Aortic StenosisPhase 1HALTNCT04552275
The HALT Biomarker Study
A Phase 1 study testing Proteomics Analysis in people with Aortic Stenosis and Hypo-attenuated Leaflet Thickening, run by Massachusetts General Hospital at 3 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Aortic Stenosis, Hypo-attenuated Leaflet Thickening, Bioprosthetic Valve Degeneration
- What is being tested?
- Proteomics Analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 3 sitesUnited States
- Study dates
- 22 Jun 2020to 22 Jun 2035
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Roukoz Abou Karam contact
United States3 sites, 3 recruiting
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
SELMARIAH@mgh.harvard.edu
Sammy Elmariah, MD
- Recruiting
Catholic Medical Center
Manchester, New Hampshire, 03103
fahad.gilani@cmc-nh.org
Fahad S Gilani
- Not yet recruiting
Minneapolis Heart Institute
Minneapolis, Minnesota, 55407
Santiago.Garcia@allina.com
Santiago Garcia, MD
About this study
Official title: Circulating Biomarkers of Hypo-Attenuated Leaflet Thickening After Transcatheter Aortic Valve Replacement
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.
Read more
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.
- Being tested
- Proteomics Analysis
- Medical subject headings
- Aortic Valve Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Proteomics AnalysisDiagnostic test
Determine a panel of circulating proteins that discriminates between patients with and without Hypo-Attenuated Leaflet Thickening (HALT)
| Study group | Role | What they receive |
|---|---|---|
| HALT Cohort | Other | Patients who develop HALT Receives: Diagnostic Test: Proteomics Analysis |
| Control Group | Other | Patients who do not develop HALT Receives: Diagnostic Test: Proteomics Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Derivation of the panel of circulating proteins indicative of HALT
- 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.
Measured: 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.
Measured: 6 months
Secondary outcomes (1)
Cross-validation of the panel of circulating proteins indicative of HALT
- 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.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2020
- Study start22 Jun 2020
- Primary completion22 Jun 2030 (estimated)
- Study completion22 Jun 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Aortic StenosisStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Medtronic, Catholic Medical Center, Minneapolis Heart Institute
- Responsible party
- Principal investigator, Sammy Elmariah, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04552275
- Sponsor's protocol ID
- 2020P001793
- Acronym
- HALT
- Status last verified
- Nov 2021
- First submitted
- 28 Aug 2020
- Last updated
- 10 Nov 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Circulating Biomarkers of Hypo-Attenuated Leaflet Thickening After Transcatheter Aortic Valve Replacement
- ClinicalTrials.gov ID
- NCT04552275
- Acronym / sponsor ID
- HALT / 2020P001793
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Medtronic, Catholic Medical Center, Minneapolis Heart Institute
- Study start
- 22 Jun 2020 (actual)
- Primary completion
- 22 Jun 2030 (estimated)
- Study completion
- 22 Jun 2035 (estimated)
- First posted
- 17 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HALT Cohort | Other | Diagnostic Test: Proteomics AnalysisPatients who develop HALT |
| Control Group | Other | Diagnostic Test: Proteomics AnalysisPatients who do not develop HALT |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (8 listed)
- Chronic anticoagulation therapy
- Contraindication to systemic oral anticoagulation therapy
- Chronic kidney disease with EGFR<30 ml/min
- Bleeding diathesis or known coagulopathy
- Hypercoagulable state
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Proteomics AnalysisDetermine a panel of circulating proteins that discriminates between patients with and without Hypo-Attenuated Leaflet Thickening (HALT) | Diagnostic test | Control Group, HALT Cohort |
Primary outcome
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.
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.
1 secondary outcome
Cross-validation of the panel of circulating proteins indicative of HALT
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Roukoz Abou Karam contact
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Proteomics Analysis in people with Aortic Stenosis and Hypo-attenuated Leaflet Thickening, run by Massachusetts General Hospital at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Roukoz Abou Karam (raboukaram@mgh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Derivation of the panel of circulating proteins indicative of HALT (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Nov 2021.