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Targeted Testing for ATTR Among Aortic Stenosis Patients-Pilot

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ClinicalTrials.gov Identifier: NCT04363294
Recruitment Status : Withdrawn (grant was not approved, no subjects enrolled)
First Posted : April 27, 2020
Last Update Posted : March 23, 2021
Sponsor:
Collaborator:
Mid America Heart Institute
Information provided by (Responsible Party):
Anthony Bavry, University of Texas Southwestern Medical Center

Brief Summary:

Our ultimate goal is to design a multi-center randomized trial to test the hypothesis that targeted testing for transthyretin cardiac amyloid (ATTR) will improve survival and health status among aortic stenosis patients who undergo transcatheter aortic valve replacement (TAVR). The hypothesis of this pilot study is to evaluate if invasive cardiac hemodynamics obtained after TAVR, by using the AortoVentricular index (AVi), can be used as a novel test to help identify participants with ATTR.

Aim 1. To determine if an abnormal AVi value can identify ATTR among aortic stenosis patients undergoing TAVR.

Aim 2. To determine if s' from echocardiography plus AVi can enhance the prediction of ATTR among aortic stenosis patients undergoing TAVR.

Aim 3. To design a pilot trial to improve patient outcomes after TAVR by targeted testing for ATTR.


Condition or disease Intervention/treatment Phase
Aortic Valve Stenosis Cardiac Amyloidosis Diagnostic Test: PYP scan Not Applicable

Detailed Description:

Aim 1. To determine if an abnormal AVi value can identify ATTR among aortic stenosis patients undergoing TAVR. Patients undergoing TAVR for symptomatic severe aortic stenosis, with pre-TAVR echocardiography and post-implantation invasive hemodynamic assessment are eligible for study participation. The AVi will be recorded from post-implantation invasive hemodynamic assessment. Participants will undergo bone scintigraphy (99mTc-pyrophosphate Planar/SPECT imaging) within 28 days after TAVR. Participants with abnormal bone scintigraphy require evaluation for a monoclonal protein with blood/urine laboratory testing, and possible tissue biopsy/Hematology consultation to exclude light-chain amyloidosis. Participants who are ATTR positive will receive comprehensive heart failure management and possible genetic testing to evaluate for mutated ATTR. The prevalence of ATTR will be reported among participants with AVi <0.5 versus ≥0.5 mm Hg/beats per minute. Test performance of AVi to predict ATTR will be reported.

Aim 2. To determine if s' obtained from echocardiography tissue Doppler imaging plus AVi can enhance the prediction of ATTR among aortic stenosis patients undergoing TAVR. The s' will be recorded from pre-TAVR tissue Doppler imaging of the mitral annulus. The prevalence of ATTR will be reported among participants with both s' ≤6 cm/second and AVi <0.5 mm Hg/beats per minute versus s' >6 cm/second and AVi <0.5 mm Hg/beats per minute.

Aim 3. To design a pilot trial to improve patient outcomes after TAVR by targeted testing for ATTR. The change in Kansas City Cardiomyopathy Questionnaire-12 from baseline to 12-months and survival with reasonable quality of life at 12-months will be reported among participants who are ATTR positive vs. ATTR negative.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Participants undergoing TAVR for symptomatic severe aortic stenosis, with pre-TAVR echocardiography and post-implantation invasive hemodynamic assessment are eligible for study participation. The AVi will be recorded from post-implantation invasive hemodynamic assessment. Participants will undergo bone scintigraphy (99mTc-pyrophosphate Planar/SPECT imaging) within 28 days after TAVR. Participants with abnormal bone scintigraphy require evaluation for a monoclonal protein with blood/urine laboratory testing, and possible tissue biopsy/Hematology consultation to exclude light-chain amyloidosis. Participants who are ATTR positive will receive comprehensive heart failure management and possible genetic testing to evaluate for mutated ATTR.
Masking: None (Open Label)
Primary Purpose: Screening
Official Title: Targeted Testing for Transthyretin Cardiac Amyloid Among Aortic Stenosis Patients-Pilot
Estimated Study Start Date : March 2022
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : August 2023


Arm Intervention/treatment
Participants
Patients who had TAVR and underwent evaluation for ATTR with PYP scan
Diagnostic Test: PYP scan
99mTc-labeled pyrophosphate
Other Name: Bone scan




Primary Outcome Measures :
  1. Prevalence ATTR with AVi <0.5 [ Time Frame: Within 28 days after TAVR when bone scan completed ]
    Prevalence of ATTR among participants with AVi <0.5 mm Hg/beats per minute

  2. Prevalence ATTR with AVi ≥0.5 [ Time Frame: Within 28 days after TAVR when bone scan completed ]
    Prevalence of ATTR among participants with AVi ≥0.5 mm Hg/beats per minute


Secondary Outcome Measures :
  1. Sensitivity AVi [ Time Frame: Within 28 days after TAVR when bone scan completed ]
    Sensitivity of AVi <0.5 mm Hg/beats per minute

  2. Specificity AVi [ Time Frame: Within 28 days after TAVR when bone scan completed ]
    Specificity of AVi ≥0.5 mm Hg/beats per minute

  3. Positive predictive value AVi [ Time Frame: Within 28 days after TAVR when bone scan completed ]
    Positive predictive value of AVi <0.5 at predicting ATTR

  4. Negative predictive value AVi [ Time Frame: Within 28 days after TAVR when bone scan completed ]
    Negative predictive value of AVi ≥0.5 at ruling out ATTR


Other Outcome Measures:
  1. Prevalence ATTR with s'<6 plus AVi <0.5 [ Time Frame: Within 28 days after TAVR when bone scan completed ]
    Prevalence of ATTR among participants with both s'<6 and AVi <0.5 mm Hg/beats per minute

  2. Prevalence ATTR with s'≥6 plus AVi <0.5 [ Time Frame: Within 28 days after TAVR when bone scan completed ]
    Prevalence of ATTR among participants with both s'≥6 and AVi <0.5 mm Hg/beats per minute

  3. KCCQ-12 [ Time Frame: 1 year after TAVR ]
    Kansas City Cardiomyopathy Questionnaire(KCCQ) - a shortened 12 question version of the 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.

  4. Favorable outcome [ Time Frame: 1 year after TAVR ]
    Proportion of subjects who are alive with reasonable quality of life. Reasonable quality of life is defined as KCCQ-12 ≥60 without any meaningful worsening (decrease in KCCQ-12 summary score ≥10).



Information from the National Library of Medicine

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Ages Eligible for Study:   75 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Successful implantation of a transcatheter heart valve with a commercially available valve (i.e. Sapien 3, Sapien Ultra, Evolut R, Evolut Pro, Evolut Pro+, or Lotus Edge) for native or bioprosthetic aortic stenosis
  • Pre-implantation echocardiography with tissue Doppler imaging, if feasible
  • Post-implantation invasive cardiac hemodynamics

Exclusion Criteria:

  • Age <75 years
  • Moderate to severe paravalvular aortic regurgitation on post-operative echocardiography

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): NCT04363294


Sponsors and Collaborators
University of Texas Southwestern Medical Center
Mid America Heart Institute
Investigators
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Principal Investigator: Anthony A Bavry, MD MPH UT Southwestern Medical Center
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Responsible Party: Anthony Bavry, Professor of Medicine, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT04363294    
Other Study ID Numbers: STU-2020-0386
First Posted: April 27, 2020    Key Record Dates
Last Update Posted: March 23, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The primary investigator will upload de-identified individual data after study results have been published
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Data will become available after study results have been published
Access Criteria: The primary investigator will upload study protocol, statistical analysis plan, informed consent form, and clinical study report after study results have been published

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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 Anthony Bavry, University of Texas Southwestern Medical Center:
aortic stenosis
transthyretin cardiac amyloid
transcatheter aortic valve replacement
AortoVentricular index
ATTR
TAVR
AVi
invasive cardiac hemodynamics
Additional relevant MeSH terms:
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Aortic Valve Stenosis
Amyloidosis
Constriction, Pathologic
Pathological Conditions, Anatomical
Proteostasis Deficiencies
Metabolic Diseases
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction