PROgnostic Value of Precision Medicine in Patients With Myocardial Infarction and Non-obStructive Coronary artEries: the PROMISE Trial.
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 120
- 试验地点
- 3
- 主要终点
- Angina status
研究概览
简要总结
The aim of our study is to evaluate if the use of a precision-medicine approach with a specific therapy tailored on the underlying pathogenic mechanism will improve the quality-of-life in MINOCA patients. The investigators further aim at investigating wherever a precision-medicine approach will improve the prognosis, healthcare related costs, and if that a different profile of plasma biomarkers and microRNAs may serve as diagnostic tools for detecting specific causes of MINOCA and to assess response to therapy. Finally, beyond its pivotal role in differential diagnosis, the investigators hypothesize that cardiac magnetic resonance (CMR) may provide a morphological and functional cardiac characterization as well as help in the prognostic stratification.
详细描述
PROMISE study is a randomized multicenter prospective superiority phase IV trial comparing "precision medicine approach" versus "standard of care" in improving the prognosis and/or the quality-of-life of patients presenting with MINOCA. Patients will be randomized 1:1 to "precision medicine approach" consisting of a comprehensive diagnostic work up aim at elucidating the pathophysiological mechanism of MINOCA and consequently a tailored pharmacological approach versus "standard of care" consisting of standard diagnostic algorithm and therapy for myocardial infarction.
The aim of the study is to evaluate if the use of a precision-medicine approach with a specific therapy tailored on the underlying pathogenic mechanism will improve the quality-of-life in MINOCA patients (primary objective). The investigators further aim at investigating wherever a precision-medicine approach will improve the prognosis, healthcare related costs, and if that a different profile of plasma biomarkers and microRNAs may serve as diagnostic tools for detecting specific causes of MINOCA and to assess response to therapy (secondary objectives). Finally, beyond its pivotal role in differential diagnosis, the investigators hypothesize that cardiac magnetic resonance (CMR) may provide a morphological and functional cardiac characterization as well as help in the prognostic stratification (secondary objective).
The study is a multicentre trial involving 3 centers: IRCCS Fondazione Policlinico Universitario A. Gemelli (Study Promoter), Centro Cardiologico Monzino IRCCS, IRCCS Policlinico San Donato.
It will include 180 patients aged >18 years hospitalized for MINOCA randomized 1:1 to a "precision medicine approach" consisting of a comprehensive diagnostic work-up, analysis of circulating biomarkers and micro RNA expression profile and pharmacological treatment specific for the underlying cause versus a "standard approach" consisting of routine diagnostic work-up and standard medical treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability to give informed consent to the study
- •Age > 18y
- •MINOCA diagnosis, defined as:
- •Acute myocardial infarction (based on Fourth Universal Definition of Myocardial Infarction Criteria):
- •Evidence of non-obstructive coronary artery disease on angiography (i.e., no coronary artery stenosis >50%) in any major epicardial vessel.
- •No specific alternate diagnosis for the clinical presentation (i.e. non-ischemic causes of myocardial injury such as sepsis, pulmonary embolism, and myocarditis).
排除标准
- •Inability or limited capacity to give informed consent to the study
- •Age < 18 y
- •Pregnant and breast-feeding women or patients considering becoming pregnant during the study period will be excluded. For women of childbearing potential, the use of a highly effective contraceptive measure is required in order to be included in the study. "Highly effective contraceptive" is defined in accordance with the recommendations of the Clinical Trial Facilitation Group as a contraceptive measure with a failure rate of less than 1% per year (https://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/2020_09_HMA_CTFG_Contraception_guidance_Version_1.1_updated.pdf).
- •Alternate diagnosis for the clinical presentation (i.e. non-ischemic causes of myocardial injury such as sepsis, pulmonary embolism, valve disease, hypertrophic cardiomyopathy and myocarditis). Also patients presenting with Takotsubo syndrome will be excluded.
- •Contraindication to contrast-enhanced CMR, eg, severe renal dysfunction (glomerular filtration rate <30 mL/min), non-CMR-compatible pacemaker or defibrillator.
- •Contraindication to drugs administrated: e.g a history of hypersensitivity to drugs administrated or its excipients, significant renal and/or hepatic disease.
- •Patients with comorbidities having an expected survival <1-year will be excluded.
研究组 & 干预措施
"Precision medicine approach"
Comprehensive diagnostic work-up with:
- Coronary angiography and ventriculography in all patients
- OCT at the time of coronary angiography in the cath-lab.
- Acetylcholine provocative test (to assess the presence of coronary vasospasm) at the time of coronary angiography in the cath-lab.
- TE-Echo and/or CE-Echo (if distal/microvascular embolization is suspected)
- Blood sampling for circulating biomarkers and miRNA expression profile
- Trans-thoracic echocardiography in all patients during the index hospitalization
- CMR in all cases during the index hospitalization.
Targeted pharmacological treatment specific for the underlying cause:
- DAPT ± stent implantation (if required), statins, beta-blockers, ACEi/ARB (in case of evidence of plaque rupture/erosion)
- CCB and/or nitrates (in case of documentation of coronary vasospasm)
- Anticoagulation (in case of coronary embolism).
干预措施: Nitrates (Drug)
"Standard approach"
Routine diagnostic work-up with:
- Coronary angiography and ventriculography
- Transthoracic echocardiography in all patients during the index hospitalization
- CMR with contrast media only if clinically indicated (i.e. to exclude myocarditis or takotsubo syndrome)
Standard medical treatment with:
- DAPT in all patients
- Beta-blockers (if indicated by the clinical context, i.e. documentation of left ventricular ejection fraction <50%, tachycardia).
- High intensity statins in all patients
- ACEi/ARB (if clinically indicated).
干预措施: Beta blocker (Drug)
"Precision medicine approach"
Comprehensive diagnostic work-up with:
- Coronary angiography and ventriculography in all patients
- OCT at the time of coronary angiography in the cath-lab.
- Acetylcholine provocative test (to assess the presence of coronary vasospasm) at the time of coronary angiography in the cath-lab.
- TE-Echo and/or CE-Echo (if distal/microvascular embolization is suspected)
- Blood sampling for circulating biomarkers and miRNA expression profile
- Trans-thoracic echocardiography in all patients during the index hospitalization
- CMR in all cases during the index hospitalization.
Targeted pharmacological treatment specific for the underlying cause:
- DAPT ± stent implantation (if required), statins, beta-blockers, ACEi/ARB (in case of evidence of plaque rupture/erosion)
- CCB and/or nitrates (in case of documentation of coronary vasospasm)
- Anticoagulation (in case of coronary embolism).
干预措施: Coronary angiography (Procedure)
"Precision medicine approach"
Comprehensive diagnostic work-up with:
- Coronary angiography and ventriculography in all patients
- OCT at the time of coronary angiography in the cath-lab.
- Acetylcholine provocative test (to assess the presence of coronary vasospasm) at the time of coronary angiography in the cath-lab.
- TE-Echo and/or CE-Echo (if distal/microvascular embolization is suspected)
- Blood sampling for circulating biomarkers and miRNA expression profile
- Trans-thoracic echocardiography in all patients during the index hospitalization
- CMR in all cases during the index hospitalization.
Targeted pharmacological treatment specific for the underlying cause:
- DAPT ± stent implantation (if required), statins, beta-blockers, ACEi/ARB (in case of evidence of plaque rupture/erosion)
- CCB and/or nitrates (in case of documentation of coronary vasospasm)
- Anticoagulation (in case of coronary embolism).
干预措施: OCT imaging (Diagnostic Test)
"Precision medicine approach"
Comprehensive diagnostic work-up with:
- Coronary angiography and ventriculography in all patients
- OCT at the time of coronary angiography in the cath-lab.
- Acetylcholine provocative test (to assess the presence of coronary vasospasm) at the time of coronary angiography in the cath-lab.
- TE-Echo and/or CE-Echo (if distal/microvascular embolization is suspected)
- Blood sampling for circulating biomarkers and miRNA expression profile
- Trans-thoracic echocardiography in all patients during the index hospitalization
- CMR in all cases during the index hospitalization.
Targeted pharmacological treatment specific for the underlying cause:
- DAPT ± stent implantation (if required), statins, beta-blockers, ACEi/ARB (in case of evidence of plaque rupture/erosion)
- CCB and/or nitrates (in case of documentation of coronary vasospasm)
- Anticoagulation (in case of coronary embolism).
干预措施: Circulating biomarkers (Diagnostic Test)
"Precision medicine approach"
Comprehensive diagnostic work-up with:
- Coronary angiography and ventriculography in all patients
- OCT at the time of coronary angiography in the cath-lab.
- Acetylcholine provocative test (to assess the presence of coronary vasospasm) at the time of coronary angiography in the cath-lab.
- TE-Echo and/or CE-Echo (if distal/microvascular embolization is suspected)
- Blood sampling for circulating biomarkers and miRNA expression profile
- Trans-thoracic echocardiography in all patients during the index hospitalization
- CMR in all cases during the index hospitalization.
Targeted pharmacological treatment specific for the underlying cause:
- DAPT ± stent implantation (if required), statins, beta-blockers, ACEi/ARB (in case of evidence of plaque rupture/erosion)
- CCB and/or nitrates (in case of documentation of coronary vasospasm)
- Anticoagulation (in case of coronary embolism).
干预措施: Acetylcholine provocative test (Diagnostic Test)
"Precision medicine approach"
Comprehensive diagnostic work-up with:
- Coronary angiography and ventriculography in all patients
- OCT at the time of coronary angiography in the cath-lab.
- Acetylcholine provocative test (to assess the presence of coronary vasospasm) at the time of coronary angiography in the cath-lab.
- TE-Echo and/or CE-Echo (if distal/microvascular embolization is suspected)
- Blood sampling for circulating biomarkers and miRNA expression profile
- Trans-thoracic echocardiography in all patients during the index hospitalization
- CMR in all cases during the index hospitalization.
Targeted pharmacological treatment specific for the underlying cause:
- DAPT ± stent implantation (if required), statins, beta-blockers, ACEi/ARB (in case of evidence of plaque rupture/erosion)
- CCB and/or nitrates (in case of documentation of coronary vasospasm)
- Anticoagulation (in case of coronary embolism).
干预措施: TT-Echocardiography (Diagnostic Test)
"Precision medicine approach"
Comprehensive diagnostic work-up with:
- Coronary angiography and ventriculography in all patients
- OCT at the time of coronary angiography in the cath-lab.
- Acetylcholine provocative test (to assess the presence of coronary vasospasm) at the time of coronary angiography in the cath-lab.
- TE-Echo and/or CE-Echo (if distal/microvascular embolization is suspected)
- Blood sampling for circulating biomarkers and miRNA expression profile
- Trans-thoracic echocardiography in all patients during the index hospitalization
- CMR in all cases during the index hospitalization.
Targeted pharmacological treatment specific for the underlying cause:
- DAPT ± stent implantation (if required), statins, beta-blockers, ACEi/ARB (in case of evidence of plaque rupture/erosion)
- CCB and/or nitrates (in case of documentation of coronary vasospasm)
- Anticoagulation (in case of coronary embolism).
干预措施: TE/contrast echocardiography (Diagnostic Test)
"Precision medicine approach"
Comprehensive diagnostic work-up with:
- Coronary angiography and ventriculography in all patients
- OCT at the time of coronary angiography in the cath-lab.
- Acetylcholine provocative test (to assess the presence of coronary vasospasm) at the time of coronary angiography in the cath-lab.
- TE-Echo and/or CE-Echo (if distal/microvascular embolization is suspected)
- Blood sampling for circulating biomarkers and miRNA expression profile
- Trans-thoracic echocardiography in all patients during the index hospitalization
- CMR in all cases during the index hospitalization.
Targeted pharmacological treatment specific for the underlying cause:
- DAPT ± stent implantation (if required), statins, beta-blockers, ACEi/ARB (in case of evidence of plaque rupture/erosion)
- CCB and/or nitrates (in case of documentation of coronary vasospasm)
- Anticoagulation (in case of coronary embolism).
干预措施: Cardiac magnetic resonance (Diagnostic Test)
"Precision medicine approach"
Comprehensive diagnostic work-up with:
- Coronary angiography and ventriculography in all patients
- OCT at the time of coronary angiography in the cath-lab.
- Acetylcholine provocative test (to assess the presence of coronary vasospasm) at the time of coronary angiography in the cath-lab.
- TE-Echo and/or CE-Echo (if distal/microvascular embolization is suspected)
- Blood sampling for circulating biomarkers and miRNA expression profile
- Trans-thoracic echocardiography in all patients during the index hospitalization
- CMR in all cases during the index hospitalization.
Targeted pharmacological treatment specific for the underlying cause:
- DAPT ± stent implantation (if required), statins, beta-blockers, ACEi/ARB (in case of evidence of plaque rupture/erosion)
- CCB and/or nitrates (in case of documentation of coronary vasospasm)
- Anticoagulation (in case of coronary embolism).
干预措施: Antiplatelet Drug (Drug)
"Precision medicine approach"
Comprehensive diagnostic work-up with:
- Coronary angiography and ventriculography in all patients
- OCT at the time of coronary angiography in the cath-lab.
- Acetylcholine provocative test (to assess the presence of coronary vasospasm) at the time of coronary angiography in the cath-lab.
- TE-Echo and/or CE-Echo (if distal/microvascular embolization is suspected)
- Blood sampling for circulating biomarkers and miRNA expression profile
- Trans-thoracic echocardiography in all patients during the index hospitalization
- CMR in all cases during the index hospitalization.
Targeted pharmacological treatment specific for the underlying cause:
- DAPT ± stent implantation (if required), statins, beta-blockers, ACEi/ARB (in case of evidence of plaque rupture/erosion)
- CCB and/or nitrates (in case of documentation of coronary vasospasm)
- Anticoagulation (in case of coronary embolism).
干预措施: Statin (Drug)
"Precision medicine approach"
Comprehensive diagnostic work-up with:
- Coronary angiography and ventriculography in all patients
- OCT at the time of coronary angiography in the cath-lab.
- Acetylcholine provocative test (to assess the presence of coronary vasospasm) at the time of coronary angiography in the cath-lab.
- TE-Echo and/or CE-Echo (if distal/microvascular embolization is suspected)
- Blood sampling for circulating biomarkers and miRNA expression profile
- Trans-thoracic echocardiography in all patients during the index hospitalization
- CMR in all cases during the index hospitalization.
Targeted pharmacological treatment specific for the underlying cause:
- DAPT ± stent implantation (if required), statins, beta-blockers, ACEi/ARB (in case of evidence of plaque rupture/erosion)
- CCB and/or nitrates (in case of documentation of coronary vasospasm)
- Anticoagulation (in case of coronary embolism).
干预措施: Beta blocker (Drug)
"Precision medicine approach"
Comprehensive diagnostic work-up with:
- Coronary angiography and ventriculography in all patients
- OCT at the time of coronary angiography in the cath-lab.
- Acetylcholine provocative test (to assess the presence of coronary vasospasm) at the time of coronary angiography in the cath-lab.
- TE-Echo and/or CE-Echo (if distal/microvascular embolization is suspected)
- Blood sampling for circulating biomarkers and miRNA expression profile
- Trans-thoracic echocardiography in all patients during the index hospitalization
- CMR in all cases during the index hospitalization.
Targeted pharmacological treatment specific for the underlying cause:
- DAPT ± stent implantation (if required), statins, beta-blockers, ACEi/ARB (in case of evidence of plaque rupture/erosion)
- CCB and/or nitrates (in case of documentation of coronary vasospasm)
- Anticoagulation (in case of coronary embolism).
干预措施: ACEi/ARB (Drug)
"Precision medicine approach"
Comprehensive diagnostic work-up with:
- Coronary angiography and ventriculography in all patients
- OCT at the time of coronary angiography in the cath-lab.
- Acetylcholine provocative test (to assess the presence of coronary vasospasm) at the time of coronary angiography in the cath-lab.
- TE-Echo and/or CE-Echo (if distal/microvascular embolization is suspected)
- Blood sampling for circulating biomarkers and miRNA expression profile
- Trans-thoracic echocardiography in all patients during the index hospitalization
- CMR in all cases during the index hospitalization.
Targeted pharmacological treatment specific for the underlying cause:
- DAPT ± stent implantation (if required), statins, beta-blockers, ACEi/ARB (in case of evidence of plaque rupture/erosion)
- CCB and/or nitrates (in case of documentation of coronary vasospasm)
- Anticoagulation (in case of coronary embolism).
干预措施: CCB (Drug)
"Precision medicine approach"
Comprehensive diagnostic work-up with:
- Coronary angiography and ventriculography in all patients
- OCT at the time of coronary angiography in the cath-lab.
- Acetylcholine provocative test (to assess the presence of coronary vasospasm) at the time of coronary angiography in the cath-lab.
- TE-Echo and/or CE-Echo (if distal/microvascular embolization is suspected)
- Blood sampling for circulating biomarkers and miRNA expression profile
- Trans-thoracic echocardiography in all patients during the index hospitalization
- CMR in all cases during the index hospitalization.
Targeted pharmacological treatment specific for the underlying cause:
- DAPT ± stent implantation (if required), statins, beta-blockers, ACEi/ARB (in case of evidence of plaque rupture/erosion)
- CCB and/or nitrates (in case of documentation of coronary vasospasm)
- Anticoagulation (in case of coronary embolism).
干预措施: Anticoagulant (Drug)
"Standard approach"
Routine diagnostic work-up with:
- Coronary angiography and ventriculography
- Transthoracic echocardiography in all patients during the index hospitalization
- CMR with contrast media only if clinically indicated (i.e. to exclude myocarditis or takotsubo syndrome)
Standard medical treatment with:
- DAPT in all patients
- Beta-blockers (if indicated by the clinical context, i.e. documentation of left ventricular ejection fraction <50%, tachycardia).
- High intensity statins in all patients
- ACEi/ARB (if clinically indicated).
干预措施: Coronary angiography (Procedure)
"Standard approach"
Routine diagnostic work-up with:
- Coronary angiography and ventriculography
- Transthoracic echocardiography in all patients during the index hospitalization
- CMR with contrast media only if clinically indicated (i.e. to exclude myocarditis or takotsubo syndrome)
Standard medical treatment with:
- DAPT in all patients
- Beta-blockers (if indicated by the clinical context, i.e. documentation of left ventricular ejection fraction <50%, tachycardia).
- High intensity statins in all patients
- ACEi/ARB (if clinically indicated).
干预措施: TT-Echocardiography (Diagnostic Test)
"Standard approach"
Routine diagnostic work-up with:
- Coronary angiography and ventriculography
- Transthoracic echocardiography in all patients during the index hospitalization
- CMR with contrast media only if clinically indicated (i.e. to exclude myocarditis or takotsubo syndrome)
Standard medical treatment with:
- DAPT in all patients
- Beta-blockers (if indicated by the clinical context, i.e. documentation of left ventricular ejection fraction <50%, tachycardia).
- High intensity statins in all patients
- ACEi/ARB (if clinically indicated).
干预措施: Cardiac magnetic resonance (Diagnostic Test)
"Standard approach"
Routine diagnostic work-up with:
- Coronary angiography and ventriculography
- Transthoracic echocardiography in all patients during the index hospitalization
- CMR with contrast media only if clinically indicated (i.e. to exclude myocarditis or takotsubo syndrome)
Standard medical treatment with:
- DAPT in all patients
- Beta-blockers (if indicated by the clinical context, i.e. documentation of left ventricular ejection fraction <50%, tachycardia).
- High intensity statins in all patients
- ACEi/ARB (if clinically indicated).
干预措施: Antiplatelet Drug (Drug)
"Standard approach"
Routine diagnostic work-up with:
- Coronary angiography and ventriculography
- Transthoracic echocardiography in all patients during the index hospitalization
- CMR with contrast media only if clinically indicated (i.e. to exclude myocarditis or takotsubo syndrome)
Standard medical treatment with:
- DAPT in all patients
- Beta-blockers (if indicated by the clinical context, i.e. documentation of left ventricular ejection fraction <50%, tachycardia).
- High intensity statins in all patients
- ACEi/ARB (if clinically indicated).
干预措施: Statin (Drug)
"Standard approach"
Routine diagnostic work-up with:
- Coronary angiography and ventriculography
- Transthoracic echocardiography in all patients during the index hospitalization
- CMR with contrast media only if clinically indicated (i.e. to exclude myocarditis or takotsubo syndrome)
Standard medical treatment with:
- DAPT in all patients
- Beta-blockers (if indicated by the clinical context, i.e. documentation of left ventricular ejection fraction <50%, tachycardia).
- High intensity statins in all patients
- ACEi/ARB (if clinically indicated).
干预措施: ACEi/ARB (Drug)
结局指标
主要结局
Angina status
时间窗: 1-year follow-up
Angina status will be evaluated using the single-item "angina stability scale" and the two-item "angina frequence scale" of the Seattle Angina Questionnaire (SAQ). Scores are calculated by summing items within a dimension and transforming it to a 0-100 scale, where 0 is the worst and 100 the best possible level of health. \* To reduce the risk of detection and performance bias, a team of 2 cardiologists blinded to group allocation and belonging to an external cardiology unit will submit and collate the questionnaires from study participants.
eattle Angina Questionnaire (SAQ)
时间窗: 1-year follow-up
Quality of life will be evaluated using the nine-item scale of "physical limitations scale", the three-item "treatment satisfaction scale" and two-item "disease perception scale" of the Seattle Angina Questionnaire (SAQ). Scores are calculated by summing items within a dimension and transforming it to a 0-100 scale, where 0 is the worst and 100 the best possible level of health. \* To reduce the risk of detection and performance bias, a team of 2 cardiologists blinded to group allocation and belonging to an external cardiology unit will submit and collate the questionnaires from study participants.
次要结局
- Rates of major adverse cardiovascular events(1-year follow-up)
- Healthcare primary related-costs(1-year follow-up)
- Ability of different circulating biomarkers as diagnostic biomarker and stratification tool for specific causes of MINOCA.(during index hospitalization (at the time or within 12 hours of coronary angiography))
- Ability of CMR in evaluating different mechanisms of MINOCA and their prognostic value through morphological and functional cardiac characterization.(from day 3 to day 7 from the acute coronary event)
- Healthcare secondary related-costs(1-year follow-up)
研究者
MONTONE ROCCO ANTONIO
Principal Investigator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS