E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with STEMI and NSTEMI treated with PCI and either Bivalirudin (optional to add up to 3000U heparin in lab or up to 5000U given prehospital ) compared to Heparin 70 - 100U/kg alone |
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E.1.1.1 | Medical condition in easily understood language |
Patients with STEMI and NSTEMI treated with PCI and either Bivalirudin (optional to add up to 3000U heparin in lab or up to 5000U given prehospital ) compared to Heparin 70 - 100U/kg alone |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064347 |
E.1.2 | Term | Non ST segment elevation myocardial infarction |
E.1.2 | System Organ Class | 100000004849 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064345 |
E.1.2 | Term | ST segment elevation myocardial infarction |
E.1.2 | System Organ Class | 100000004849 |
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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 |
Compare all cause death, MI, stroke, stent thrombosis and bleeding event in patients with STEMI and NSTEMI treated with PCI and either Bivalirudin 1.75 mg/kg followed by an infusion of 1.75 mg/kg per hour (optional to add up to 3 000 U heparin in lab or up to 5000 U given prehospital) or heparin 70 - 100 U/kg alone
Endpoints at 180 days (primary time point).
- After analysis of interaction, separate analysis of the primary endpoint in the NSTEMI and STEMI groups.
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E.2.2 | Secondary objectives of the trial |
- Time to individual components of the primary end point see above
- The primary end point combined with stroke
- Primary end point in heparin subgroups based on total heparin, U/kg, max ACT.
- TIMI flow grade after PCI.
- Time to re-hospitalization with reinfarction as reported in SWEDEHEART.
- Time to all-cause death or re-hospitalization with myocardial infarction (first occurring).
- Time to target vessel revascularization as reported in SWEDEHEART.
- Time to target lesion revascularization as reported in SWEDEHEART.
- Time to stent thrombosis, time to restenosis, time to re-hospitalization with heart failure as reported in SWEDEHEART.
- Heart failure and complications of PCI during index hospitalization, minor bleeding during index hospitalization as reported in SWEDEHEART
- Length of index hospital stay as reported in SWEDEHEART.
- Bail-out use of GpIIb/IIIa inhibitors during PCI. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Patients with a diagnosis of NSTEMI as judged by the physician in accordance with current guideline definitions (positive troponin) or
patients with a diagnosis of STEMI as defined by chest pain suggestive for myocardial ischemia for at least 30 minutes before hospital admission, time from onset of symptoms of less than 24 hours, and an ECG with new ST-segment elevation in two or more contiguous leads of ≥0.2 mV in leads V2-V3 and/or ≥0.1 mV in other leads or a probable new-onset left bundle branch block.
- PCI of culprit lesion is intended (therapeutic PCI, not primarily diagnostic PCI).
- Ability to provide informed consent
- Age 18 years or older
- Treated with bolus dose of ticagrelor or prasugrel before start of PCI
Age 18 years or older
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E.4 | Principal exclusion criteria |
- Previous randomization in the VALIDATE-SWEDEHEART trial
- Known terminal disease with life expectancy less than one year.
- Patients with known ongoing bleeding
- Patients with uncontrolled hypertension in the opinion of the investigator
- Patients with known subacute bacterial endocarditis
- Patients with known severe renal (GFR < 30 ml/min) and /or liver dysfunctions
- Patients with known thrombocytopenia or thrombocyte function defects
- Any other contraindication for the study medications
- Heparin >5000U before arriving to PCI lab or >3000U given during angiography before randomization
- GpIIb/IIIa-inhibitors have been given or are pre-planned to be given during the procedure.
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E.5 End points |
E.5.1 | Primary end point(s) |
Death, myocardial infarction and major bleeding event in patients at 180 days |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Evaluation of primary endpoints 180 days after the event.
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E.5.2 | Secondary end point(s) |
Main Secondary endpoints:
Endpoints at 180 days (primary time point).
- After analysis of interaction, separate analysis of the primary endpoint in the NSTEMI and STEMI groups.
- Time to individual components of the primary end point (death, myocardial infarction and major bleeding).
- The primary end point combined with stroke as reported in the Swedish national patient registry. (These data will be available with a delay of about a year).
- Primary end point in heparin subgroups based on total heparin, U/kg, max ACT.
- TIMI flow grade after PCI.
- Time to re-hospitalization with reinfarction as reported in SWEDEHEART.
- Time to all-cause death or re-hospitalization with myocardial infarction (first occurring).
- Time to target vessel revascularization as reported in SWEDEHEART.
- Time to target lesion revascularization as reported in SWEDEHEART.
- Time to stent thrombosis as reported in SWEDEHEART.
- Time to restenosis as reported in SWEDEHEART.
- Time to re-hospitalization with heart failure as reported in SWEDEHEART.
- Heart failure and complications of PCI during index hospitalization as reported in SWEDEHEART.
- Minor bleeding during index hospitalization as reported in SWEDEHEART
- Length of index hospital stay as reported in SWEDEHEART.
- Bail-out use of GpIIb/IIIa inhibitors during PCI.
End points at 1 year, 2 years, 3 years, 5 years and 10 years. Annual analyses will be considered confirmatory only if all previous analyses have been significant.
Health Economy
- Economic evaluation based on cost-effectiveness analysis after 180 days with long-term modeling.
- Health related quality of life (HRQOL) measured by Euro-Qol 5D (EQ-5D) using the SEPHIA registry.
- Optional cost-effectiveness analyses at 1 year, 2 years, 3 years, 5 years and 10 years if clinical findings are revised.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 180 days, 1 year, 2 year, 3 year, 5 years and 10 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 | Yes |
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) | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 23 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 8 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |