Tricuspid Valve InsufficiencyNCT02314897
Left Ventricular Pacing to Prevent Iatrogenic TR Pilot Study
A study testing LV pacing and RV pacing in people with Tricuspid Valve Insufficiency and Sick Sinus Syndrome, run by National University Hospital, Singapore at 1 site in Singapore.
Trial summary
Background and Aims Pacemaker implantation for treating bradyarrhythmias typically involves placing a pacing lead through the tricuspid valve (TV) into the right ventricular (RV) apex. It is now known that tricuspid regurgitation (TR) frequently results from this and may lead to increased morbidity or mortality. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Tricuspid Valve Insufficiency, Sick Sinus Syndrome
- What is being tested?
- LV pacing and RV pacing
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteSingapore
- Study dates
- Jan 2015to Dec 2018
- 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 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients undergoing dual chamber permanent pacemaker implantation for sick sinus syndrome. This is defined as symptomatic sinus node dysfunction manifest as sinus pauses or excessive sinus bradycardia and is diagnosed on continuous ECG monitoring or ambulatory ECG recording (Holter study).
- Aged ≥21 years and able to give informed consent. The age limit is so that all patients are able to give informed consent personally.
Who cannot join
- 1. Left ventricular ejection fraction <40%. 2. Mobitz Type 2 second degree atrioventricular block, 2:1 atrioventricular block, high degree atrioventricular block or complete heart block.
- Life expectancy less than 1 year due to medical co-morbidities.
- Previous mechanical prosthetic tricuspid valve replacement, precluding the implantation of a right ventricular apical lead.
- Tricuspid regurgitation that is at least moderate in severity.
- Complex congenital heart disease precluding the placement of either a right ventricular apical lead or left ventricular lead via the coronary sinus
- Vascular or coronary sinus anatomy unfavourable to either conventional RV lead or left ventricular lead implantation as confirmed on a coronary sinus venography at the time of implantation.
- Pregnancy.
Trial locations and contacts
1 site in 1 country.
Singapore1 site, 1 recruiting
- Recruiting
National University Hospital
Singapore, 119074
Toon Wei Lim, MBBS, PhD, 65-67725286, toon_wei_lim@nuhs.edu.sg
Office of Biomedical Research, 65-65168425, obr@nuh.com.sg
About this study
Official title: Left Ventricular Pacing to Prevent Iatrogenic Tricuspid Regurgitation Caused by Conventional Right Ventricular Pacing: a Pilot Study
Background and Aims Pacemaker implantation for treating bradyarrhythmias typically involves placing a pacing lead through the tricuspid valve (TV) into the right ventricular (RV) apex. It is now known that tricuspid regurgitation (TR) frequently results from this and may lead to increased morbidity or mortality. Recently, left ventricular (LV) pacing through an epicardial vein via the coronary sinus has been widely practiced due to the advent of biventricular pacing. This lead does not cross the TV, potentially reducing the risk of TV dysfunction and may also reduce the risk of LV dysfunction. The investigators hypothesize that LV pacing will prevent the onset of new TR or worsening of pre-existing TR in patients undergoing pacemaker implantation.
Methods Patients receiving a pacemaker for sick sinus syndrome (n=20) with an LV ejection fraction <40% will be randomly allocated to receive either conventional RV pacing or LV pacing via the coronary sinus. Serial 2D and 3D transthoracic echocardiography will be performed before implantation, one day post implantation, then at 1 week, 1 month, 6 months and 1 year. The primary endpoints will be new onset TR and the diagnosis of at least moderate TR. Other endpoints include biventricular function, ventricular dyssynchrony, complications of device implantation, mortality and major cardiovascular events.
Read the detailed description
We hypothesize that left ventricular pacing via a coronary sinus approach can reduce the incidence of significant tricuspid regurgitation after pacemaker implantation in patients with normal left ventricular function.
The aim of this study is to compare the degree of tricuspid regurgitation caused by pacemaker implantation between the conventional techniques of implanting a ventricular lead implanted in the right ventricular apex versus implanting a ventricular lead in a left ventricular epicardial vein via a coronary sinus approach.
The secondary objective of our study is to evaluate whether left ventricular pacing is also less likely to cause ventricular dyssynchrony and dysfunction than right ventricular apical pacing.
This study is a single centre randomised clinical pilot study comparing 2 different lead implantation techniques to be assessed using both imaging techniques and follow up for clinical outcomes.
(i) Proposed study interventions The procedures in both arms of the study will be identical except for where the ventricular lead is placed. All parts of these procedures, including all the implanting equipment and pacing leads are standard routine clinical practice. The left ventricular leads used in this study are routinely used for pacing the left ventricle in patients receiving biventricular pacemakers or defibrillators for heart failure.
The implant site will be the left or right prepectoral region and venous access will be via either an axillary or subclavian vein approach. These choices will be left to the implanting physician's discretion. Once venous access has been established successfully the patient will then be randomly allocated to either of the study arms.
Patients randomized to have an LV lead will have a long coronary sinus sheath inserted which will be used to perform an occlusive venogram of the coronary sinus to determine if there are veins suitable for left ventricular lead placement. Those in the left ventricular pacing arm will instead have a left ventricular epicardial pacing lead placed as apically as possible in a large calibre left ventricular branch of the coronary sinus.
Patients in the right ventricular apical pacing arm will have an endocardial active fixation pacing leads placed in the right ventricular apex in the conventional manner.
Patients in both arms will then go on to have a right atrial active fixation lead placed in the right atrial appendage.
(ii) Methods for protecting against other sources of bias All patients referred to our Arrhythmia Service will be assessed for suitability to take part in this study. Once recruited, study subjects will be block randomised in a 1:1 fashion to either conventional right ventricular lead implantation or left ventricular coronary sinus lead implantation. They will be blinded to their allocation during the course of this study to remove any bias.
Assessment of the echocardiograms will be performed by 2 investigators who are not blinded to the patient's treatment allocation. This is because the pacemaker lead is nearly always well visualised during echocardiographic studies making blinding impossible. However, the main outcomes of this study will be quantitative measures of TR and biventricular function derived from 3D echocardiography rather than qualitative measures used in previous studies and this will protect against bias that may be caused by the echocardiogram assessors knowing the allocation of the patients. The studies will also be assessed for interobserver and intraobserver variability to look for the likelihood of bias.
(iii) Duration of follow up period Patients will be seen post discharge at 1 week for wound care and at 1 months, 6 months and 12 months for pacemaker checks in the pacemaker clinic.
(iv) Frequency and duration of follow-up The scheduled follow up is as follows. Note that all transthoracic echocardiography studies will include both 2D and 3D echocardiography
- Pre implant: transthoracic echocardiography
- Pacemaker implantation: randomisation when venous access is achieved. Blood samples taken for biomarker assays.
- Post implant day 1: Pacemaker check, transthoracic echocardiography
- Post implant week 1: Wound check, pacemaker check, transthoracic echocardiography
- Post implant month 1: Wound check, pacemaker check, transthoracic echocardiography
- Post implant month 6: Pacemaker check, transthoracic echocardiography, blood samples taken for biomarker assays.
- Post implant month 12: Pacemaker check, transthoracic echocardiography
- Conditions
- Tricuspid Valve Insufficiency, Sick Sinus Syndrome
- Being tested
- LV pacing, RV pacing
- Medical subject headings
- Tricuspid Valve Insufficiency, Sick Sinus Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LV pacingDevice
Left ventricular pacing lead implanted via the coronary sinus.
RV pacingDevice
Conventional right ventricular pacing.
| Study group | Role | What they receive |
|---|---|---|
| LV pacing | Experimental | Left ventricular pacing lead implanted via coronary sinus Receives: Device: LV pacing |
| RV pacing | Active comparator | Conventional right ventricular pacing lead. Receives: Device: RV pacing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Development of moderate or worse TR post implantation
At least moderate of worsening of tricuspid regurgitation at 6 months post implantation on echocardiography
Measured: 6 months
Secondary outcomes (6)
Biventricular ventricular function and dyssynchrony
Echocardiographically determined LV function, RV function, interventricular and intra ventricular dyssynchrony at 6 months.
Measured: 6 months
Major cardiovascular events
Cardiovascular mortality, hospitalizations, heart failure, stroke, MI
Measured: 6 months
All cause mortality
All cause mortality
Measured: 6 months
Biomarkers of heart failure
Change in plasma concentrations over 6 months of NT-proBNP, hsTnT and GDF15
Measured: 6 months
Lead performance parameters
Change in lead parameters over 6 months, including sensed R wave amplitude, impedance, capture threshold.
Measured: 6 months
Procedural complications and device related complications
Procedural complications and device related complications
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 posted11 Dec 2014 (estimated)
- Study startJan 2015
- Primary completionDec 2018 (estimated)
- Study completionDec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tricuspid Valve InsufficiencyStudies of the same condition, open and under way.
- 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
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Toon Wei Lim, MBBS, PhD, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02314897
- Sponsor's protocol ID
- 2014/00258
- Other IDs
- 2014
- Status last verified
- Apr 2017
- First submitted
- 8 Dec 2014
- Last updated
- 26 Feb 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Left Ventricular Pacing to Prevent Iatrogenic Tricuspid Regurgitation Caused by Conventional Right Ventricular Pacing: a Pilot Study
- ClinicalTrials.gov ID
- NCT02314897
- Acronym / sponsor ID
- 2014/00258
- Conditions
- Tricuspid Valve Insufficiency, Sick Sinus Syndrome
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Study start
- Jan 2015 (actual)
- Primary completion
- Dec 2018 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 11 Dec 2014 (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.
Background and Aims Pacemaker implantation for treating bradyarrhythmias typically involves placing a pacing lead through the tricuspid valve (TV) into the right ventricular (RV) apex. It is now known that tricuspid regurgitation (TR) frequently results from this and may lead to increased morbidity or mortality. Recently, left ventricular (LV) pacing through an epicardial vein via the coronary sinus has been widely practiced due to the advent of biventricular pacing. This lead does not cross the TV, potentially reducing the risk of TV dysfunction and may also reduce the risk of LV dysfunction. The investigators hypothesize that LV pacing will prevent the onset of new TR or worsening of pre-existing TR in patients undergoing pacemaker implantation.
Methods Patients receiving a pacemaker for sick sinus syndrome (n=20) with an LV ejection fraction <40% will be randomly allocated to receive either conventional RV pacing or LV pacing via the coronary sinus. Serial 2D and 3D transthoracic echocardiography will be performed before implantation, one day post implantation, then at 1 week, 1 month, 6 months and 1 year. The primary endpoints will be new onset TR and the diagnosis of at least moderate TR. Other endpoints include biventricular function, ventricular dyssynchrony, complications of device implantation, mortality and major cardiovascular events.
Detailed description
We hypothesize that left ventricular pacing via a coronary sinus approach can reduce the incidence of significant tricuspid regurgitation after pacemaker implantation in patients with normal left ventricular function.
The aim of this study is to compare the degree of tricuspid regurgitation caused by pacemaker implantation between the conventional techniques of implanting a ventricular lead implanted in the right ventricular apex versus implanting a ventricular lead in a left ventricular epicardial vein via a coronary sinus approach.
The secondary objective of our study is to evaluate whether left ventricular pacing is also less likely to cause ventricular dyssynchrony and dysfunction than right ventricular apical pacing.
This study is a single centre randomised clinical pilot study comparing 2 different lead implantation techniques to be assessed using both imaging techniques and follow up for clinical outcomes.
(i) Proposed study interventions The procedures in both arms of the study will be identical except for where the ventricular lead is placed. All parts of these procedures, including all the implanting equipment and pacing leads are standard routine clinical practice. The left ventricular leads used in this study are routinely used for pacing the left ventricle in patients receiving biventricular pacemakers or defibrillators for heart failure.
The implant site will be the left or right prepectoral region and venous access will be via either an axillary or subclavian vein approach. These choices will be left to the implanting physician's discretion. Once venous access has been established successfully the patient will then be randomly allocated to either of the study arms.
Patients randomized to have an LV lead will have a long coronary sinus sheath inserted which will be used to perform an occlusive venogram of the coronary sinus to determine if there are veins suitable for left ventricular lead placement. Those in the left ventricular pacing arm will instead have a left ventricular epicardial pacing lead placed as apically as possible in a large calibre left ventricular branch of the coronary sinus.
Patients in the right ventricular apical pacing arm will have an endocardial active fixation pacing leads placed in the right ventricular apex in the conventional manner.
Patients in both arms will then go on to have a right atrial active fixation lead placed in the right atrial appendage.
(ii) Methods for protecting against other sources of bias All patients referred to our Arrhythmia Service will be assessed for suitability to take part in this study. Once recruited, study subjects will be block randomised in a 1:1 fashion to either conventional right ventricular lead implantation or left ventricular coronary sinus lead implantation. They will be blinded to their allocation during the course of this study to remove any bias.
Assessment of the echocardiograms will be performed by 2 investigators who are not blinded to the patient's treatment allocation. This is because the pacemaker lead is nearly always well visualised during echocardiographic studies making blinding impossible. However, the main outcomes of this study will be quantitative measures of TR and biventricular function derived from 3D echocardiography rather than qualitative measures used in previous studies and this will protect against bias that may be caused by the echocardiogram assessors knowing the allocation of the patients. The studies will also be assessed for interobserver and intraobserver variability to look for the likelihood of bias.
(iii) Duration of follow up period Patients will be seen post discharge at 1 week for wound care and at 1 months, 6 months and 12 months for pacemaker checks in the pacemaker clinic.
(iv) Frequency and duration of follow-up The scheduled follow up is as follows. Note that all transthoracic echocardiography studies will include both 2D and 3D echocardiography
- Pre implant: transthoracic echocardiography
- Pacemaker implantation: randomisation when venous access is achieved. Blood samples taken for biomarker assays.
- Post implant day 1: Pacemaker check, transthoracic echocardiography
- Post implant week 1: Wound check, pacemaker check, transthoracic echocardiography
- Post implant month 1: Wound check, pacemaker check, transthoracic echocardiography
- Post implant month 6: Pacemaker check, transthoracic echocardiography, blood samples taken for biomarker assays.
- Post implant month 12: Pacemaker check, transthoracic echocardiography
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LV pacing | Experimental | Device: LV pacingLeft ventricular pacing lead implanted via coronary sinus |
| RV pacing | Active comparator | Device: RV pacingConventional right ventricular pacing lead. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients undergoing dual chamber permanent pacemaker implantation for sick sinus syndrome. This is defined as symptomatic sinus node dysfunction manifest as sinus pauses or excessive sinus bradycardia and is diagnosed on continuous ECG monitoring or ambulatory ECG recording (Holter study).
- Aged ≥21 years and able to give informed consent. The age limit is so that all patients are able to give informed consent personally.
Key exclusion criteria (7 listed)
- 1. Left ventricular ejection fraction <40%. 2. Mobitz Type 2 second degree atrioventricular block, 2:1 atrioventricular block, high degree atrioventricular block or complete heart block.
- Life expectancy less than 1 year due to medical co-morbidities.
- Previous mechanical prosthetic tricuspid valve replacement, precluding the implantation of a right ventricular apical lead.
- Tricuspid regurgitation that is at least moderate in severity.
- Complex congenital heart disease precluding the placement of either a right ventricular apical lead or left ventricular lead via the coronary sinus
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 |
|---|---|---|
| LV pacingLeft ventricular pacing lead implanted via the coronary sinus. | Device | LV pacing |
| RV pacingConventional right ventricular pacing. | Device | RV pacing |
Primary outcome
Development of moderate or worse TR post implantation
Time frame: 6 months
At least moderate of worsening of tricuspid regurgitation at 6 months post implantation on echocardiography
6 secondary outcomes
Biventricular ventricular function and dyssynchrony
Time frame: 6 months
Major cardiovascular events
Time frame: 6 months
All cause mortality
Time frame: 6 months
Biomarkers of heart failure
Time frame: 6 months
Lead performance parameters
Time frame: 6 months
Procedural complications and device related complications
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2018.
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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.
Toon Wei Lim, MBBS, PhD principal investigator
National University Hospital, Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing LV pacing and RV pacing in people with Tricuspid Valve Insufficiency and Sick Sinus Syndrome, run by National University Hospital, Singapore at 1 site in Singapore.
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 2 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 26 Feb 2018. 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 Singapore. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Timothy Chia (65-6772 7563, medccpt@nus.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Development of moderate or worse TR post implantation (time frame: 6 months). 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 26 Feb 2018.