Heart FailureBIOCRTNCT01949246
Biomarkers to Predict CRT Response in Patients With HF (BIOCRT)
An observational study of Heart Failure, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
The prospective study aims: 1. To determine the role and mechanism of biomarkers for prediction of response to CRT 2. To determine the role of biomarkers and their effect on left ventricular remodeling in patients undergoing CRT. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Heart Failure
- How many people
- 221 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2007to 1 Jan 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Outpatient or inpatient heart failure patients scheduled for CRT implantation
Who may be able to join
- Study participant with an approved indication for a CRT or CRT-D system.
- New York Heart Association (NYHA) Class II, III, or IV Heart Failure unresponsive to drug therapy.
- EF < 35%.
- QRS width > 120 ms.
- Study participant receiving optimal medical therapy including ACE inhibitor or Angiotensin Receptor Blocker (ARB), Beta-Blocker, and Diuretic.
- Study participants with a history of significant congestive decompensation events within the last 12 months.
Who cannot join
- NYHA Class I Heart Failure.
- Co morbidities (e.g., cancer), which may limit lifespan < 6 months.
- Severe aortic stenosis (valve area < 1.0 cm2).
- Study participants that received cardiac surgery or intervention (i.e. coronary artery bypass grafting (CABG), valve surgery, angioplasty, arthrectomy) within the preceding 90 days.
- Study participants with moderate to severe chronic obstructive pulmonary disease (COPD), defined as needing chronic oxygen therapy or recent hospitalization (within 30 days) for COPD flare up.
- Concurrent pregnancy.
- Study participants with primary pulmonary hypertension.
- Study participants on continuous or intermittent infusion therapy for heart failure.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: Analysis of Circulating Biomarkers in Predicting Response to Cardiac Resynchronization Therapy (CRT) With Biventricular Pacing in Patients With Congestive Heart Failure (BIOCRT)
The prospective study aims:
- To determine the role and mechanism of biomarkers for prediction of response to CRT
- To determine the role of biomarkers and their effect on left ventricular remodeling in patients undergoing CRT.
Read the detailed description
Cardiac resynchronization therapy (CRT) with biventricular pacing has emerged as a novel treatment for congestive heart failure (CHF) not responsive to optimal drug therapy. CRT is associated with significant improvements in hemodynamics and functional status of patients with CHF. The physiologic effect of CRT is achieved via placing electrical leads in the right and left ventricular walls, and synchronizing ventricular contraction. Over time, this leads to ventricular wall reverse remodeling, and sustained improvements in left ventricular ejection fraction (EF).
Currently, the indications for CRT include end-stage heart failure class II-IV with an EF < 35%, and a QRS duration > 120ms. The QRS duration is used as an indicator of the degree of ventricular electromechanical dyssynchrony, however, a growing number of studies have postulated its inability to predict response to therapy. As a result, other measures of mechanical dyssynchrony are being sought to guide therapy. The vast majority of these studies have examined clinical, cardiac, electrocardiographic, and device-specific indices, however, a widely accepted predictor of response to CRT is lacking.
CRT results in electromechanical synchrony, leading to an improved ejection fraction, exercise tolerance, and reduction of symptoms. Although electrical re-synchronization and intra-procedural hemodynamic improvement are achieved after the device is implanted, the sustained clinical improvement is likely due to ventricular reverse remodeling. A major issue with CRT is that approximately a third of patients receiving devices do not achieve improved clinical or functional status, and fail to undergo changes in ventricular geometry, and ventricular remodeling. It remains unknown whether this is due to abnormalities in the factors involved in lead placement or procedural strategies, geometric remodeling, alterations in cardiac energy metabolism, supply of energy (i.e. coronary blood flow), or inappropriate/inadequate microvascular proliferation.
This study will evaluate a series of biochemical markers implicated in pathophysiology of heart failure, in predicting response to CRT with biventricular pacing.
- Conditions
- Heart Failure
- Keywords
- Biomarkers
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| CRT patients | Patients undergoing CRT device implantation | |
| Healthy patients | Healthy controls |
What is being measured
The primary outcome is the main question the study is designed to answer.
MACE
death, HF hospitalization, left ventricular assist device, heart transplant
Measured: 2 years
Secondary outcomes (1)
CRT clinical response
For the definition of a positive response to CRT, patients will be classified according to the HF Clinical Composite Score (CCS). Responders will be defined as those with improved CCS from baseline to 6 month follow-up. Those not meeting this criterion will be considered nonresponders. An outcome panel consisting of two cardiologists will determine the clinical response of each subject based on review of the medical record. If there is disagreement in the assessment of either baseline or follow-up CCS amongst the two cardiologists, a third cardiologist will adjudicate the case.
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 posted24 Sep 2013 (estimated)
- Study startSep 2007
- Primary completion1 Jan 2016
- Study completion1 Jan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 221 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jagmeet Singh, Massachusetts General Hospital
- Investigators
- Jagmeet P Singh, Principal investigator, Massachussetts General HospitalQuynh A Truong, MD MPH, Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01949246
- Sponsor's protocol ID
- 2007P001921
- Acronym
- BIOCRT
- Status last verified
- Sep 2022
- First submitted
- 4 Sep 2013
- Last updated
- 3 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
Truong QA, Januzzi JL, Szymonifka J, Thai WE, Wai B, Lavender Z, Sharma U, Sandoval RM, Grunau ZS, Basnet S, Babatunde A, Ajijola OA, Min JK, Singh JP. Coronary sinus biomarker sampling compared to peripheral venous blood for predicting outcomes in patients with severe heart failure undergoing cardiac resynchronization therapy: the BIOCRT study. Heart Rhythm. 2014 Dec;11(12):2167-75. doi: 10.1016/j.hrthm.2014.07.007. Epub 2014 Jul 8.
PubMed 25014756Ajijola OA, Chatterjee NA, Gonzales MJ, Gornbein J, Liu K, Li D, Paterson DJ, Shivkumar K, Singh JP, Herring N. Coronary Sinus Neuropeptide Y Levels and Adverse Outcomes in Patients With Stable Chronic Heart Failure. JAMA Cardiol. 2020 Mar 1;5(3):318-325. doi: 10.1001/jamacardio.2019.4717.
PubMed 31876927Bakos Z, Chatterjee NC, Reitan C, Singh JP, Borgquist R. Prediction of clinical outcome in patients treated with cardiac resynchronization therapy - the role of NT-ProBNP and a combined response score. BMC Cardiovasc Disord. 2018 Apr 24;18(1):70. doi: 10.1186/s12872-018-0802-8.
PubMed 29699498
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Analysis of Circulating Biomarkers in Predicting Response to Cardiac Resynchronization Therapy (CRT) With Biventricular Pacing in Patients With Congestive Heart Failure (BIOCRT)
- ClinicalTrials.gov ID
- NCT01949246
- Acronym / sponsor ID
- BIOCRT / 2007P001921
- Conditions
- Heart Failure
- Keywords
- Biomarkers
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 221 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- Sep 2007 (actual)
- Primary completion
- 1 Jan 2016 (actual)
- Study completion
- 1 Jan 2016 (actual)
- First posted
- 24 Sep 2013 (estimated)
- 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 prospective study aims:
- To determine the role and mechanism of biomarkers for prediction of response to CRT
- To determine the role of biomarkers and their effect on left ventricular remodeling in patients undergoing CRT.
Detailed description
Cardiac resynchronization therapy (CRT) with biventricular pacing has emerged as a novel treatment for congestive heart failure (CHF) not responsive to optimal drug therapy. CRT is associated with significant improvements in hemodynamics and functional status of patients with CHF. The physiologic effect of CRT is achieved via placing electrical leads in the right and left ventricular walls, and synchronizing ventricular contraction. Over time, this leads to ventricular wall reverse remodeling, and sustained improvements in left ventricular ejection fraction (EF).
Currently, the indications for CRT include end-stage heart failure class II-IV with an EF < 35%, and a QRS duration > 120ms. The QRS duration is used as an indicator of the degree of ventricular electromechanical dyssynchrony, however, a growing number of studies have postulated its inability to predict response to therapy. As a result, other measures of mechanical dyssynchrony are being sought to guide therapy. The vast majority of these studies have examined clinical, cardiac, electrocardiographic, and device-specific indices, however, a widely accepted predictor of response to CRT is lacking.
CRT results in electromechanical synchrony, leading to an improved ejection fraction, exercise tolerance, and reduction of symptoms. Although electrical re-synchronization and intra-procedural hemodynamic improvement are achieved after the device is implanted, the sustained clinical improvement is likely due to ventricular reverse remodeling. A major issue with CRT is that approximately a third of patients receiving devices do not achieve improved clinical or functional status, and fail to undergo changes in ventricular geometry, and ventricular remodeling. It remains unknown whether this is due to abnormalities in the factors involved in lead placement or procedural strategies, geometric remodeling, alterations in cardiac energy metabolism, supply of energy (i.e. coronary blood flow), or inappropriate/inadequate microvascular proliferation.
This study will evaluate a series of biochemical markers implicated in pathophysiology of heart failure, in predicting response to CRT with biventricular pacing.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CRT patients | – | –Patients undergoing CRT device implantation |
| Healthy patients | – | –Healthy controls |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Outpatient or inpatient heart failure patients scheduled for CRT implantation
Key inclusion criteria (6 listed)
- Study participant with an approved indication for a CRT or CRT-D system.
- Study participant receiving optimal medical therapy including ACE inhibitor or Angiotensin Receptor Blocker (ARB), Beta-Blocker, and Diuretic.
- Study participants with a history of significant congestive decompensation events within the last 12 months.
Key exclusion criteria (8 listed)
- NYHA Class I Heart Failure.
- Co morbidities (e.g., cancer), which may limit lifespan < 6 months.
- Severe aortic stenosis (valve area < 1.0 cm2).
- Study participants that received cardiac surgery or intervention (i.e. coronary artery bypass grafting (CABG), valve surgery, angioplasty, arthrectomy) within the preceding 90 days.
- Study participants with moderate to severe chronic obstructive pulmonary disease (COPD), defined as needing chronic oxygen therapy or recent hospitalization (within 30 days) for COPD flare up.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
MACE
Time frame: 2 years
death, HF hospitalization, left ventricular assist device, heart transplant
1 secondary outcome
CRT clinical response
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2022.
- Results publication: PubMed 25014756Truong QA, Januzzi JL, Szymonifka J, Thai WE, Wai B, Lavender Z, Sharma U, Sandoval RM, Grunau ZS, Basnet S, Babatunde A, Ajijola OA, Min JK, Singh JP. Coronary sinus biomarker sampling compared to peripheral venous blood for predicting outcomes in patients with severe heart failure undergoing cardiac resynchronization therapy: the BIOCRT study. Heart Rhythm. 2014 Dec;11(12):2167-75. doi: 10.1016/j.hrthm.2014.07.007. Epub 2014 Jul 8.
- Derived from this study: PubMed 31876927Ajijola OA, Chatterjee NA, Gonzales MJ, Gornbein J, Liu K, Li D, Paterson DJ, Shivkumar K, Singh JP, Herring N. Coronary Sinus Neuropeptide Y Levels and Adverse Outcomes in Patients With Stable Chronic Heart Failure. JAMA Cardiol. 2020 Mar 1;5(3):318-325. doi: 10.1001/jamacardio.2019.4717.
- Derived from this study: PubMed 29699498Bakos Z, Chatterjee NC, Reitan C, Singh JP, Borgquist R. Prediction of clinical outcome in patients treated with cardiac resynchronization therapy - the role of NT-ProBNP and a combined response score. BMC Cardiovasc Disord. 2018 Apr 24;18(1):70. doi: 10.1186/s12872-018-0802-8.
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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. This study is not recruiting at the moment.
Jagmeet P Singh principal investigator
Massachussetts General Hospital
Quynh A Truong, MD MPH principal investigator
Weill Medical College of Cornell University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Heart Failure, run by Massachusetts General Hospital at 1 site 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 6 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: finished, as of the sponsor's last update on 3 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MACE (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01949246, which also lists 3 linked publications.
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 3 Oct 2022.