Congestive Heart FailureHis-SYNCNCT02700425
His Bundle Pacing Versus Coronary Sinus Pacing for Cardiac Resynchronization Therapy
A study testing CRT Pacemaker in people with Congestive Heart Failure, run by University of Chicago at 8 sites in United States.
Trial summary
The goal of this study is to compare the effectiveness of pacing from a physiologic His bundle (HB) lead position versus with the standard coronary sinus (CS) lead position in subjects with heart failure undergoing cardiac resynchronization therapy (CRT). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Congestive Heart Failure
- What is being tested?
- CRT Pacemaker
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 8 sitesUnited States
- Study dates
- 17 May 2016to 31 Jul 2020
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients at least 18 years of age
- LV systolic dysfunction with LVEF ≤ 35%
- Evidence of intraventricular conduction delay with QRS duration > 120 msec
- NYHA Class II, III, and ambulatory Class IV heart failure with either ischemic or nonischemic cardiomyopathy and patients with NYHA Class I symptoms and ischemic cardiomyopathy
- Left ventricular ejection fraction (LVEF) ≤ 35%, sinus rhythm (SR), left bundle-branch block (LBBB) morphology, and QRS duration ≥ 150 msec, and NYHA Class II, III, or ambulatory Class IV patients on goal-directed medical therapy (GDMT) [Class I]
- LVEF ≤ 35%, SR with LBBB with QRS 120-149 msec on GDMT [Class IIa]
Show all 11Show fewer
- LVEF ≤ 35%, SR with non-LBBB with QRS ≥ 150 msec on GDMT [Class IIa]
- LVEF ≤ 35%, in AF if medication or AV nodal ablation will allow near 100% pacing [Class IIa]
- LVEF ≤ 35% undergoing new or replacement device with anticipated >40% ventricular pacing on GDMT [Class IIa]
- LVEF ≤ 30%, ischemic etiology of HF, SR with LBBB ≥ 150 msec and NYHA Class I symptoms on GDMT [Class IIb]
- LVEF ≤ 35%, SR with non-LBBB with QRS 120-149 msec, NYHA Class III/ambulatory Class IV HF on GDMT [Class IIb] LVEF ≤ 35%, SR with non-LBBB with QRS ≥ 150 msec, NYHA Class II HF on GDMT [Class IIb]
Who cannot join
- Existing CRT device
- Inability of patient capacity to provide consent for themselves either due to medical or psychiatric comorbidity
- Pregnancy
- Participation in other trials
- Difficulty with follow-up
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Northwestern University
Chicago, Illinois, 60611
Rush University Medical Center
Chicago, Illinois, 60612
The University of Chicago
Chicago, Illinois, 60637
Indiana University
Indianapolis, Indiana, 46202
The University of California, Los Angeles
Los Angeles, California, 90095
Baptist Health Louisville
Louisville, Kentucky, 40207
Edward Hospital
Naperville, Illinois, 60540
Geisinger Wyoming Valley Medical Center
Wilkes-Barre, Pennsylvania, 18711
About this study
The goal of this study is to compare the effectiveness of pacing from a physiologic His bundle (HB) lead position versus with the standard coronary sinus (CS) lead position in subjects with heart failure undergoing cardiac resynchronization therapy (CRT). While placement of left ventricular leads via the coronary sinus has anatomic limitations, we hypothesis that the achievement of QRS narrowing with His bundle capture will be superior for improving systolic function by echocardiographic indices (ejection fraction and strain) and quality of life and decreased rehospitalization and mortality.
Read the detailed description
This is a randomized, single-blinded study of 40 patients to a strategy of HB pacing versus CS pacing, and remain blinded to their treatment allocation. Both treatment options use standard-of-care, FDA-approved devices. The distinction is only in the allocation toward HB pacing and CS pacing. Treating physicians will be aware of assignment in order to facilitate routine device follow-up. Echocardiographic and electrocardiographic evaluation will also be performed in a blinded manner.
