Coronary Artery DiseasePhase 4MICRO-PCINCT02507050
Ivabradine and Post-revascularisation Microcirculatory Dysfunction
A Phase 4 study testing Ivabradine in people with Coronary Artery Disease and Angina, run by Liverpool Heart and Chest Hospital NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
The aim of the study is to test whether, in patients with angina and flow limiting epicardial coronary artery disease, pre-treatment with Ivabradine, as opposed to beta blockers, will reduce post percutaneous coronary intervention induced microvascular dysfunction. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease, Angina
- What is being tested?
- Ivabradine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Mar 2016to Mar 2016
- Phase
- Phase 4
- 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
- Symptoms of Angina Pectoris
- Angiographic evidence of epicardial coronary artery stenosis referred for PCI
- Flow limiting lesion (Fractional Flow Reserve ≤0.80) in one of following locations (as defined in SYNTAX trial89):
- Proximal or mid left anterior descending artery (LAD)
- Proximal or mid dominant right coronary artery (RCA)
- Proximal left circumflex artery (LCx) or 1ST Obtuse marginal Vessel
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- Existing beta blocker prescription
- Echocardiogram performed within preceding 12 months
- Patient consent
Who cannot join
- Previous myocardial infarction (MI) in target vessel myocardial territory or any MI in preceding 12 months (defined by patient history, ECG changes and evidence of regional wall motion abnormalities on echocardiography)
- FFR>0.80 in target vessel at time of procedure
- Requirement for Multi-vessel intervention in a single procedure
- Any chronic total occlusion (100% epicardial occlusion) on angiography
- Distal coronary artery stenosis or that affecting non-dominant RCA
- Heart Rate <60 bpm at inclusion (assessed by 12 lead ECG after minimum 10 minutes rest period)
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- Any rhythm other than sinus rhythm
- Sick sinus syndrome or high grade atrio-ventricular block
- Permanent Pacemaker in situ
- Congenital QT Syndrome
- Intolerance or allergy to beta-blockers
- Intolerance to Ivabradine
- Additional (other than angina pectoris) indication for beta-blocker treatment e.g. ventricular tachycardia
- Concurrent required use of rate-limiting drugs other than beta-blockers
- The necessity of combination therapy with Ivabradine and bisoprolol to achieve heart rate control
- Contraindication to Magnetic Resonance Imaging or IV adenosine
- Severe impairment of renal function (eGFR<30ml/min)
- Severe Liver Disease (Any worse than Grade A by Child-Pugh Classification)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Can Ivabradine Attenuate Post-revascularisation Microcirculatory Dysfunction in Flow Limiting Coronary Artery Disease?
The aim of the study is to test whether, in patients with angina and flow limiting epicardial coronary artery disease, pre-treatment with Ivabradine, as opposed to beta blockers, will reduce post percutaneous coronary intervention induced microvascular dysfunction.
Read the detailed description
We will be recruiting patients with stable angina referred for percutaneous intervention (PCI) due to flow limiting coronary artery disease. All patients will be on an existing beta blocker prescription (standard first line angina therapy). Our hypothesis is that Ivabradine will attenuate microvascular dysfunction post PCI when compared to standard beta-blocker pre-treatment. We intend to test this in a randomised, open-label parallel arm study with a direct comparison between Ivabradine and beta-blockers (standard therapy). Patients will be randomised to receive either Ivabradine (and stop beta blockers) or continue beta blockers for 6 weeks prior to the PCI procedure. The primary endpoint will be IMR (index of microvascular resistance) post PCI, as a marker of microvascular dysfunction and procedural related myocardial injury. IMR is a potent marker of adverse outcome in STEMI patients and in ACS after PCI. Although this has yet to be assessed in the elective setting, a reduction in IMR with Ivabradine may indicate a potential to improve outcomes and lessen iatrogenic microvascular dysfunction post PCI. IMR is assessed using thermodilution catheters placed distal to the coronary stenosis and by producing hyperaemia. To assess the medium term effects on the microcirculation post PCI all patients will have a stress perfusion cardiac MRI 12 weeks post procedure. The secondary endpoint will be proportion of patients with coronary flow reserve (CFR) <2.0 in PCI territory (regional myocardial blood flow at hyperaemia by intravenous adenosine infusion compared to rest). We will also be assessing CFI (collateral flow index), as promotion of the collateral system is one method by which Ivabradine may lessen procedural related myocardial injury, and ΔIMR as the difference between IMR pre and post-PCI.
The measurement of cardiac troponins and use of cardiac MRI will facilitate the identification of peri-procedural myocardial injury and procedural related myocardial infarction as further secondary end points. The Seattle Angina Questionnaire will be used at 3 intervals to assess symptoms throughout the study. The total study length for each patient will be 18 weeks.
- Conditions
- Coronary Artery Disease, Angina
- Being tested
- Ivabradine
- Keywords
- Ivabradine, Microvascular dysfunction, PCI, Procedural related myocardial injury, IMR, Index of Microvascular Resistance
- Medical subject headings
- Coronary Artery Disease, Angina Pectoris
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IvabradineDrug
Also called Procoralan
To start Ivabradine 6 weeks prior to PCI.
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | Patients randomised to stop beta blockers and start Ivabradine. Initial dose of 5mg BD, titrated to 7.5mg BD if possible. Receives: Drug: Ivabradine |
| Standard therapy | No intervention | Bisoprolol given as standard beta blocker treatment i.e. Bisoprolol (maximum dose 10mg OD). |
What is being measured
The primary outcome is the main question the study is designed to answer.
IMR (Index of Microvascular Resistance)
Invasive marker of microvascular dysfunction
Measured: Immediately after PCI
Secondary outcomes (4)
Peri-procedural Troponin Release
Rise in high sensitivity troponin 3 hours after PCI
Measured: 3 hours after PCI
CFI pre-revascularisation
Collateral flow index is an invasively measured marker of collateral blood flow- to be measured prior to PCI
Measured: Immediately prior to PCI
Symptomatic Improvement (Seattle Angina Questionnaire)
Seattle Angina Questionnaire assessed at 18 weeks after starting treatment (12 weeks after PCI) and compared to baseline scores.
Measured: 18 weeks
Coronary Flow Reserve
Coronary Flow Reserve measured in target vessel on MRI at 12 weeks after PCI
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2015 (estimated)
- Study startMar 2016
- Primary completionMar 2016
- Study completionMar 2016
Why it stopped: Funding not yet achieved
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coronary Artery DiseaseStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Liverpool Heart and Chest Hospital NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Aleem Khand, MBChB MD, Principal investigator, Liverpool Heart and Chest Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02507050
- Sponsor's protocol ID
- 1060
- Acronym
- MICRO-PCI
- Status last verified
- Aug 2018
- First submitted
- 22 Jul 2015
- Last updated
- 17 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Can Ivabradine Attenuate Post-revascularisation Microcirculatory Dysfunction in Flow Limiting Coronary Artery Disease?
- ClinicalTrials.gov ID
- NCT02507050
- Acronym / sponsor ID
- MICRO-PCI / 1060
- Conditions
- Coronary Artery Disease, Angina
- Keywords
- Ivabradine, Microvascular dysfunction, PCI, Procedural related myocardial injury, IMR, Index of Microvascular Resistance
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Funding not yet achieved
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Liverpool Heart and Chest Hospital NHS Foundation TrustUniversity, hospital or other
- Study start
- Mar 2016 (actual)
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 23 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the study is to test whether, in patients with angina and flow limiting epicardial coronary artery disease, pre-treatment with Ivabradine, as opposed to beta blockers, will reduce post percutaneous coronary intervention induced microvascular dysfunction.
Detailed description
We will be recruiting patients with stable angina referred for percutaneous intervention (PCI) due to flow limiting coronary artery disease. All patients will be on an existing beta blocker prescription (standard first line angina therapy). Our hypothesis is that Ivabradine will attenuate microvascular dysfunction post PCI when compared to standard beta-blocker pre-treatment. We intend to test this in a randomised, open-label parallel arm study with a direct comparison between Ivabradine and beta-blockers (standard therapy). Patients will be randomised to receive either Ivabradine (and stop beta blockers) or continue beta blockers for 6 weeks prior to the PCI procedure. The primary endpoint will be IMR (index of microvascular resistance) post PCI, as a marker of microvascular dysfunction and procedural related myocardial injury. IMR is a potent marker of adverse outcome in STEMI patients and in ACS after PCI. Although this has yet to be assessed in the elective setting, a reduction in IMR with Ivabradine may indicate a potential to improve outcomes and lessen iatrogenic microvascular dysfunction post PCI. IMR is assessed using thermodilution catheters placed distal to the coronary stenosis and by producing hyperaemia. To assess the medium term effects on the microcirculation post PCI all patients will have a stress perfusion cardiac MRI 12 weeks post procedure. The secondary endpoint will be proportion of patients with coronary flow reserve (CFR) <2.0 in PCI territory (regional myocardial blood flow at hyperaemia by intravenous adenosine infusion compared to rest). We will also be assessing CFI (collateral flow index), as promotion of the collateral system is one method by which Ivabradine may lessen procedural related myocardial injury, and ΔIMR as the difference between IMR pre and post-PCI.
The measurement of cardiac troponins and use of cardiac MRI will facilitate the identification of peri-procedural myocardial injury and procedural related myocardial infarction as further secondary end points. The Seattle Angina Questionnaire will be used at 3 intervals to assess symptoms throughout the study. The total study length for each patient will be 18 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Drug: IvabradinePatients randomised to stop beta blockers and start Ivabradine. Initial dose of 5mg BD, titrated to 7.5mg BD if possible. |
| Standard therapy | No intervention | –Bisoprolol given as standard beta blocker treatment i.e. Bisoprolol (maximum dose 10mg OD). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Symptoms of Angina Pectoris
- Angiographic evidence of epicardial coronary artery stenosis referred for PCI
- Flow limiting lesion (Fractional Flow Reserve ≤0.80) in one of following locations (as defined in SYNTAX trial89):
- Existing beta blocker prescription
- Echocardiogram performed within preceding 12 months
Key exclusion criteria (18 listed)
- Previous myocardial infarction (MI) in target vessel myocardial territory or any MI in preceding 12 months (defined by patient history, ECG changes and evidence of regional wall motion abnormalities on echocardiography)
- FFR>0.80 in target vessel at time of procedure
- Requirement for Multi-vessel intervention in a single procedure
- Any chronic total occlusion (100% epicardial occlusion) on angiography
- Distal coronary artery stenosis or that affecting non-dominant RCA
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 |
|---|---|---|
| IvabradineAlso: ProcoralanTo start Ivabradine 6 weeks prior to PCI. | Drug | Intervention |
Primary outcome
IMR (Index of Microvascular Resistance)
Time frame: Immediately after PCI
Invasive marker of microvascular dysfunction
4 secondary outcomes
Peri-procedural Troponin Release
Time frame: 3 hours after PCI
CFI pre-revascularisation
Time frame: Immediately prior to PCI
Symptomatic Improvement (Seattle Angina Questionnaire)
Time frame: 18 weeks
Coronary Flow Reserve
Time frame: 12 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 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.
Aleem Khand, MBChB MD principal investigator
Liverpool Heart and Chest Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ivabradine in people with Coronary Artery Disease and Angina, run by Liverpool Heart and Chest Hospital 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 9 inclusion and 18 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: withdrawn, as of the sponsor's last update on 17 Aug 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 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
IMR (Index of Microvascular Resistance) (time frame: Immediately after PCI). 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 17 Aug 2018.