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The HALT Biomarker Study (HALT)

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ClinicalTrials.gov Identifier: NCT04552275
Recruitment Status : Recruiting
First Posted : September 17, 2020
Last Update Posted : November 10, 2021
Sponsor:
Collaborators:
Medtronic
Catholic Medical Center
Minneapolis Heart Institute
Information provided by (Responsible Party):
Sammy Elmariah, Massachusetts General Hospital

Study Description
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Brief Summary:

The purpose of the HALT Biomarkers study are to identify a panel of circulating proteins that discriminates between patients with and without Hypo-Attenuated Leaflet Thickening (HALT) and can be used to supplement the diagnosis of HALT; to characterize changes in circulating proteins after treatment of HALT with systemic anticoagulation; and to identify circulating proteins that predict the occurrence of HALT.

The study population will be adult patients undergoing transfemoral transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS) or bioprosthetic valve degeneration. Enrollment will continue until 30 patients with HALT are identified for completion of phase 1. Based on a HALT incidence rate of 10%, we anticipate enrolling 300 patients.

Patients are enrolled prior to undergoing transfemoral TAVR. Blood samples, clinical data and echocardiograms will be collected at the following timepoints: baseline (pre-TAVR, T0), post-TAVR (pre-discharge, T1), 30-day follow-up (window 3-9 weeks, T2), and 6-month follow-up (T3). Cardiac 4D CT will be performed at the 30-day follow-up visit to screen for the occurrence of HALT.

Patients with HALT will be treated with systemic anticoagulation for 5-6 months, at which point a follow-up CT scan and blood sample will be obtained. Control subjects will also undergo a 6-month study visit with blood sample collection. The study will be conducted within two phases. Phase 1 will serve as a derivation / discovery study in which candidate protein biomarkers of HALT will be identified.

Once this is successfully completed, a second cohort will be enrolled within phase 2. Phase 2 will be performed under the auspices a future contract or amendment and will seek to cross-validate the initial study findings.


Condition or disease Intervention/treatment Phase
Aortic Stenosis Hypo-attenuated Leaflet Thickening Bioprosthetic Valve Degeneration Diagnostic Test: Proteomics Analysis Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Circulating Biomarkers of Hypo-Attenuated Leaflet Thickening After Transcatheter Aortic Valve Replacement
Actual Study Start Date : June 22, 2020
Estimated Primary Completion Date : June 22, 2030
Estimated Study Completion Date : June 22, 2035

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
HALT Cohort
Patients who develop HALT
 Diagnostic Test: Proteomics Analysis
Determine a panel of circulating proteins that discriminates between patients with and without Hypo-Attenuated Leaflet Thickening (HALT)
Control Group
Patients who do not develop HALT
 Diagnostic Test: Proteomics Analysis
Determine a panel of circulating proteins that discriminates between patients with and without Hypo-Attenuated Leaflet Thickening (HALT)


Outcome Measures
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Primary Outcome Measures :
  1. Derivation of the panel of circulating proteins indicative of HALT [ Time Frame: 6 months ]
    1. Establish the incidence of similar proteomic profiles and the rate to which the profile occurs in TAVR recipients with HALT via a high-throughput precision proteomics platform which utilizes the proximity extension assay (PEA). PEA merges a dual-recognition antibody-based immunoassay with quantitative real-time PCR that allows for the simultaneous quantification of 92 proteins. We will focus on the 5 highest yield panels for the current investigation: cardiovascular II, cardiovascular III, cardiometabolic, inflammation, and oncology II panels. These panels will allow for the assessment of 460 circulating proteins.

  2. Establish the rate at which these characteristics indicative of future HALT [ Time Frame: 6 months ]
    Using data analysis of baseline patient characteristics to establish the rate that they are indicative of future HALT in patients with aortic stenosis. The sampling frame assumes the sequencing of 460 proteins; a 5% False Discovery Rate; a 10% prognostic prevalence; a minimum fold change of 2; and a normalization ratio of 1.


Secondary Outcome Measures :
  1. Cross-validation of the panel of circulating proteins indicative of HALT [ Time Frame: 6 months ]
    3. Using 20 matched pairs of subjects with and without HALT, the derivation of the HALT indicative panel of circulating proteins gathered through PEA will be cross-validated using data analysis to establish the rate to which the panel is present in both cohorts. This rate will be used to determine if the proteomic profile of a patient can be used as a diagnostic test for the presence of HALT.


Eligibility Criteria
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Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age > 65 years
  2. Subject with severe native AS or severe bioprosthetic valve degeneration
  3. Subject undergoing transfemoral TAVR using a Medtronic Evolut R, Evolut Pro or Evolut Pro+ transcatheter heart valve

Exclusion Criteria:

  1. Chronic anticoagulation therapy
  2. Contraindication to systemic oral anticoagulation therapy
  3. Chronic kidney disease with EGFR<30 ml/min
  4. Bleeding diathesis or known coagulopathy
  5. Hypercoagulable state
  6. Life-expectancy <12 months due to other medical conditions (e.g., malignancy, severe Alzheimer's disease, etc.)
  7. The patient is currently participating in another investigational device or drug study that has not reached its primary objective/endpoint
  8. Pregnant, lactating, or planning pregnancy within next 12 months
Contacts and Locations
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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): NCT04552275


Contacts
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Contact: Roukoz Abou Karam raboukaram@mgh.harvard.edu
Contact: Paris J Jamiel, BS (617) 726-0996 pjamiel@mgh.harvard.edu

Locations
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United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact       SELMARIAH@mgh.harvard.edu   
Principal Investigator: Sammy Elmariah, MD         
United States, Minnesota
Minneapolis Heart Institute Not yet recruiting
Minneapolis, Minnesota, United States, 55407
Contact       Santiago.Garcia@allina.com   
Principal Investigator: Santiago Garcia, MD         
United States, New Hampshire
Catholic Medical Center Recruiting
Manchester, New Hampshire, United States, 03103
Contact       fahad.gilani@cmc-nh.org   
Principal Investigator: Fahad S Gilani         
Sponsors and Collaborators
Massachusetts General Hospital
Medtronic
Catholic Medical Center
Minneapolis Heart Institute
More Information
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Responsible Party: Sammy Elmariah, Director, Interventional Cardiology Research, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT04552275    
Other Study ID Numbers: 2020P001793
First Posted: September 17, 2020    Key Record Dates
Last Update Posted: November 10, 2021
Last Verified: November 2021
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
Additional relevant MeSH terms:
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Aortic Valve Stenosis
Aortic Valve Disease
Heart Valve Diseases
 Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction