Acute Kidney Injury Genomics and Biomarkers in TAVR Study

• ClinicalTrials.gov Identifier: NCT02791880
• Recruitment Status: Active, not recruiting
• First Posted: June 7, 2016
• Last Update Posted: June 1, 2022
• Sponsor: University of Texas Southwestern Medical Center
• Information provided by (Responsible Party): Amanda A Fox, MD, MPH, University of Texas Southwestern Medical Center

Study Description

Brief Summary:

In the last decade, transcatheter aortic valve replacement (TAVR) has become an increasingly utilized alternative procedure for replacing a stenotic aortic valve. This study collects clinical information, DNA, blood and urine samples (throughout procedural hospitalization) in order to investigate the incidence of acute kidney injury (AKI) in patients undergoing TAVR and to identify key clinical and procedural predictors of AKI. This study seeks to identify blood and urine biomarkers that can be used for early detection of AKI around the time of the procedure. The study seeks to assess for novel genetic variants associated with development of AKI after TAVR. Finally the study seeks to assess for novel genetic variants and biomarkers that are associated with adverse cardiovascular events after TAVR and to further explore how these events may inter-relate with acute kidney injury.

Condition or disease	Intervention/treatment
Acute Kidney Injury; Renal Insufficiency, Chronic; Heart Failure; Myocardial Infarction; Arrhythmias, Cardiac; Stroke	Procedure: Transcatheter Aortic Valve Replacement

Detailed Description:

This study enrolls patients who have aortic stenosis who undergo TAVR at the University of Texas Southwestern Medical Center University Hospital. Development of post-TAVR AKI defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) SCr based criteria will be ascertained. Patients will be followed during primary hospitalization and during the 5 years following TAVR for adverse kidney outcomes as well as potentially related adverse cardiovascular outcomes. Clinical and procedural data is collected for each study patient. All subjects will have paired blood and urine collection done pre-TAVR, 6 hours after aortic valve prosthesis deployment, and on post-procedure days 1 and 2. Subjects who develop AKI will also have paired blood and urine samples collected on days 3, 4 and 5. Patients receive follow-up questionnaires by mail or email asking about hospitalizations as well as visits to cardiology, nephrology and primary care physicians. Questionnaires will also ask about health-related quality of life using validated study questionnaires. Patient follow-up will occur at regular intervals until 5 years after TAVR procedure.

Study Design

• Study Type: Observational
• Estimated Enrollment: 3000 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Genomic and Biomarker Predictors of Acute Kidney Injury and Other Post-Procedural Outcomes Following Transcatheter Aortic Valve Replacement
• Actual Study Start Date: October 25, 2016
• Estimated Primary Completion Date: March 31, 2031
• Estimated Study Completion Date: March 31, 2031

Groups and Cohorts

Group/Cohort	Intervention/treatment
TAVR patients; The group of interest is the patient population with aortic stenosis who are undergoing transcatheter aortic valve replacement (TAVR)	Procedure: Transcatheter Aortic Valve Replacement; The investigators will collect blood and urine samples from patients with aortic stenosis who are undergoing transcatheter aortic valve replacement.

Outcome Measures

Primary Outcome Measures :

1. Acute Kidney Injury using KDIGO criteria [ Time Frame: Day of procedure to post procedure day 5 ]
   Data will be collected from electronic medical records; data points to be collected for this measurement include serum creatinine

Secondary Outcome Measures :

