The HALT Biomarker Study

NCT04552275 | Recruiting Phase 1

• 1 other identifier: 2020P001793
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 3

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.

Conditions

Aortic Stenosis; Hypo-attenuated Leaflet Thickening; Bioprosthetic Valve Degeneration

Outcome Measures

Primary Outcomes (2)

• Derivation of the panel of circulating proteins indicative of HALT

  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.

  6 months

• Establish the rate at which these characteristics indicative of future HALT

  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.

  6 months

Secondary Outcomes (1)

• Cross-validation of the panel of circulating proteins indicative of HALT

  6 months

Study Arms (2)

HALT Cohort

OTHER

Patients who develop HALT

Diagnostic Test: Proteomics Analysis

Control Group

OTHER

Patients who do not develop HALT

Diagnostic Test: Proteomics Analysis

Interventions

Proteomics Analysis DIAGNOSTIC_TEST

Determine a panel of circulating proteins that discriminates between patients with and without Hypo-Attenuated Leaflet Thickening (HALT)

Control Group; HALT Cohort

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Medtronic: collaborator
• Catholic Medical Center: collaborator
• Minneapolis Heart Institute: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Minneapolis Heart Institute

Minneapolis, Minnesota, 55407, United States

NOT YET RECRUITING

Catholic Medical Center

Manchester, New Hampshire, 03103, United States

RECRUITING

MeSH Terms

Conditions

Aortic Valve Stenosis

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Central Study Contacts

Roukoz Abou Karam

CONTACT

raboukaram@mgh.harvard.edu

Paris J Jamiel, BS

CONTACT

(617) 726-0996; pjamiel@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Interventional Cardiology Research

Study Record Dates

• First Submitted: August 28, 2020
• First Posted: September 17, 2020
• Study Start: June 22, 2020
• Primary Completion (Estimated): June 22, 2030
• Study Completion (Estimated): June 22, 2035
• Last Updated: November 10, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)