Heart FailurePhase 3NCT01417624
Cardiac Magnetic Resonance Imaging Guided Left Ventricular Lead Placement
A Phase 3 study testing CMR Guidance in terms of guiding LV lead implantation in people with Heart Failure, run by Royal Brompton & Harefield NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Heart failure is a common, costly, disabling and potentially lethal condition. Despite well recognised and proven drug therapies, many patients remain breathless on exertion. A special pacemaker (cardiac resynchronisation therapy) may help improve symptoms of breathlessness and survival by restoring coordinated… Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Heart Failure
- What is being tested?
- CMR Guidance in terms of guiding LV lead implantation
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Aug 2011to Jun 2013
- Phase
- Phase 3
- 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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able to give written informed consent
- Age >18 years old
- Successful CRT implantation (with or without a defibrillator)
- NYHA Class III-IV Heart Failure (or NYHA II with NYHA III/IV symptoms in the preceding 12 months)
- LVEF <35% (Calculated using echocardiography or Cardiac MR) at the time of implantation
- QRS duration > 120ms with Left Bundle Branch Block morphology on ECG
- Sinus Rhythm
- Optimal Tolerated Medical Therapy for Heart Failure
Who cannot join
- Severe, life threatening non cardiac disease
- Active malignant disease and recent (<5 years) malignant disease
- Prior Heart Transplant
- Recent history of unstable angina, acute coronary syndrome or myocardial infarction within three months of enrollment into the study
- Pregnancy
- Failure to participate in consent process
Show all 11Show fewer
- Atrial Fibrillation
- Conventional pacemaker in situ
- Heart Failure requiring constant intravenous therapy including diuretics and/or inotropes
- Recent revascularisation procedure i.e. coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) within the last three months
- Contraindications to a CMR study
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Royal Brompton Hospital
London, London, SW3 6NP
Rakesh Sharma, MRCP PhD
Kaushik Guha, MBBS MRCP
About this study
Official title: The Assessment of Cardiac Magnetic Resonance Imaging Guided Left Ventricular Lead Placement During the Implantation of Cardiac Resynchronisation Therapy on Clinical Outcomes in Patients With Chronic Heart Failure
Heart failure is a common, costly, disabling and potentially lethal condition. Despite well recognised and proven drug therapies, many patients remain breathless on exertion. A special pacemaker (cardiac resynchronisation therapy) may help improve symptoms of breathlessness and survival by restoring coordinated beating of the heart. However, despite careful planning and the knowledge of the most appropriate selection criteria, up to a third of patients do not get the desired beneficial effects after the pacemaker has been implanted.
The implantation of the special pacemaker requires three leads (wires) to be inserted within the heart. Currently this is undertaken under X-ray guidance. Some patients may have scarring of the heart muscle due to previous heart attacks or their underlying condition. The X-ray technique cannot see this and therefore the doctor may implant the lead in such an area of scar tissue. Cardiac magnetic resonance imaging (CMR) can demonstrate these areas of scar. The study aims to investigate whether CMR can better predict where the wires should be placed. The CMR pictures will be taken before the patient has the special pacemaker implanted.
Read the detailed description
Cardiac Resynchronisation Therapy (CRT) is currently recommended for patients with heart failure who have symptomatic left ventricular (LV) systolic impairment and a prolonged QRS duration.1, 2 Up to a third of patients post CRT implantation do not derive the anticipated clinical benefit. The reasons for this are multifactorial, with patient selection and successful LV lead implantation likely to be key factors.
The mechanism by which CRT exerts its clinical benefits is fundamentally through the correction of mechanical dyssynchrony. However, despite much research in this area the optimal measures of dyssynchrony for the selection of suitable candidates for CRT have not been established. The current guidelines were revised in light of the PROSPECT trial which failed to prove validity and reproducibility in complex echocardiographic variables of dyssynchrony.3 The 12 lead electrocardiogram (ECG) remains the most widely used criterion for the assessment of dyssynchrony in patients being considered for CRT, with patients with a broad QRS complex (>150ms) appearing to benefit the most.4, 5
Although the definition of left bundle branch block (LBBB) is well established, the precise electrophysiological characteristics remain poorly understood. An arbitrary 'cut off' of 120 milliseconds was recommended by the New York Heart Association (NYHA) in 1948 for its definition.6 This has subsequently become enshrined in the literature. The presence of LBBB, a heterogeneous entity, is associated with both electrical and mechanical abnormalities within the left ventricle.7 Septal and lateral wall delay frequently occur in this setting, with delayed activation of the lateral LV wall forming the basis for bi-ventricular pacing. It is well documented within populations with left ventricular impairment that there is prolongation of the QRS complex which is associated with an adverse prognosis.8
The success of CRT is reliant upon achieving an acceptable position of the left ventricular lead during implantation. The LV lead position needs to be anatomically stable to minimise the risk of lead displacement and also to avoid diaphragmatic capture. Furthermore, patients with myocardial scar tissue in the lateral LV segments as detected on CMR are known to have a worse outcome following CRT 9 and pacing such sites may potentially be pro-arrhythmic.10 It is not known whether CMR guided placement of the LV lead in order to avoid sites of myocardial scar and fibrosis can result in an improved clinical outcome in these patients.
A recently published study corroborates that myocardial scar in the region of activation of the LV lead may have a detrimental effect on the delivery of CRT. A consecutive series of 397 patients with ischaemic cardiomyopathy were imaged prior to the implantation of CRT. Using the complex echocardiographic technique of 'speckle tracking', myocardial scar was demonstrated to have an adverse effect on patients' outcomes. It remained an independent predictor of adverse clinical outcome. Notably due to the complexity of the technique, the presence of myocardial scar was validated using CMR.11
CRT response is a contentious subject. It is well recognised within the literature that approximately 30-40% of patients do not appear to improve clinically following CRT implantation.12 However, the inter-study variability of what has been considered as a marker of response has been wide and several different variables have been utilised.13 Several of the studies have also been small, single centre, and non-randomised. There is currently a lack of consensus in what constitutes 'response' vs 'non-response' following CRT, which may be either defined in terms of markers of LV reverse remodelling or changes in the clinical indices of heart failure or a combination of them both. In an effort to rationalise the endpoints of CRT trials, clinical composite scores have been devised inclusive of both imaging based and clinical endpoints. However, the correlation between both LV remodelling and clinical endpoints when compared using correlation coefficients is marginally better than chance. The realisation that clinical improvement post CRT implantation does not necessarily accompany mechanical remodelling has also confused the issue.
Rationale for Study The aim of the present study is to provide pilot data, the results of which should increase our understanding of the mechanisms by which CRT improves clinical outcomes in patients with heart failure.
- Conditions
- Heart Failure
- Being tested
- CMR Guidance in terms of guiding LV lead implantation
- Keywords
- Heart Failure, Cardiac Resynchronisation Therapy
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CMR Guidance in terms of guiding LV lead implantationOther
Also called A cardiac Magnetic resonance Scan using Gadolinium Contrast
Following randomisation, the optimal position of the LV lead will be determined either according to current standard criteria (as proposed by the primary operator) or with CMR guidance.
The CRT device will be implanted using established conventional techniques. The CMR study will be performed pre-implantation only. The distribution of myocardial scar and fibrosis will be derived from this study. A CMR venogram will also be generated and the suggested optimal venous tributaries of the great cardiac vein will be identified from discussion between the principal investigator and senior CMR physician. This information will be used for those in the active arm only.
| Study group | Role | What they receive |
|---|---|---|
| Control Group - Standard | Placebo comparator | This will be a randomised controlled unblinded prospective study recruiting patients in sinus rhythm with LBBB (QRS width ≥ 120ms) and a LV ejection fraction of below 35% who meet the current guidelines for CRT implantation. Patients will be randomised to one of two groups (1:1 randomisation)
Conventional LV lead placement - the LV lead will be placed according to standard techniques without knowledge of the patient's CMR findings Receives: Other: CMR Guidance in terms of guiding LV lead implantation |
| Active CMR guided Arm | Active comparator | This will be a randomised controlled unblinded prospective study recruiting patients in sinus rhythm with LBBB (QRS width ≥ 120ms) and a LV ejection fraction of below 35% who meet the current guidelines for CRT implantation.Patients will be randomised to one of two groups (1:1 randomisation):
CMR guided LV lead placement - an expert panel will decide pre-operatively the optimal branch of the coronary sinus for LV lead placement based on the presence of myocardial scar tissue and coronary sinus anatomy. The operator will informed as to the optimal vein to target for delivery of the LV lead. Should this be technically unfeasible (e.g. due to pacing considerations or stability of LV lead position), then the most suitable vein will be used at the time of implantation. Receives: Other: CMR Guidance in terms of guiding LV lead implantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
6 Minute Walk Test Distance
CMR guided LV lead placement during CRT implantation results in improved exercise tolerance at 12 months in patients with heart failure.
Measured: 12 months
Secondary outcomes (7)
Exercise Tolerance (MVO2)
Cardiopulmonary Exercise Testing (Peak Oxygen Consumption, MVO2)
Measured: 6, 12 months following CRT Implantation
Blood Tests - Serum BNP
- B Type Natriuretic Peptide (BNP)
Measured: 1, 6, 12 months following CRT Implantation
Clinical -NYHA Classification
NYHA Classification
Measured: 1, 6, 12 months following CRT
Quality of Life Questionnaires
Euroqol and Minnesota Quality of Life Questionnaires for HF
Measured: 1,6,12 months following CRT Implantation
Echocardiography
LVEF, LVEDD, LVESD, LVESV, LVEDV
Measured: 1,6,12 months following CRT Implantation
Pacing
Level of Bi Ventricular Pacing and atrial and ventricular arrythmia burden
Measured: 1,6,12 months following CRT Implantation
Blood Test -Urate
Serum Urate
Measured: 1,6,12 months following CRT Implantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2011 (estimated)
- Study startAug 2011
- Primary completionDec 2012 (estimated)
- Study completionJun 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies 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 3
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Royal Brompton & Harefield NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Investigators
- Rakesh Sharma, MRCP PhD, Principal investigator, Royal Brompton & Harefield NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01417624
- Sponsor's protocol ID
- RBH2011HS008B
- Status last verified
- Aug 2011
- First submitted
- 11 Aug 2011
- Last updated
- 16 Aug 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Assessment of Cardiac Magnetic Resonance Imaging Guided Left Ventricular Lead Placement During the Implantation of Cardiac Resynchronisation Therapy on Clinical Outcomes in Patients With Chronic Heart Failure
- ClinicalTrials.gov ID
- NCT01417624
- Acronym / sponsor ID
- RBH2011HS008B
- Conditions
- Heart Failure
- Keywords
- Heart Failure, Cardiac Resynchronisation Therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Royal Brompton & Harefield NHS Foundation TrustUniversity, hospital or other
- Study start
- Aug 2011
- Primary completion
- Dec 2012 (estimated)
- Study completion
- Jun 2013 (estimated)
- First posted
- 16 Aug 2011 (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.
Heart failure is a common, costly, disabling and potentially lethal condition. Despite well recognised and proven drug therapies, many patients remain breathless on exertion. A special pacemaker (cardiac resynchronisation therapy) may help improve symptoms of breathlessness and survival by restoring coordinated beating of the heart. However, despite careful planning and the knowledge of the most appropriate selection criteria, up to a third of patients do not get the desired beneficial effects after the pacemaker has been implanted.
The implantation of the special pacemaker requires three leads (wires) to be inserted within the heart. Currently this is undertaken under X-ray guidance. Some patients may have scarring of the heart muscle due to previous heart attacks or their underlying condition. The X-ray technique cannot see this and therefore the doctor may implant the lead in such an area of scar tissue. Cardiac magnetic resonance imaging (CMR) can demonstrate these areas of scar. The study aims to investigate whether CMR can better predict where the wires should be placed. The CMR pictures will be taken before the patient has the special pacemaker implanted.
Detailed description
Cardiac Resynchronisation Therapy (CRT) is currently recommended for patients with heart failure who have symptomatic left ventricular (LV) systolic impairment and a prolonged QRS duration.1, 2 Up to a third of patients post CRT implantation do not derive the anticipated clinical benefit. The reasons for this are multifactorial, with patient selection and successful LV lead implantation likely to be key factors.
The mechanism by which CRT exerts its clinical benefits is fundamentally through the correction of mechanical dyssynchrony. However, despite much research in this area the optimal measures of dyssynchrony for the selection of suitable candidates for CRT have not been established. The current guidelines were revised in light of the PROSPECT trial which failed to prove validity and reproducibility in complex echocardiographic variables of dyssynchrony.3 The 12 lead electrocardiogram (ECG) remains the most widely used criterion for the assessment of dyssynchrony in patients being considered for CRT, with patients with a broad QRS complex (>150ms) appearing to benefit the most.4, 5
Although the definition of left bundle branch block (LBBB) is well established, the precise electrophysiological characteristics remain poorly understood. An arbitrary 'cut off' of 120 milliseconds was recommended by the New York Heart Association (NYHA) in 1948 for its definition.6 This has subsequently become enshrined in the literature. The presence of LBBB, a heterogeneous entity, is associated with both electrical and mechanical abnormalities within the left ventricle.7 Septal and lateral wall delay frequently occur in this setting, with delayed activation of the lateral LV wall forming the basis for bi-ventricular pacing. It is well documented within populations with left ventricular impairment that there is prolongation of the QRS complex which is associated with an adverse prognosis.8
The success of CRT is reliant upon achieving an acceptable position of the left ventricular lead during implantation. The LV lead position needs to be anatomically stable to minimise the risk of lead displacement and also to avoid diaphragmatic capture. Furthermore, patients with myocardial scar tissue in the lateral LV segments as detected on CMR are known to have a worse outcome following CRT 9 and pacing such sites may potentially be pro-arrhythmic.10 It is not known whether CMR guided placement of the LV lead in order to avoid sites of myocardial scar and fibrosis can result in an improved clinical outcome in these patients.
A recently published study corroborates that myocardial scar in the region of activation of the LV lead may have a detrimental effect on the delivery of CRT. A consecutive series of 397 patients with ischaemic cardiomyopathy were imaged prior to the implantation of CRT. Using the complex echocardiographic technique of 'speckle tracking', myocardial scar was demonstrated to have an adverse effect on patients' outcomes. It remained an independent predictor of adverse clinical outcome. Notably due to the complexity of the technique, the presence of myocardial scar was validated using CMR.11
CRT response is a contentious subject. It is well recognised within the literature that approximately 30-40% of patients do not appear to improve clinically following CRT implantation.12 However, the inter-study variability of what has been considered as a marker of response has been wide and several different variables have been utilised.13 Several of the studies have also been small, single centre, and non-randomised. There is currently a lack of consensus in what constitutes 'response' vs 'non-response' following CRT, which may be either defined in terms of markers of LV reverse remodelling or changes in the clinical indices of heart failure or a combination of them both. In an effort to rationalise the endpoints of CRT trials, clinical composite scores have been devised inclusive of both imaging based and clinical endpoints. However, the correlation between both LV remodelling and clinical endpoints when compared using correlation coefficients is marginally better than chance. The realisation that clinical improvement post CRT implantation does not necessarily accompany mechanical remodelling has also confused the issue.
Rationale for Study The aim of the present study is to provide pilot data, the results of which should increase our understanding of the mechanisms by which CRT improves clinical outcomes in patients with heart failure.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control Group - Standard | Placebo comparator | Other: CMR Guidance in terms of guiding LV lead implantationThis will be a randomised controlled unblinded prospective study recruiting patients in sinus rhythm with LBBB (QRS width ≥ 120ms) and a LV ejection fraction of below 35% who meet the current guidelines for CRT implantation. Patients will be randomised to one of two groups (1:1 randomisation) Conventional LV lead placement - the LV lead will be placed according to standard techniques without knowledge of the patient's CMR findings |
| Active CMR guided Arm | Active comparator | Other: CMR Guidance in terms of guiding LV lead implantationThis will be a randomised controlled unblinded prospective study recruiting patients in sinus rhythm with LBBB (QRS width ≥ 120ms) and a LV ejection fraction of below 35% who meet the current guidelines for CRT implantation.Patients will be randomised to one of two groups (1:1 randomisation): CMR guided LV lead placement - an expert panel will decide pre-operatively the optimal branch of the coronary sinus for LV lead placement based on the presence of myocardial scar tissue and coronary sinus anatomy. The operator will informed as to the optimal vein to target for delivery of the LV lead. Should this be technically unfeasible (e.g. due to pacing considerations or stability of LV lead position), then the most suitable vein will be used at the time of implantation. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Able to give written informed consent
- Age >18 years old
- Successful CRT implantation (with or without a defibrillator)
- NYHA Class III-IV Heart Failure (or NYHA II with NYHA III/IV symptoms in the preceding 12 months)
- LVEF <35% (Calculated using echocardiography or Cardiac MR) at the time of implantation
Key exclusion criteria (11 listed)
- Severe, life threatening non cardiac disease
- Active malignant disease and recent (<5 years) malignant disease
- Prior Heart Transplant
- Recent history of unstable angina, acute coronary syndrome or myocardial infarction within three months of enrollment into the study
- Pregnancy
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 |
|---|---|---|
| CMR Guidance in terms of guiding LV lead implantationAlso: A cardiac Magnetic resonance Scan using Gadolinium ContrastFollowing randomisation, the optimal position of the LV lead will be determined either according to current standard criteria (as proposed by the primary operator) or with CMR guidance. The CRT device will be implanted using established conventional techniques. The CMR study will be performed pre-implantation only. The distribution of myocardial scar and fibrosis will be derived from this study. A CMR venogram will also be generated and the suggested optimal venous tributaries of the great cardiac vein will be identified from discussion between the principal investigator and senior CMR physician. This information will be used for those in the active arm only. | Other | Active CMR guided Arm, Control Group - Standard |
Primary outcome
6 Minute Walk Test Distance
Time frame: 12 months
CMR guided LV lead placement during CRT implantation results in improved exercise tolerance at 12 months in patients with heart failure.
7 secondary outcomes
Exercise Tolerance (MVO2)
Time frame: 6, 12 months following CRT Implantation
Blood Tests - Serum BNP
Time frame: 1, 6, 12 months following CRT Implantation
Clinical -NYHA Classification
Time frame: 1, 6, 12 months following CRT
Quality of Life Questionnaires
Time frame: 1,6,12 months following CRT Implantation
Echocardiography
Time frame: 1,6,12 months following CRT Implantation
Pacing
Time frame: 1,6,12 months following CRT Implantation
Blood Test -Urate
Time frame: 1,6,12 months following CRT Implantation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2011.
- Homepage for Royal Brompton \& Harefield NHS Foundation TrustLink provided by the sponsor.
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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.
Rakesh Sharma, MRCP PhD principal investigator
Royal Brompton & Harefield NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing CMR Guidance in terms of guiding LV lead implantation in people with Heart Failure, run by Royal Brompton & Harefield NHS Foundation Trust at 1 site in United Kingdom.
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 8 inclusion and 11 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 16 Aug 2011. 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 Kingdom. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Rakesh Sharma, MRCP PhD (00 44 207 352 8121 ext. 2060, rakesh.sharma@rbht.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
6 Minute Walk Test Distance (time frame: 12 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 16 Aug 2011.