Ignite Creation Date:
2025-12-25 @ 3:48 AM
Ignite Modification Date:
2026-02-23 @ 8:08 PM
Study NCT ID:
NCT06854302
Status:
ENROLLING_BY_INVITATION
Last Update Posted:
2025-03-03
First Post:
2024-12-24
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Angina After PCI: a Systems Medicine Study
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D060050', 'term': 'Angina, Stable'}, {'id': 'D017202', 'term': 'Myocardial Ischemia'}, {'id': 'D000787', 'term': 'Angina Pectoris'}, {'id': 'D017566', 'term': 'Microvascular Angina'}, {'id': 'D003324', 'term': 'Coronary Artery Disease'}], 'ancestors': [{'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002637', 'term': 'Chest Pain'}, {'id': 'D010146', 'term': 'Pain'}, {'id': 'D009461', 'term': 'Neurologic Manifestations'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D003327', 'term': 'Coronary Disease'}, {'id': 'D001161', 'term': 'Arteriosclerosis'}, {'id': 'D001157', 'term': 'Arterial Occlusive Diseases'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Blood, plasma, buffy coat, PAXgene'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 600}, 'targetDuration': '1 Year', 'patientRegistry': True}, 'statusModule': {'overallStatus': 'ENROLLING_BY_INVITATION', 'startDateStruct': {'date': '2024-09-17', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-12', 'completionDateStruct': {'date': '2028-10-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-02-28', 'studyFirstSubmitDate': '2024-12-24', 'studyFirstSubmitQcDate': '2025-02-28', 'lastUpdatePostDateStruct': {'date': '2025-03-03', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2025-03-03', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-09', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Inflammation', 'timeFrame': 'From enrolment to 12 months', 'description': 'Systemic inflammation may underlie the pathogenesis of resistant angina. Systemic inflammation will be assessed by measurement of the circulating concentration of C-reactive protein.'}, {'measure': 'Glycemic status', 'timeFrame': 'From enrolment to 12 months', 'description': 'Glycemic status may underlie the pathogenesis of resistant angina. Cardiometabolic status will be assessed by measurement of the circulating concentration of glycated hemoglobin (HbA1c), a metabolic biomarker.'}, {'measure': 'Myocardial injury', 'timeFrame': 'From enrolment to 12 months', 'description': 'The circulating concentration of troponin, measured using a high sensitivity assay, reflects ischemic myocardial injury or infarction.'}, {'measure': 'Lipoprotein(a)', 'timeFrame': 'From enrolment to 12 months', 'description': 'Abnormal lipid metabolism, and hyperlipidemia, mediate atherogenesis. The circulating concentrations of lipoprotein(a), a proatherogenic lipid, will be assessed.'}, {'measure': 'Microvascular dysfunction (acetylcholine test population)', 'timeFrame': '24 hours', 'description': 'Microvascular dysfunction is defined as a composite outcome including the occurence of CFR\\<2.5 and/or an IMR\\>=25 and/or microvascular spasm (acetylcholine).\n\nSince acetylcholine-mediated microvascular spasm may reflect microvascular dysfunction, in the subpopulation also undergoing acetylcholine coronary reactivity testing, the microvascular dysfunction outcome measure will include the response to acetylcholine (yes/no), and CFR\\<2.5 and/or IMR\\>=25.'}, {'measure': 'Microvascular blood flow', 'timeFrame': 'From enrolment to 12 months', 'description': 'The ratio of stress subendocardial myocardial blood flow / stress subepicardial myocardial blood flow.\n\nMyocardial blood flow is estimated as ml/min/g myocardial tissue on the American Heart Association model of myocardial segments.'}, {'measure': 'Impaired myocardial blood flow', 'timeFrame': 'From enrolment to 12 months', 'description': 'Extent of impaired hyperemic myocardial blood flow (MBF, ml/min/g), defined as the ordinal number of segments with impaired peak hyperemic myocardial blood flow according to consensus-based, reference thresholds (PMID: 30772231). A regional perfusion defect is defined as myocardial blood flow \\<2.0 ml/min/g in one or more segments. If the perfusion defect is global (rather than regional) and suspected as being due to microvascular disease, then the MBF threshold is \\<2.25 ml/min/g.'}, {'measure': 'Coronary vasomotor dysfunction in response to intracoronary infusion of acetylcholine', 'timeFrame': 'From enrolment to 12 months', 'description': 'Coronary vasomotor dysfunction in response to intracoronary infusion of acetylcholine. Vasomotor dysfunction is defined as coronary artery spasm and/or microvascular spasm according to contemporary diagnostic criteria (PMID: 39210710).'}, {'measure': 'Myocardial blood flow (hyperaemic, global)', 'timeFrame': 'From enrolment to 12 months', 'description': 'Hyperemic myocardial blood flow (MBF, ml/min/g) in all segments.'}], 'primaryOutcomes': [{'measure': 'Residual angina after percutaneous coronary intervention.', 'timeFrame': 'From enrolment to 12 months', 'description': 'Residual angina post-PCI, defined as adjudicated, angina (Seattle Angina Questionnaire Angina Frequency (SAQ-7-AF) score \\<90) occurring within one year of percutaneous coronary intervention.'}], 'secondaryOutcomes': [{'measure': 'Angina', 'timeFrame': 'From enrolment to 12 months', 'description': 'Angina severity will be assessed using the Seattle Angina Questionnaire Summary Score.'}, {'measure': 'Myocardial perfusion reserve', 'timeFrame': 'From enrolment to 12 months', 'description': 'Myocardial perfusion reserve (MPR) within the distribution of the target coronary artery/ies revealed by cardiovascular magnetic resonance (CMR) imaging.'}, {'measure': 'Fractional flow reserve post-percutaneous coronary intervention', 'timeFrame': '24 hours', 'description': 'Fractional flow reserve after percutaneous coronary intervention, reflecting the success of the procedure.'}, {'measure': 'Coronary flow reserve after percutaneous coronary intervention', 'timeFrame': '24 hours', 'description': 'Coronary flow reserve (CFR) post-PCI. Coronary flow reserve takes account of adenosine-mediated vasodilatation of the coronary artery and microcirculation. A CFR \\<2.0 is abnormal, a CFR 2.0-\\<2.5 is impaired and a CFR\\>2.5 is normal.'}, {'measure': 'Index of microvascular resistance after percutaneous coronary intervention', 'timeFrame': '24 hours', 'description': 'Index of microvascular resistance (IMR) post-PCI. IMR reflects adenosine-mediated minimal microvascular resistance. An IMR \\>=25 is abnormal.'}, {'measure': 'Microvascular dysfunction after percutaneous coronary intervention', 'timeFrame': '24 hours', 'description': 'Microvascular dysfunction is defined as a CFR\\<2.5 and/or an IMR\\>=25 post-PCI.'}, {'measure': 'Health-related quality of life', 'timeFrame': 'From enrolment to 12 months', 'description': 'Health-related quality of life will be assessed using the EuroQol-5D 5 Level (5L) questionnaire. EQ-5D-5L is a health status questionnaire that measures five dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression'}, {'measure': 'Physical function', 'timeFrame': 'From enrolment to 12 months', 'description': 'The Duke Activity Status Index (DASI) is a self-administered questionnaire with a 12-item scale that estimates physical functional capacity, cardiorespiratory function and metabolic equivalents (METs).'}, {'measure': 'Illness perception', 'timeFrame': 'From enrolment to 12 months', 'description': 'Brief Illness Perception Questionnaire (BIPQ) is a nine-item scale that measures the cognitive and emotional representations of illness.'}, {'measure': 'Anxiety and depression', 'timeFrame': 'From enrolment to 12 months', 'description': 'Patient Health Questionnaire-4 (PHQ-4) is a self-reported questionnaire to assess for anxiety and depression over the last 2 weeks. Scores are rated as normal (0-2), mild (3-5), moderate (6-8), and severe (9-12). Total score ≥3 for first 2 questions suggests anxiety.'}, {'measure': 'Productivity loss', 'timeFrame': 'From enrolment to 12 months', 'description': 'The Institute for Medical Technology Assessment (iMTA) Productivity Cost Questionnaire (iPCQ) is a generic tool to measure productivity losses.'}, {'measure': 'Fraility', 'timeFrame': 'From enrolment to 12 months', 'description': 'The Rockwood Clinical Frailty Scale (CFS) is a tool to summarize the overall level of fitness or frailty of an older individual.'}, {'measure': 'Serious adverse events', 'timeFrame': 'From enrolment to 12 months', 'description': 'Serious adverse events (SAE) post-enrolment will be assessed using electronic health records without the need for participant contact. The SAE of interest are pre-specified in the protocol. Where e-health records are not an option, then an annual contact with the participant should be undertaken to assess for SAE. The final visit is defined as when the last participant has completed 12 months follow-up. The minimum duration of follow-up will be 12 months and the maximum duration of follow-up is anticipated to be up to 48 months. Longer term follow-up to 20 years will be undertaken using electronic health record linkage.'}, {'measure': 'Low density lipoprotein', 'timeFrame': 'From enrolment to 12 months', 'description': 'Abnormal lipid metabolism, and hyperlipidemia, mediate atherogenesis. The circulating concentrations of low density lipoprotein, a proatherogenic lipid, will be assessed.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Angina', 'Microvascular angina', 'Percutaneous coronary intervention', 'Systems medicine', 'Health economics', 'cohort study', 'coronary artery disease', 'Cardiovascular magnetic resonance imaging', 'Coronary physiology', 'Health-related quality of life', 'Clinical outcomes'], 'conditions': ['Angina (Stable)', 'Ischemic Heart Disease (IHD)']}, 'referencesModule': {'references': [{'pmid': '30608528', 'type': 'BACKGROUND', 'citation': 'Crea F, Bairey Merz CN, Beltrame JF, Berry C, Camici PG, Kaski JC, Ong P, Pepine CJ, Sechtem U, Shimokawa H. Mechanisms and diagnostic evaluation of persistent or recurrent angina following percutaneous coronary revascularization. Eur Heart J. 2019 Aug 1;40(29):2455-2462. doi: 10.1093/eurheartj/ehy857.'}]}, 'descriptionModule': {'briefSummary': 'Angina may persist or recur in patients treated by coronary angioplasty. The angioplasty involves a balloon treatment to open a blocked heart blood vessel and usually a stent (thin metal tube) is placed. Stents do not always improve symptoms and may make symptoms worse. Sometimes a drug-eluting-balloon is used instead of a stent.\n\nThis balloon coats the inside of the blood vessel to prevent re-narrowing. Research is needed to clarify the causes of ongoing angina and its impact on patients and the NHS, and to identify which patients will or will not benefit from a stent (hence avoiding over-treatment in the future).\n\nWe plan a 5-year UK-wide multicenter study involving up to 600 patients with angina undergoing coronary angioplasty (with or without a stent). They will initially have a heart MRI scan. We will assess what might influence the recurrence of angina in the year after the angioplasty procedure. We will measure small blood vessel function in the heart and the amount of plaque persisting after PCI.\n\nPatients who report angina after coronary angioplasty usually have a second invasive angiogram. Instead, we will invite patients to have a heart MRI scan allowing us to also assess whether this scan might be more useful than a repeat angiogram in guiding clinical care. We will collaborate with life scientists, mathematicians, statisticians, and health economists to better understand causes and health economic implications of angina arising after coronary angioplasty procedures.', 'detailedDescription': 'Background: Prior studies indicate that potentially one in three patients may experience angina within 12 months of undergoing percutaneous coronary intervention (PCI).\n\nHypothesis: 1) Diffuse coronary atherosclerosis and/or microvascular dysfunction impair myocardial blood flow (MBF) leading to angina post-PCI.\n\nDesign: A 5-year interdisciplinary program with 3 scientific work-packages (WPs): 1) Clinical, 2) Systems medicine, and 3) Health Economics.\n\nWP1) Cohort study In 4 or more centers in the United Kingdom, 600 patients with angina will undergo stress/rest perfusion cardiovascular magnetic resonance (CMR) imaging with inline pixel-mapping of MBF (ml/min/g) and then coronary physiology measured during PCI. Patient reported outcome measures will be collected routinely during follow-up to 12 months.\n\nPrimary outcome: Adjudicated, residual angina (Seattle Angina Questionnaire Angina Frequency (SAQ-7-AF) score \\<90).\n\nNested case-control study: stress perfusion CMR (MBF culprit artery territory, primary outcome) in approximately 200 patients reporting residual angina and 50 consecutive asymptomatic controls (all post-PCI). Clinically indicated coronary angiography including physiology tests (change from baseline measurement) and acetylcholine testing will be undertaken in approximately 120 patients.\n\nWP2) Systems medicine (n=600) using biostatistics to identify multivariable baseline associates (clinical, coronary physiology, haemodynamics, circulating biomarkers (DNA, RNA, protein) of the SAQ-7-AF score (range 0 (Severe) - 100 (no angina)) post-PCI.\n\nWP3) Health economics of NHS resource utilization and value of information (VoI) modelling to design stratified medicine trials.\n\nValue: Identification of mechanisms to inform downstream diagnostic and therapeutic strategies for angina post-PCI.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Patients with stable angina in whom stress perfusion CMR imaging is reasonable on clinical and/or research grounds and in whom invasive management is plausible or intended will be eligible to participate.', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\nBEFORE INVASIVE MANGEMENT\n\n1. Angina by SAQ-7 Angina Frequency Score \\<90\\*\n2. Stress CMR imaging\\*\n\n DURING INVASIVE MANAGEMENT\n3. PCI (successful)\n4. Coronary physiology assessment post-PCI.\n\nExclusion Criteria:\n\n1. Age \\<=18 years\n2. Acute MI within 30 days\n3. Invasive management \\>90 days after stress CMR\n4. Inability to comply with the protocol\n5. Lack of written informed consent.\n6. Pregnancy.'}, 'identificationModule': {'nctId': 'NCT06854302', 'acronym': 'CorMicA-PCI', 'briefTitle': 'Angina After PCI: a Systems Medicine Study', 'organization': {'class': 'OTHER', 'fullName': 'NHS National Waiting Times Centre Board'}, 'officialTitle': 'Angina After PCI: a Systems Medicine Cohort Study', 'orgStudyIdInfo': {'id': '24/CARD/08'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Patients receiving percutaneous coronary intervention', 'description': 'The study population will include individuals with stable angina who undergo stress perfusion cardiovascular magnetic resonance (CMR) imaging before invasive management.\n\nEligibility will be sequentially assessed. Informed consent will initially be based on angina occurring in patients in whom there is a reasonable expectation for invasive management. Stress CMR imaging should be undertaken on either clinical grounds or for research. Potentially, 700 patients will provide written informed consent. Finally, eligibility will be reassessed during invasive management and eligibility will be confirmed when percutaneous coronary intervention is completed.\n\nThe population will be defined by individuals who fulfil the eligibility criteria. The target sample size is 600 patients with complete data post-PCI. This sample size is anticipated to lead to approximately 200 participants who will report angina consistent with an Seattle Angina Questionnaire Angina Frequency score \\<90.', 'interventionNames': ['Diagnostic Test: Cardiovascular magnetic resonance imaging', 'Diagnostic Test: Coronary physiology']}], 'interventions': [{'name': 'Cardiovascular magnetic resonance imaging', 'type': 'DIAGNOSTIC_TEST', 'description': 'Observational diagnostic tests will include adenosine-stress perfusion cardiovascular magnetic resonance imaging before undergoing percutaneous coronary intervention.', 'armGroupLabels': ['Patients receiving percutaneous coronary intervention']}, {'name': 'Coronary physiology', 'type': 'DIAGNOSTIC_TEST', 'description': 'Invasive coronary function tests using a diagnostic guidewire (PressureWire-X, Abbott), thermodilution, intravenous or intracoronary infusion of adenosine and intracoronary infusions of acetylcholine.', 'armGroupLabels': ['Patients receiving percutaneous coronary intervention']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'CB20AY', 'city': 'Cambridge', 'state': 'Cambridgeshire', 'country': 'United Kingdom', 'facility': 'Royal Papworth Hospital NHS Foundation Trust', 'geoPoint': {'lat': 52.2, 'lon': 0.11667}}, {'zip': 'G814DY', 'city': 'Clydebank', 'state': 'Dunbartonshire', 'country': 'United Kingdom', 'facility': 'Golden Jubilee National Hospital', 'geoPoint': {'lat': 55.90137, 'lon': -4.4057}}, {'zip': 'G75 8RG', 'city': 'East Kilbride', 'state': 'Lanarkshire', 'country': 'United Kingdom', 'facility': 'University Hospital Hairmyres', 'geoPoint': {'lat': 55.76412, 'lon': -4.17669}}, {'zip': 'LS13EX', 'city': 'Leeds', 'state': 'Yorkshire', 'country': 'United Kingdom', 'facility': 'Leeds General Infirmary', 'geoPoint': {'lat': 53.79648, 'lon': -1.54785}}], 'overallOfficials': [{'name': 'Colin Berry, BSc MBChB PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Glasgow'}]}, 'ipdSharingStatementModule': {'infoTypes': ['STUDY_PROTOCOL'], 'timeFrame': 'After the completion of the study', 'ipdSharing': 'YES', 'description': 'IPD will be shared with bone fide research collaborators upon reasonable request with the agreement of the sponsor and chief investigator', 'accessCriteria': 'Bone fide research collaborators by contacting the chief investigator.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'NHS National Waiting Times Centre Board', 'class': 'OTHER'}, 'collaborators': [{'name': 'Robertson Centre for Biostatistics - University of Glasgow', 'class': 'UNKNOWN'}, {'name': 'British Heart Foundation', 'class': 'OTHER'}, {'name': 'Abbott Medical Devices', 'class': 'INDUSTRY'}, {'name': 'CoreAalst BV', 'class': 'INDUSTRY'}, {'name': 'National Heart, Lung, and Blood Institute (NHLBI)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor of Cardiology and Imaging', 'investigatorFullName': 'Colin Berry', 'investigatorAffiliation': 'NHS National Waiting Times Centre Board'}}}}