Low density lipoprotein fractions [ Time Frame: After 6 weeks of statin therapy ]
    Measure of low density lipoprotein subclass fractions

  30. WP3: Oxidised low density lipoprotein [ Time Frame: Baseline ]
    Measure of oxidised low density lipoprotein in ng/ml

  31. WP3: Oxidised low density lipoprotein [ Time Frame: After 6 weeks of statin therapy ]
    Measure of oxidised low density lipoprotein in ng/ml


Secondary Outcome Measures :
  1. WP2: Scanning electron microscopy [ Time Frame: Baseline ]
    Qualitative assessment of fibril indices



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Sampling Method:   Non-Probability Sample
Study Population
Participants will be recruited from the hospital and specialist clinics in the community
Criteria

Inclusion Criteria:

WP1:

  • Diagnosed atrial fibrillation
  • Not on anticoagulation prior to recruitment
  • Plan to commence warfarin therapy
  • Informed consent obtained

WP2:

  • Taking stable doses of warfarin with target and actual INR of 2-3
  • Informed consent obtained

WP3:

  • Statin-naïve at recruitment
  • Diagnosed atrial fibrillation
  • Taking stable doses of warfarin with target and actual INR of 2-3
  • Estimated glomerular filtration rate of <50 ml/min/1.73m2
  • Informed consent obtained

Exclusion Criteria:

  • Age <18 years
  • Severe mitral stenosis or presence of metallic prosthetic valve
  • Active or recent malignancy (<12 months)
  • Active immunological disease
  • Connective tissue disease
  • Chronic liver disease
  • Recent or chronic infection
  • Chronic inflammatory disease
  • Known haemophilia or thrombophilia
  • Active bleeding
  • Untreated hypothyroidism or hyperthyroidism
  • Recent surgery (<3 months)
  • Familial lipid disorders
  • Concurrent use of steroids
  • Concurrent use of non-vitamin K antagonist oral anticoagulant
  • Dietary supplements known to influence lipids
  • Contraindications/inability/unwillingness to commence warfarin (WP1) or statin (WP3)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04043026


Contacts
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Contact: Wern Yew Ding 0151 794 9020 wding@nhs.net

Sponsors and Collaborators
University of Liverpool
Liverpool Centre for Cardiovascular Science
Liverpool Heart and Chest Hospital NHS Foundation Trust
Liverpool John Moores University
University of Leeds
Investigators
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Principal Investigator: Wern Yew Ding University of Liverpool

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Responsible Party: Wern Yew Ding, Clinical Research Fellow, University of Liverpool
ClinicalTrials.gov Identifier: NCT04043026     History of Changes
Other Study ID Numbers: UoL001456 - 4843
First Posted: August 2, 2019    Key Record Dates
Last Update Posted: August 12, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Wern Yew Ding, University of Liverpool:
Anticoagulation
Clot structure and function
Lipoproteins
Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency, Chronic
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Urologic Diseases
Renal Insufficiency
Warfarin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Lipid Regulating Agents
Anticoagulants