Clinical trial NCT04552275: The HALT Biomarker Study
Official title: Circulating Biomarkers of Hypo-Attenuated Leaflet Thickening After Transcatheter Aortic Valve Replacement
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Aortic Stenosis
Hypo-attenuated Leaflet Thickening
Bioprosthetic Valve Degeneration
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Medtronic
name: Catholic Medical Center
name: Minneapolis Heart Institute
First posted: 2020-09-17
Enrollment: 300
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.


Eligibility 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

Primary outcomes:
measure: Derivation of the panel of circulating proteins indicative of HALT
timeFrame: 6 months
measure: Establish the rate at which these characteristics indicative of future HALT
timeFrame: 6 months
Secondary outcomes:
measure: Cross-validation of the panel of circulating proteins indicative of HALT
timeFrame: 6 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute
state: Minnesota
city: Manchester
country: United States
facility: Catholic Medical Center
state: New Hampshire
Study officials:
References: