The HALT Biomarker Study

Phase 1

Recruiting

• Conditions: Hypo-attenuated Leaflet Thickening; Aortic Stenosis; Bioprosthetic Valve Degeneration
• Interventions: Diagnostic Test: Proteomics Analysis

• Registration Number: NCT04552275
• Lead Sponsor: Massachusetts General Hospital

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-06-22
• Study First Submitted: 2020-08-28
• Study First Submitted QC: 2020-09-11
• Study First Posted: 2020-09-17
• Status Verified: 2021-11
• Last Update Submitted: 2021-11-02
• Last Update Posted: 2021-11-10
• Primary Completion: 2030-06-22
• Study Completion: 2035-06-22

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HALT Cohort	Proteomics Analysis	Patients who develop HALT
Control Group	Proteomics Analysis	Patients who do not develop HALT

Primary Outcome Measures

Name	Time	Method
Derivation of the panel of circulating proteins indicative of HALT	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.
Establish the rate at which these characteristics indicative of future HALT	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

Name	Time	Method
Cross-validation of the panel of circulating proteins indicative of HALT	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.

Trial Locations

Locations (3)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Minneapolis Heart Institute; 🇺🇸 Minneapolis, Minnesota, United States

Catholic Medical Center; 🇺🇸 Manchester, New Hampshire, United States