Cross-over is permitted between treatment group allocation if:
- CS lead cannot be placed due to difficult cannulation of the CS, limited branches at the posterolateral or lateral wall, or phrenic nerve capture. These subjects may then cross-over to HB pacing.
- HB pacing subjects may cross-over if HB lead cannot be positioned with adequate stability and reasonable pacing output, or if QRS width does not narrow by at least 20% or to a QRS width of ≤ 130 msec.
Implant procedure will be per routine percutaneous access, as is standard for pacemaker and ICDs. All subjects will receive an FDA-approved cardiac resynchronization therapy pacemaker or defibrillator device, as per standard of care outlined for the subject. In order to facilitate optimal lead placement, arterial access for levo-phase CS angiography and/or LV septal mapping to characterize site of bundle-branch block may also be performed, at the discretion of the implanting physician per his/her standard practice.
Follow-up will be performed at 2 weeks post-implant for incision check and device interrogation as is standard of care. In addition, routine device and clinical follow-up will be scheduled at 1, 3, 6, and 12 months. Electrocardiography (ECG) will be performed pre-implant, prior to hospital discharge, at 3 months, 6 months, and 12 months. Echocardiography will be performed pre-implant and 6 months to evaluate for change in LVEF, chamber dimension, and wall motion with strain imaging as is standard of care in the treatment of patients with advanced heart failure. NYHA functional class and quality of life (utilizing the Kansas City Cardiomyopathy Questionnaire) will be assessed pre-implant and at 6 months.
- Conditions
- Congestive Heart Failure
- Being tested
- CRT Pacemaker
- Keywords
- Wide QRS, Ventricular Dyssynchrony
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CRT PacemakerDevice
Cardiac Resynchronization Therapy (CRT) is the use of a pacemaker with two endocardial leads placed in the right atrium (RA) and right ventricle (RV). The third lead is traditionally placed in a tributary of the coronary sinus (CS) overlying the epicardial surface of the left ventricle (LV). Alternatively, the third lead may be positioned based on mapping of the common His bundle and actively fixed to achieve QRS normalization via direct His bundle capture.
| Study group | Role | What they receive |
|---|---|---|
| His Bundle Pacing | Active comparator | Subjects will be randomized to the HB lead position with their cardiac resynchronization therapy (CRT) pacemaker. HB lead pacing will be performed with the Medtronic SelectSecure™, Model 3830 lead. Delivery of the lead utilizes a deflectable sheath, the Medtronic SelectSite™, Model C304. Both devices are FDA approved for the purpose of HB pacing. It is the only device available which is presently FDA approved for selective HB pacing. Receives: Device: CRT Pacemaker |
| Coronary Sinus Pacing | Active comparator | Subjects will be randomized to the CS lead position with their cardiac resynchronization therapy (CRT) pacemaker. CS lead and CRT device generator selected for implant will be left to the discretion of the operator. Only FDA approved CS leads and CRT generators will be utilized in the study. There are five present manufacturers of CS leads and CRT generators: Biotronik, Boston Scientific, Medtronic, Sorin, and St. Jude Medical. Receives: Device: CRT Pacemaker |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Left Ventricular Ejection Fraction (LVEF)
Change in left ventricular ejection fraction (LVEF) as measured by echocardiography in a blinded core lab.
Measured: baseline and 6 months
Change in QRS Duration
Change in QRS duration as measured by electrocardiography
Measured: baseline and 12 months
Time to First Cardiovascular Hospitalization or Death
Time to first cardiovascular hospitalization or death in months
Measured: Through study completion, an average of 12 months.
Secondary outcomes (4)
New York Heart Association (NYHA) Functional Class Change
New York Heart Association (NYHA) functional class change for baseline, 6 months, and 12 months. NYHA class determines the functional status of the patient. There are classes I-IV. Class I is no symptoms or limitation of physical activity, II is slight limitation of physical activity but comfortable at rest, III marked limitation of physical activity, and IV is unable to carry any physical activity without discomfort, heart failure symptoms at rest, and discomfort increases with any physical activity as described the American Heart Association (AHA).
Measured: baseline, 6 months, and 12 months
Quality of Life Change by Kansas City Questionnaire (KCCQ)
Quality of life change as measured by Kansas City Questionnaire (KCCQ) is a 23-item instrument that is self-administered. KCCQ measures physical function, symptoms (specifically frequency, severity, and recent change), social function, self-efficacy and knowledge, and quality of life. Subscales and Total Score range from minimum of 0-100 (maximum); higher scores show better health status. Developed and validated by Dr. John Spertus,MD of University of Missouri-Kansas City.
Measured: baseline and 12 months
Time to First Cardiovascular Rehospitalization
Time to first cardiovascular rehospitalization in 12 months
Measured: Through study completion, an average of 12 months
Time to First Treated Ventricular Arrhythmia/Ventricular Tachycardia (VT/VF)
Time to first treated ventricular arrhythmia/ventricular tachycardia (VT/VF) in 12 months
Measured: Through study completion, an average of 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2016 (estimated)
- Study start17 May 2016
- Primary completion31 Jul 2020
- Study completion31 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Congestive Heart FailureStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Collaborators
- University of California, Los Angeles, Northwestern University, Rush University Medical Center, Geisinger Clinic, Indiana University, Edward Hospital, Baptist Health, Louisville
- Responsible party
- Sponsor
- Investigators
- Roderick Tung, MD, Principal investigator, University of ChicagoGaurav A. Upadhyay, MD, Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02700425
- Sponsor's protocol ID
- IRB15-1728
- Acronym
- His-SYNC
- Status last verified
- Jul 2021
- First submitted
- 29 Jan 2016
- Last updated
- 5 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Upadhyay GA, Vijayaraman P, Nayak HM, Verma N, Dandamudi G, Sharma PS, Saleem M, Mandrola J, Genovese D, Tung R; His-SYNC Investigators. His Corrective Pacing or Biventricular Pacing for Cardiac Resynchronization in Heart Failure. J Am Coll Cardiol. 2019 Jul 9;74(1):157-159. doi: 10.1016/j.jacc.2019.04.026. Epub 2019 May 9. No abstract available.
PubMed 31078637Upadhyay GA, Vijayaraman P, Nayak HM, Verma N, Dandamudi G, Sharma PS, Saleem M, Mandrola J, Genovese D, Oren JW, Subzposh FA, Aziz Z, Beaser A, Shatz D, Besser S, Lang RM, Trohman RG, Knight BP, Tung R; His-SYNC Investigators. On-treatment comparison between corrective His bundle pacing and biventricular pacing for cardiac resynchronization: A secondary analysis of the His-SYNC Pilot Trial. Heart Rhythm. 2019 Dec;16(12):1797-1807. doi: 10.1016/j.hrthm.2019.05.009. Epub 2019 May 13.
PubMed 31096064
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- His Bundle Pacing Versus Coronary Sinus Pacing for Cardiac Resynchronization Therapy
- ClinicalTrials.gov ID
- NCT02700425
- Acronym / sponsor ID
- His-SYNC / IRB15-1728
- Conditions
- Congestive Heart Failure
- Keywords
- Wide QRS, Ventricular Dyssynchrony
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Collaborators
- University of California, Los Angeles, Northwestern University, Rush University Medical Center, Geisinger Clinic, Indiana University, Edward Hospital, Baptist Health, Louisville
- Study start
- 17 May 2016 (actual)
- Primary completion
- 31 Jul 2020 (actual)
- Study completion
- 31 Jul 2020 (actual)
- First posted
- 7 Mar 2016 (estimated)
- Results
- Posted 10 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this study is to compare the effectiveness of pacing from a physiologic His bundle (HB) lead position versus with the standard coronary sinus (CS) lead position in subjects with heart failure undergoing cardiac resynchronization therapy (CRT). While placement of left ventricular leads via the coronary sinus has anatomic limitations, we hypothesis that the achievement of QRS narrowing with His bundle capture will be superior for improving systolic function by echocardiographic indices (ejection fraction and strain) and quality of life and decreased rehospitalization and mortality.