1. Chronic renal insufficiency (i.e. number of patients that will have received a diagnosis of chronic renal insufficiency) [ Time Frame: Day of procedure to year 5 ]
   Chronic renal insufficiency is defined as patient having impaired renal function (albumin/creatinine ratio >/= 300 mg/g and eGFR <60 mL/min/1.73^2).
2. Heart failure per NYHA class II, III, IV [ Time Frame: Day of procedure to year 5 ]
   This will be measured in accordance to New York Heart Association Guidelines.
3. Presence of Arrhythmia (i.e. number of patients who develop an arrhythmia from postoperative day 0 to 5 years). [ Time Frame: Day of procedure to year 5 ]
   Data will be collected from electronic medical records; data points to be collected for this measurement include post-procedural EKG reports and progress notes.
4. Myocardial Infarction (i.e. number of participants who develop a MI during postoperative day 0 to year 5) [ Time Frame: Day of procedure to year 5 ]
   Data will be collected from electronic medical records; data points to be collected for this measurement include post-procedural EKG reports, cardiac enzyme values, progress notes, and cardiac catheterization reports.
5. Cerebrovascular accident (i.e. number of participants who develop transient ischemic attack or permanent stroke during postoperative day 0 up to 5 years) [ Time Frame: Day of procedure to year 5 ]
   Data will be collected from electronic medical records; data points to be collected for this measurement include post procedural imaging data and progress notes.
6. Vascular complications (i.e. number of participants who develop arterial injury, dissection, limb ischemia during postoperative day 0 up to year 5) [ Time Frame: Day of procedure to year 5 ]
   Data will be collected from electronic medical records; data points to be collected for this measurement include post procedural imaging data, progress notes and operative reports.
7. Need for dialysis (e.g. number of participants who undergo post-procedural dialysis) [ Time Frame: Day of procedure to year 5 ]
   Data will be collected from electronic medical records; data points to be collected for this measurement include progress notes, and consultation notes.
8. Mortality (i.e. number of participants who are deceased during postoperative day 0 up to year 5) [ Time Frame: Day of procedure to year 5 ]
   Data will be collected from electronic medical records; data points to be collected for this measurement include progress notes and death notes.
9. KCCQ Quality of Life Survey [ Time Frame: Administered once prior to the procedure and 1 month to 5 years after hospital discharge ]
   The Kansas City Cardiomyopathy Questionnaire (KCCQ Short Form) is a health-related quality of life measure for heart failure.
10. SAQ Quality of Life Survey [ Time Frame: Administered once prior to the procedure and 1 month to 5 years after hospital discharge ]
    The Seattle Angina Questionnaire (SAQ Short Form) is a health-related quality of life measure for coronary artery disease.
11. SF12 Quality of Life Survey [ Time Frame: Administered once prior to the procedure and 1 month to 5 years after hospital discharge ]
    12-item short form Health survey (SF12) is a health-related quality of life measure of functional health and well-being from the patient's point of view.

Biospecimen Retention:   Samples With DNA

DNA collected before procedure. Paired urine, serum, and plasma samples collected before valve replacement, six hours after valve replacement, and post-procedure days 1 and 2. Additional samples are collected on post-procedure days 3, 4 and 5 if the patient develops acute kidney injury after the procedure.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Subjects will be enrolled from the population of patients with aortic stenosis undergoing TAVR. Enrollment will likely occur over a 15 year time period to reach target enrollment. A total of 3,000 subjects are presently targeted for enrollment at University of Texas Southwestern University Hospitals and Parkland Health and Hospital Systems.

Criteria

Inclusion criteria: Subjects are eligible to participate if they are undergoing TAVR for aortic stenosis at the University of Texas Southwestern Medical Center.

Exclusion Criteria:

1. The patient cannot or will not provide informed consent.
2. The patient is aged less than 18 years.
3. The patient's pre-procedural hematocrit is less than 25%.
4. The patient has known human immunodeficiency virus infection
5. The patient has known hepatitis C that has not been treated with antiviral medications
6. In the opinion of the principal investigator, the patient will be unlikely to complete long-term follow up for medical or social reasons (this includes transient patients and patients who have no fixed address).

Contacts and Locations

Locations

United States, Texas

Parkland Health & Hospital Systems

Dallas, Texas, United States, 75235

University of Texas Southwestern Medical Center

Dallas, Texas, United States, 75390

William J. Clements University Hospital

Dallas, Texas, United States, 75390

Sponsors and Collaborators

University of Texas Southwestern Medical Center

Investigators

• Principal Investigator: Amanda A Fox, MD, MPH; University of Texas Southwestern Medical Center

More Information

• Responsible Party: Amanda A Fox, MD, MPH, Professor of Anesthesiology, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT02791880
• Other Study ID Numbers: STU 112015-015
• First Posted: June 7, 2016
• Last Update Posted: June 1, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: There is a possibility that individual participant data and samples will be de-identified and shared with other cohort study investigators for purposes of replicating biomarker and genetic associations with adverse outcomes.
• Supporting Materials: Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• Time Frame: Data will become available at the discretion of the sponsor/Dr. Fox. Once enough data has been gathered and analyzed, and the need or DUA requests from other cohort researchers is received.
• Access Criteria: Data will be collected in REDCap, a data management tool used primarily for research and QI. It is a secure, HIPAA-compliant web application. Content is backed up offsite nightly and hosted in a secure environment maintained by UTSW Information Resources. Other cohort researchers will access survey questionnaires via the secure and confidential REDCap webpage with specific view only access. Patient confidentiality is of paramount importance. Data sent outside of UTSW will be de-identified or coded. The "key" to the code (i.e. patient identifying information) will not be provided to the recipient unless a limited dataset is approved for sharing via a data use agreement between Dr. Fox/UTSW and the recipient scientist/recipient scientist's institution.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Amanda A Fox, MD, MPH, University of Texas Southwestern Medical Center:

acute kidney injury; transcatheter aortic valve replacement; genomics; biomarker

Additional relevant MeSH terms:

Acute Kidney Injury; Renal Insufficiency; Renal Insufficiency, Chronic; Myocardial Infarction; Arrhythmias, Cardiac; Infarction; Wounds and Injuries; Heart Diseases; Cardiovascular Diseases; Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Vascular Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes