The HALT Biomarker Study

Mass General Brigham

Status and phase: Enrolling; Phase 1

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

Treatments: Diagnostic Test: Proteomics Analysis

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04552275

2020P001793

Details and patient eligibility

About

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.

Enrollment: 300 estimated patients

Sex: All

Ages: 65+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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300 participants in 2 patient groups

HALT Cohort

Other group

Description:

Patients who develop HALT

Treatment:

Diagnostic Test: Proteomics Analysis

Control Group

Other group

Description:

Patients who do not develop HALT

Treatment:

Diagnostic Test: Proteomics Analysis