Detailed description
This is a randomized, single-blinded study of 40 patients to a strategy of HB pacing versus CS pacing, and remain blinded to their treatment allocation. Both treatment options use standard-of-care, FDA-approved devices. The distinction is only in the allocation toward HB pacing and CS pacing. Treating physicians will be aware of assignment in order to facilitate routine device follow-up. Echocardiographic and electrocardiographic evaluation will also be performed in a blinded manner.
Cross-over is permitted between treatment group allocation if:
- CS lead cannot be placed due to difficult cannulation of the CS, limited branches at the posterolateral or lateral wall, or phrenic nerve capture. These subjects may then cross-over to HB pacing.
- HB pacing subjects may cross-over if HB lead cannot be positioned with adequate stability and reasonable pacing output, or if QRS width does not narrow by at least 20% or to a QRS width of ≤ 130 msec.
Implant procedure will be per routine percutaneous access, as is standard for pacemaker and ICDs. All subjects will receive an FDA-approved cardiac resynchronization therapy pacemaker or defibrillator device, as per standard of care outlined for the subject. In order to facilitate optimal lead placement, arterial access for levo-phase CS angiography and/or LV septal mapping to characterize site of bundle-branch block may also be performed, at the discretion of the implanting physician per his/her standard practice.
Follow-up will be performed at 2 weeks post-implant for incision check and device interrogation as is standard of care. In addition, routine device and clinical follow-up will be scheduled at 1, 3, 6, and 12 months. Electrocardiography (ECG) will be performed pre-implant, prior to hospital discharge, at 3 months, 6 months, and 12 months. Echocardiography will be performed pre-implant and 6 months to evaluate for change in LVEF, chamber dimension, and wall motion with strain imaging as is standard of care in the treatment of patients with advanced heart failure. NYHA functional class and quality of life (utilizing the Kansas City Cardiomyopathy Questionnaire) will be assessed pre-implant and at 6 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| His Bundle Pacing | Active comparator | Device: CRT PacemakerSubjects will be randomized to the HB lead position with their cardiac resynchronization therapy (CRT) pacemaker. HB lead pacing will be performed with the Medtronic SelectSecure™, Model 3830 lead. Delivery of the lead utilizes a deflectable sheath, the Medtronic SelectSite™, Model C304. Both devices are FDA approved for the purpose of HB pacing. It is the only device available which is presently FDA approved for selective HB pacing. |
| Coronary Sinus Pacing | Active comparator | Device: CRT PacemakerSubjects will be randomized to the CS lead position with their cardiac resynchronization therapy (CRT) pacemaker. CS lead and CRT device generator selected for implant will be left to the discretion of the operator. Only FDA approved CS leads and CRT generators will be utilized in the study. There are five present manufacturers of CS leads and CRT generators: Biotronik, Boston Scientific, Medtronic, Sorin, and St. Jude Medical. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients at least 18 years of age
- LV systolic dysfunction with LVEF ≤ 35%
- Evidence of intraventricular conduction delay with QRS duration > 120 msec
- NYHA Class II, III, and ambulatory Class IV heart failure with either ischemic or nonischemic cardiomyopathy and patients with NYHA Class I symptoms and ischemic cardiomyopathy
- Left ventricular ejection fraction (LVEF) ≤ 35%, sinus rhythm (SR), left bundle-branch block (LBBB) morphology, and QRS duration ≥ 150 msec, and NYHA Class II, III, or ambulatory Class IV patients on goal-directed medical therapy (GDMT) [Class I]
Key exclusion criteria (5 listed)
- Existing CRT device
- Inability of patient capacity to provide consent for themselves either due to medical or psychiatric comorbidity
- Pregnancy
- Participation in other trials
- Difficulty with follow-up
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 |
|---|---|---|
| CRT PacemakerCardiac Resynchronization Therapy (CRT) is the use of a pacemaker with two endocardial leads placed in the right atrium (RA) and right ventricle (RV). The third lead is traditionally placed in a tributary of the coronary sinus (CS) overlying the epicardial surface of the left ventricle (LV). Alternatively, the third lead may be positioned based on mapping of the common His bundle and actively fixed to achieve QRS normalization via direct His bundle capture. | Device | Coronary Sinus Pacing, His Bundle Pacing |
Primary outcome
Change in Left Ventricular Ejection Fraction (LVEF)
Time frame: baseline and 6 months
Change in left ventricular ejection fraction (LVEF) as measured by echocardiography in a blinded core lab.
Change in QRS Duration
Time frame: baseline and 12 months
Change in QRS duration as measured by electrocardiography
Time to First Cardiovascular Hospitalization or Death
Time frame: Through study completion, an average of 12 months.
Time to first cardiovascular hospitalization or death in months
4 secondary outcomes
New York Heart Association (NYHA) Functional Class Change
Time frame: baseline, 6 months, and 12 months
Quality of Life Change by Kansas City Questionnaire (KCCQ)
Time frame: baseline and 12 months
Time to First Cardiovascular Rehospitalization
Time frame: Through study completion, an average of 12 months
Time to First Treated Ventricular Arrhythmia/Ventricular Tachycardia (VT/VF)
Time frame: Through study completion, an average of 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 31078637Upadhyay GA, Vijayaraman P, Nayak HM, Verma N, Dandamudi G, Sharma PS, Saleem M, Mandrola J, Genovese D, Tung R; His-SYNC Investigators. His Corrective Pacing or Biventricular Pacing for Cardiac Resynchronization in Heart Failure. J Am Coll Cardiol. 2019 Jul 9;74(1):157-159. doi: 10.1016/j.jacc.2019.04.026. Epub 2019 May 9. No abstract available.
- Results publication: PubMed 31096064Upadhyay GA, Vijayaraman P, Nayak HM, Verma N, Dandamudi G, Sharma PS, Saleem M, Mandrola J, Genovese D, Oren JW, Subzposh FA, Aziz Z, Beaser A, Shatz D, Besser S, Lang RM, Trohman RG, Knight BP, Tung R; His-SYNC Investigators. On-treatment comparison between corrective His bundle pacing and biventricular pacing for cardiac resynchronization: A secondary analysis of the His-SYNC Pilot Trial. Heart Rhythm. 2019 Dec;16(12):1797-1807. doi: 10.1016/j.hrthm.2019.05.009. Epub 2019 May 13.
- Individual participant dataSharing planned: No
Related trials for Congestive Heart Failure
RecruitingPhase 2/3
Efficacy, Safety, and Pharmacokinetics of Vericiguat in Pediatric Participants With Heart Failure Due to Left Ventricular Systolic Dysfunction (MK-1242-036)
Heart Failure, Left Ventricular Systolic Dysfunction
RecruitingPhase 1/2
HS235 Study in Overweight and Obese Participants With Combined Pre and Post-Capillary Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction
Pulmonary Hypertension, Heart Failure With Preserved Ejection Fraction
Active, not recruiting
Heart Failure Patient Management and Interventions Using Continuous Patient Monitoring Outside Hospitals and Real-world Data
Chronic Heart Failure, Heart Transplant Recipient
Enrolling by invitationObservational study
Multi-Scale Analysis of Phenotypes in Heart Failure (MAP-HEART)
Heart Failure
Not yet recruitingObservational study
Real-world Effectiveness and Safety of Savagen (Sacubitril/Valsartan) in Malaysian HFrEF Patients
Heart Failure With Reduced Ejection Fraction (HFrEF), Heart Failure
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.
Roderick Tung, MD principal investigator
University of Chicago
Gaurav A. Upadhyay, MD principal investigator
University of Chicago
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CRT Pacemaker in people with Congestive Heart Failure, run by University of Chicago at 8 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 11 inclusion and 5 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 5 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Left Ventricular Ejection Fraction (LVEF) (time frame: baseline and 6 months). The study lists 3 primary outcomes in all. 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 NCT02700425, which also lists 2 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 5 Sep 2021.