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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 : September 27, 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

Tracking Information
First Submitted Date July 26, 2019
First Posted Date August 2, 2019
Last Update Posted Date September 27, 2019
Estimated Study Start Date October 1, 2019
Estimated Primary Completion Date August 2, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 31, 2019)
  • WP1: Clot formation assessment [ Time Frame: Baseline ]
    Clot formation (lag time)
  • WP1: Clot formation assessment [ Time Frame: After 6 weeks of warfarin therapy ]
    Clot formation (lag time)
  • WP1: Fibrin structure (maximum absorbance) [ Time Frame: Baseline ]
    Fibrin structure (maximum absorbance)
  • WP1: Fibrin structure (maximum absorbance) [ Time Frame: After 6 weeks of warfarin therapy ]
    Fibrin structure (maximum absorbance)
  • WP1: Fibrin permeation analysis [ Time Frame: Baseline ]
    Flow rates
  • WP1: Fibrin permeation analysis [ Time Frame: After 6 weeks of warfarin therapy ]
    Flow rates
  • WP1: Fibrin permeation analysis [ Time Frame: Baseline ]
    Darcy constant
  • WP1: Fibrin permeation analysis [ Time Frame: After 6 weeks of warfarin therapy ]
    Darcy constant
  • WP1: Fibrin permeation analysis [ Time Frame: Baseline ]
    Fiber mass-length ratio
  • WP1: Fibrin permeation analysis [ Time Frame: After 6 weeks of warfarin therapy ]
    Fiber mass-length ratio
  • WP2: Clot formation assessment [ Time Frame: Baseline ]
    Clot formation (lag time)
  • WP2: Fibrin structure (maximum absorbance) [ Time Frame: Baseline ]
    Fibrin structure (maximum absorbance)
  • WP2: Fibrin permeation analysis [ Time Frame: Baseline ]
    Flow rates
  • WP2: Fibrin permeation analysis [ Time Frame: Baseline ]
    Darcy constant
  • WP2: Fibrin permeation analysis [ Time Frame: Baseline ]
    Fiber mass-length ratio
  • WP2: Low density lipoprotein fractions [ Time Frame: Baseline ]
    Measure of low density lipoprotein subclass fractions
  • WP2: Oxidised low density lipoprotein [ Time Frame: Baseline ]
    Measure of oxidised low density lipoprotein in ng/ml
  • WP3: Clot formation assessment [ Time Frame: Baseline ]
    Clot formation (lag time)
  • WP3: Clot formation assessment [ Time Frame: After 6 weeks of statin therapy ]
    Clot formation (lag time)
  • WP3: Fibrin structure (maximum absorbance) [ Time Frame: Baseline ]
    Fibrin structure (maximum absorbance)
  • WP3: Fibrin structure (maximum absorbance) [ Time Frame: After 6 weeks of statin therapy ]
    Fibrin structure (maximum absorbance)
  • WP3: Fibrin permeation analysis [ Time Frame: Baseline ]
    Flow rates
  • WP3: Fibrin permeation analysis [ Time Frame: After 6 weeks of statin therapy ]
    Flow rates
  • WP3: Fibrin permeation analysis [ Time Frame: Baseline ]
    Darcy constant
  • WP3: Fibrin permeation analysis [ Time Frame: After 6 weeks of statin therapy ]
    Darcy constant
  • WP3: Fibrin permeation analysis [ Time Frame: Baseline ]
    Fiber mass-length ratio
  • WP3: Fibrin permeation analysis [ Time Frame: After 6 weeks of statin therapy ]
    Fiber mass-length ratio
  • WP3: Low density lipoprotein fractions [ Time Frame: Baseline ]
    Measure of low density lipoprotein subclass fractions
  • WP3: Low density lipoprotein fractions [ Time Frame: After 6 weeks of statin therapy ]
    Measure of low density lipoprotein subclass fractions
  • WP3: Oxidised low density lipoprotein [ Time Frame: Baseline ]
    Measure of oxidised low density lipoprotein in ng/ml
  • WP3: Oxidised low density lipoprotein [ Time Frame: After 6 weeks of statin therapy ]
    Measure of oxidised low density lipoprotein in ng/ml
Original Primary Outcome Measures Same as current
Change History Complete list of historical versions of study NCT04043026 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: July 31, 2019)
WP2: Scanning electron microscopy [ Time Frame: Baseline ]
Qualitative assessment of fibril indices
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title The Effects of Renal Function and Atrial Fibrillation on Lipoproteins and Clot Structure/Function
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
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.
Detailed Description Not Provided
Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Participants will be recruited from the hospital and specialist clinics in the community
Condition
  • Atrial Fibrillation
  • Chronic Kidney Diseases
Intervention
  • Drug: Warfarin
    INR-dependent dosage
  • Drug: Statin
    Any statin therapy acceptable
Study Groups/Cohorts
  • 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
    Intervention: Drug: Warfarin
  • 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
    Intervention: Drug: Warfarin
  • WP2: Group 1 - AF + CKD
    Participants with atrial fibrillation (AF) and chronic kidney disease (CKD) who are on stable doses of warfarin
    Intervention: Drug: Warfarin
  • WP2: Group 2 - AF + no CKD
    Participants with atrial fibrillation (AF) and no chronic kidney disease (CKD) who are on stable doses of warfarin
    Intervention: Drug: Warfarin
  • WP2: Group 3 - no AF + CKD
    Participants with no atrial fibrillation (AF) and chronic kidney disease (CKD) who are on stable doses of warfarin
    Intervention: Drug: Warfarin
  • 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
    Intervention: Drug: Warfarin
  • 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
    Interventions:
    • Drug: Warfarin
    • Drug: Statin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Not yet recruiting
Estimated Enrollment
 (submitted: July 31, 2019)
156
Original Estimated Enrollment Same as current
Estimated Study Completion Date August 2, 2022
Estimated Primary Completion Date August 2, 2022   (Final data collection date for primary outcome measure)
Eligibility 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)
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers Not Provided
Contacts
Contact: Wern Yew Ding 0151 794 9020 wding@nhs.net
Listed Location Countries Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number NCT04043026
Other Study ID Numbers UoL001456 - 4843
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Wern Yew Ding, University of Liverpool
Study Sponsor University of Liverpool
Collaborators
  • Liverpool Centre for Cardiovascular Science
  • Liverpool Heart and Chest Hospital NHS Foundation Trust
  • Liverpool John Moores University
  • University of Leeds
Investigators
Principal Investigator: Wern Yew Ding University of Liverpool
PRS Account University of Liverpool
Verification Date September 2019