E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
ST segment elevation myocardial infarction |
ST-nousuinfarktin sairastaneet potilaat |
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E.1.1.1 | Medical condition in easily understood language |
Patients which hade had ST segment elevation myocardial infarction |
ST-nousuinfarktin sairastaneet potilaat |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
In patients with STEMI who have undergone PCI, the primary objectives of this study is to determine: 1. If colchicine can reduce the incidence of cardiovascular (CV) death, myocardial infarction (MI), or stroke over duration of follow-up. 2. If spironolactone can reduce the incidence of CV death or new or worsening heart failure over duration of follow-up. 3. The rate of major adverse cardiac events (MACE) in patients who have received a SYNERGY everolimus-eluting stent compared to performance goal. |
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E.2.2 | Secondary objectives of the trial |
1. Colchicine vs. placebo: Time-to-event of the composite of cardiovascular death, recurrent MI, unplanned ischemia driven revascularization, or stroke, over the duration of follow-up. 2. Spironolactone vs. placebo: a) Time-to-event of cardiovascular death over the duration of follow-up. b) time-to-event of the composite of cardiovascular death, new or worsening heart failure or significant ventricular arrhythmia over the duration of follow-up. 3. Combined colchicine and spironolactone: Time to event for the composite of cardiovascular death, recurrent MI, stroke or new or worsening heart failure over follow up. 4. SYNERGY stent: Incidence of Definite Stent Thrombosis within 1 year |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. a) Patients with STEMI referred for PCI within 12 hours of symptom onset, have a culprit lesion amenable to stenting, and with planned SYNERGY stent implantation for SYNERGY registry OR b) Patients with STEMI referred for PCI within 24 hours of symptom onset, not prospectively enrolled in SYNERGY STENT registry 2. Able to be randomized within 48 hours of index PCI and during initial hospitalization (however patients should be randomized as soon as possible after PCI) 3. Written informed consent |
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E.4 | Principal exclusion criteria |
- Age ≤18 years - Pregnancy, breastfeeding, or women of childbaring potential who are not using an effective method of contraception - Any medical, geographic, or social factor making study participation impractical or precluding required folow-up - Systolic blood pressure <90 mm Hg - Active diarrhea - Known allergy or contraindication to everolimus, the Synergy stent or any of its components - Unable to receive dual antiplatelet therapy - Any contraindication or known intolerance to colchicine or spironolactone - Requirement of cholchicine or mineralocorticoid antagonist for another indication - History of cirrhosis or current severe hepatic disease - Current or planned use of any of: cyclosporine, verapamil, HIV protease inbibitors, azole antifungals, or macrolide antibiotics - Creatinine clearance <30 ml/min/1.73m2 - Serum Potassium >5.0 mew/L |
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E.5 End points |
E.5.1 | Primary end point(s) |
In patients with STEMI who have undergone PCI, the primary objectives of this study is to determine: 1. Colchicine vs. placebo: time to event of the composite of CV death, recurrent MI, or stroke over duration of follow-up. 2. Spironolactone vs. placebo: time to event of the composite of CV death or new or worsening heart failure over duration of follow-up. 3. SYNERGY stent: MACE (defined as the composite of CV death, recurrent MI, or unplanned ischemia driven target vessel revascularization) for SYNERGY stent compared to a historical performance goal within 1 year |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time-to-event over duration of follow-up. Minimum follow-up of 1 year to maximum of 3 years (average of 2 years). |
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E.5.2 | Secondary end point(s) |
1. COLCHINE VS. COLCHICINE-PLACEBO: Time-to-event of the composite of cardiovascular death, recurrent MI, unplanned ischemia driven revascularization, or stroke, over the duration of follow-up. 2. SPIRONOLACTONE VS. SPIRONOLACTONE-PLACEBO: a) Time-to-event of cardiovascular death over the duration of follow-up. b) Time-to-event of the composite of cardiovascular death, new or worsening heart failure or significant ventricular arrhythmia over the duration of follow-up. 3. COMBINED COLCHICINE AND SPIRONOLACTONE: Time to event for the composite of cardiovascular death, recurrent MI, stroke or new or worsening heart failure over follow up 4. SYNERGY STENT REGISTRY: Incidence of Definite Stent Thrombosis within 1 year. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Time-to-event over duration of follow-up. Minimum follow-up of 1 year to maximum of 3 years (average of 2 years). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |