Heart Failure With Reduced Ejection FractionHISalternativeNCT03614169
Direct HIS-pacing as an Alternative to BiV-pacing in Symptomatic HFrEF Patients With True LBBB
A study testing Implantation of a HIS-pacing lead and Implantation of a LV-pacing lead in people with Heart Failure With Reduced Ejection Fraction and Left Bundle-Branch Block, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
Trial summary
The present study will randomize 50 symptomatic heart failure patients with severely reduced left ventricular ejection fraction (LVEF) and a true left bundle branch block to either direct HIS-pacing or biventricular pacing and follow them for at least six months. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure With Reduced Ejection Fraction, Left Bundle-Branch Block
- What is being tested?
- Implantation of a HIS-pacing lead and Implantation of a LV-pacing lead
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteDenmark
- Study dates
- 9 Sep 2018to 10 Dec 2020
- Phase
- Interventional
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with ischaemic or non-ischaemic cardiomyopathy
- LVEF ≤ 35 % as assessed by echocardiography
- New York Heart Association (NYHA) class II-IV despite optimal medical therapy
- Either found eligible for cardiac resynchronization therapy (CRT-P or CRT-D) because of sinus rhythm and "true" LBBB according to Strauss criteria on a 12-lead ECG
- or found eligible for upgrade of an existing pacing system to cardiac resynchronization therapy (CRT-P or CRT-D) because of sinus rhythm and "true" LBBB according to Strauss criteria on a 12-lead ECG or at least 90 % right ventricular pacing in the preceding two months.
- Signed informed consent
Who cannot join
- Existing biventricular pacing system
- Permanent atrial fibrillation
- Severe kidney failure (eGFR < 30 ml/min)
- Acute myocardial infarction or Coronary By-pass Grafting within the preceding three months
- unwillingness to participate
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Direct HIS-pacing as an Alternative to Biventricular Pacing in Symptomatic Heart Failure Patients With Severely Reduced LVEF and a True Left Bundle Branch Block
The present study will randomize 50 symptomatic heart failure patients with severely reduced left ventricular ejection fraction (LVEF) and a true left bundle branch block to either direct HIS-pacing or biventricular pacing and follow them for at least six months. The outcome is how often it is possible to achieve HIS-pacing at implant and during follow-up and if HIS-pacing leads to differences in symptoms or measurable clinical parameters as compared to biventricular pacing.
Read the detailed description
Biventricular (BiV) pacing is an established treatment of symptomatic heart failure patients with severely reduced left ventricular ejection fraction (HFrEF) and wide QRS due to bundle branch block (BBB) on a 12-lead ECG. BiV pacing is normally achieved with an endocardial pacing lead in the right ventricle and an epicardial lead over the left ventricle situated in a coronary vein. BiV pacing does not correct the BBB but corrects the mechanical dyssynchrony that is a consequence of the BBB. It has been shown to work best on patients with "true" left bundle branch block (LBBB) where the block is due to disease within the conduction system (and not for example left ventricular hypertrophy or scars). Even if the patient is an ideal candidate for BiV pacing it can sometimes be difficult to achieve the best mechanical resynchronization because of anatomic difficulties, high pacing thresholds or phrenic nerve capture.
In recent years it has been demonstrated that the level of block in true LBBB is often within the bundle of HIS and it is possible in many cases to place a pacing lead distally to the site of block and get capture of both right and left bundles thereby "correcting" the BBB and achieve a normal or near-normal QRS complex. If the conduction system is intact distal to the block this mode of pacing leads to complete resynchronization of the ventricles. HIS-pacing can be achieved as either selective HIS-capture where it is only the conduction system that is paced leading to a narrow QRS complex. However, mostly it is achieved with non-selective HIS-capture where both the septal myocardium close to the pacing site and the His-bundle is captured. This leads to a QRS resembling the QRS achieved by selective HIS-capture but preceded by a delta-wave-like deflection which broadens the QRS complex. Since it is only a small part of the septum that is captured early this does not influence the resynchronization of the heart. In some patients HIS-pacing cannot be achieved due to anatomical difficulties that hinders reaching the HIS bundle with the present tools available. In others it is not possible to come distal to the block and recruiting both the left and the right bundle branch.
There is to date no randomized studies between HIS-bundle pacing and BiV pacing in HFrEF patients with LBBB but there are several case reports and retrospective data on successful HIS-bundle pacing in these patients. The present study will randomize 50 patients in a single centre to HIS-pacing or BiV pacing to determine to which extent it is possible to achieve normalization or near-normalization of the QRS with HIS-bundle pacing and what this translates to with regard to symptom relieve, walking distance, echocardiographic measures and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels as compared to BiV pacing.
- Being tested
- Implantation of a HIS-pacing lead, Implantation of a LV-pacing lead
- Keywords
- HIS-pacing, Biventricular pacing
- Medical subject headings
- Bundle-Branch Block
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Implantation of a HIS-pacing leadProcedure or surgery
This intervention is attempted first
Implantation of a LV-pacing leadProcedure or surgery
This intervention is attempted first
| Study group | Role | What they receive |
|---|---|---|
| Direct HIS-pacing | Experimental | In this arm a right ventricular (RV) lead or implantable cardioverter defibrillator (ICD) lead is placed first and then implantation of a HIS-pacing lead is attempted. If it is not possible to find and pace HIS or it is not possible to correct the LBBB, a left ventricular (LV) lead is implanted instead. Receives: Procedure: Implantation of a HIS-pacing lead |
| Biventricular pacing | Active comparator | In this arm an RV-lead or ICD-lead is placed first and then implantation of a LV-pacing lead is attempted. If this is not possible due to anatomical difficulties (no coronary sinus (CS) access, no available branches other than v cordis anterior or v cordis media) or electrical difficulties (no capture below 4 V at 1.0 msec or phrenic nerve stimulation < 2x pacing threshold) Receives: Procedure: Implantation of a LV-pacing lead |
What is being measured
The primary outcome is the main question the study is designed to answer.
Success rate of obtaining capture of HIS-bundle with narrowing of the QRS-duration
What is the success rate of implanting a pacing lead to the HIS bundle with narrowing of the QRS duration and maintaining this effect during the course of the study
Measured: 6 months
Secondary outcomes (1)
Fall in end-systolic volume > 15%
How many HIS-paced patients as opposed to BiV paced patients have a fall in end-systolic volume > 15 % of the initial value?
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 posted3 Aug 2018
- Study start9 Sep 2018
- Primary completion10 Nov 2020
- Study completion10 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart Failure With Reduced Ejection FractionStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe 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
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael Vinther, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03614169
- Sponsor's protocol ID
- HIS-alternative
- Acronym
- HISalternative
- Status last verified
- Jul 2021
- First submitted
- 29 Jul 2018
- Last updated
- 23 Jul 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Vinther M, Risum N, Svendsen JH, Mogelvang R, Philbert BT. A Randomized Trial of His Pacing Versus Biventricular Pacing in Symptomatic HF Patients With Left Bundle Branch Block (His-Alternative). JACC Clin Electrophysiol. 2021 Nov;7(11):1422-1432. doi: 10.1016/j.jacep.2021.04.003. Epub 2021 Apr 25.
PubMed 34167929
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Direct HIS-pacing as an Alternative to Biventricular Pacing in Symptomatic Heart Failure Patients With Severely Reduced LVEF and a True Left Bundle Branch Block
- ClinicalTrials.gov ID
- NCT03614169
- Acronym / sponsor ID
- HISalternative / HIS-alternative
- Keywords
- HIS-pacing, Biventricular pacing
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Study start
- 9 Sep 2018 (actual)
- Primary completion
- 10 Nov 2020 (actual)
- Study completion
- 10 Dec 2020 (actual)
- First posted
- 3 Aug 2018 (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 present study will randomize 50 symptomatic heart failure patients with severely reduced left ventricular ejection fraction (LVEF) and a true left bundle branch block to either direct HIS-pacing or biventricular pacing and follow them for at least six months. The outcome is how often it is possible to achieve HIS-pacing at implant and during follow-up and if HIS-pacing leads to differences in symptoms or measurable clinical parameters as compared to biventricular pacing.
Detailed description
Biventricular (BiV) pacing is an established treatment of symptomatic heart failure patients with severely reduced left ventricular ejection fraction (HFrEF) and wide QRS due to bundle branch block (BBB) on a 12-lead ECG. BiV pacing is normally achieved with an endocardial pacing lead in the right ventricle and an epicardial lead over the left ventricle situated in a coronary vein. BiV pacing does not correct the BBB but corrects the mechanical dyssynchrony that is a consequence of the BBB. It has been shown to work best on patients with "true" left bundle branch block (LBBB) where the block is due to disease within the conduction system (and not for example left ventricular hypertrophy or scars). Even if the patient is an ideal candidate for BiV pacing it can sometimes be difficult to achieve the best mechanical resynchronization because of anatomic difficulties, high pacing thresholds or phrenic nerve capture.
In recent years it has been demonstrated that the level of block in true LBBB is often within the bundle of HIS and it is possible in many cases to place a pacing lead distally to the site of block and get capture of both right and left bundles thereby "correcting" the BBB and achieve a normal or near-normal QRS complex. If the conduction system is intact distal to the block this mode of pacing leads to complete resynchronization of the ventricles. HIS-pacing can be achieved as either selective HIS-capture where it is only the conduction system that is paced leading to a narrow QRS complex. However, mostly it is achieved with non-selective HIS-capture where both the septal myocardium close to the pacing site and the His-bundle is captured. This leads to a QRS resembling the QRS achieved by selective HIS-capture but preceded by a delta-wave-like deflection which broadens the QRS complex. Since it is only a small part of the septum that is captured early this does not influence the resynchronization of the heart. In some patients HIS-pacing cannot be achieved due to anatomical difficulties that hinders reaching the HIS bundle with the present tools available. In others it is not possible to come distal to the block and recruiting both the left and the right bundle branch.
There is to date no randomized studies between HIS-bundle pacing and BiV pacing in HFrEF patients with LBBB but there are several case reports and retrospective data on successful HIS-bundle pacing in these patients. The present study will randomize 50 patients in a single centre to HIS-pacing or BiV pacing to determine to which extent it is possible to achieve normalization or near-normalization of the QRS with HIS-bundle pacing and what this translates to with regard to symptom relieve, walking distance, echocardiographic measures and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels as compared to BiV pacing.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Direct HIS-pacing | Experimental | Procedure: Implantation of a HIS-pacing leadIn this arm a right ventricular (RV) lead or implantable cardioverter defibrillator (ICD) lead is placed first and then implantation of a HIS-pacing lead is attempted. If it is not possible to find and pace HIS or it is not possible to correct the LBBB, a left ventricular (LV) lead is implanted instead. |
| Biventricular pacing | Active comparator | Procedure: Implantation of a LV-pacing leadIn this arm an RV-lead or ICD-lead is placed first and then implantation of a LV-pacing lead is attempted. If this is not possible due to anatomical difficulties (no coronary sinus (CS) access, no available branches other than v cordis anterior or v cordis media) or electrical difficulties (no capture below 4 V at 1.0 msec or phrenic nerve stimulation < 2x pacing threshold) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients with ischaemic or non-ischaemic cardiomyopathy
- LVEF ≤ 35 % as assessed by echocardiography
- New York Heart Association (NYHA) class II-IV despite optimal medical therapy
- Either found eligible for cardiac resynchronization therapy (CRT-P or CRT-D) because of sinus rhythm and "true" LBBB according to Strauss criteria on a 12-lead ECG
- or found eligible for upgrade of an existing pacing system to cardiac resynchronization therapy (CRT-P or CRT-D) because of sinus rhythm and "true" LBBB according to Strauss criteria on a 12-lead ECG or at least 90 % right ventricular pacing in the preceding two months.
Key exclusion criteria (5 listed)
- Existing biventricular pacing system
- Permanent atrial fibrillation
- Severe kidney failure (eGFR < 30 ml/min)
- Acute myocardial infarction or Coronary By-pass Grafting within the preceding three months
- unwillingness to participate
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 |
|---|---|---|
| Implantation of a HIS-pacing leadThis intervention is attempted first | Procedure or surgery | Direct HIS-pacing |
| Implantation of a LV-pacing leadThis intervention is attempted first | Procedure or surgery | Biventricular pacing |
Primary outcome
Success rate of obtaining capture of HIS-bundle with narrowing of the QRS-duration
Time frame: 6 months
What is the success rate of implanting a pacing lead to the HIS bundle with narrowing of the QRS duration and maintaining this effect during the course of the study
1 secondary outcome
Fall in end-systolic volume > 15%
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 23 Jul 2021.
- Results publication: PubMed 34167929Vinther M, Risum N, Svendsen JH, Mogelvang R, Philbert BT. A Randomized Trial of His Pacing Versus Biventricular Pacing in Symptomatic HF Patients With Left Bundle Branch Block (His-Alternative). JACC Clin Electrophysiol. 2021 Nov;7(11):1422-1432. doi: 10.1016/j.jacep.2021.04.003. Epub 2021 Apr 25.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Implantation of a HIS-pacing lead and Implantation of a LV-pacing lead in people with Heart Failure With Reduced Ejection Fraction and Left Bundle-Branch Block, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
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 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 23 Jul 2021. 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 Denmark. 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?
Success rate of obtaining capture of HIS-bundle with narrowing of the QRS-duration (time frame: 6 months). 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 NCT03614169, which also lists 1 linked publication.
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 23 Jul 2021.