Clinical trial NCT02311231: Bivalirudin vs Heparin in NSTEMI and STEMI in Patients on Modern Antiplatelet Therapy in SWEDEHEART
Official title: Bivalirudin vs Heparin in NSTEMI and STEMI in Patients on Modern Antiplatelet Therapy in SWEDEHEART A Multicenter, Prospective, Randomized Controlled Clinical Trial Based on the SWEDEHEART Platform
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: ST-segment Elevation Myocardial Infarction
Non ST-segment Elevation Myocardial Infarction
Lead sponsor: Uppsala University
Sponsor class: OTHER
Collaborators: name: Lund University
First posted: 2014-12-08
Enrollment: 6012
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In this trial we test the hypothesis that PCI and bivalirudin is superior to heparin alone (according to local protocol) in reducing death, MI, and major bleeding in patients with NSTEMI or STEMI at 180 days (primary end point), treated with ticagrelor or prasugrel.

Detailed description: The follow up of endpoints will be performed using SWEDEHEART and national registries. Follow up of primary endpoints and stroke will also be performed by telephone contacts with the patients or first degree relatives by a nurse phone call after 7 days and 180 days. The nurses will also accumulate hospital record information on these endpoints.

A central adjudication will be performed for all reported primary endpoints for the first 180 days follow up. Every site will prepare source documents for the event and send it to UCR for central adjudication by an independent committee.

Eligibility criteria: 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).
* Treated with bolus dose of ticagrelor or prasugrel before start of PCI. See 2.6
* Ability to provide informed consent
* Age 18 years or older

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 dysfunction
* Patients with known thrombocytopenia or thrombocyte function defects
* Any other contraindication for the study medications.
* Heparin \> 5000U Before arriving to PCI lab or \> 3000 U given during angiography before randomization.
* GpIIb/IIIa inhibitors have been given or are pre-planned to be given during the procedure.

Primary outcomes:
measure: Death, Myocardial infarction and major bleeding event
timeFrame: 180 days
Secondary outcomes:
measure: Death, Myocardial infarction and major bleeding events in the subgroups NSTEMI and STEMI
timeFrame: 180 days
measure: Time to primary endpoints (death, myocardial infarction and major bleeding event)
timeFrame: 180 days
measure: Number of events where primary endpoints (death, myocardial infarction and major bleeding event) and stroke have been registered
timeFrame: 180 days
measure: Number of events where primary endpoints (death, myocardial infarction and major bleeding event) have been registered in heparin subgroups (U/kg, groups with certain max ACT values etc)
timeFrame: 180 days
measure: TIMI flow grade after PCI
timeFrame: 180 days
measure: Time to re-hospitalization with reinfarction
timeFrame: 180 days
measure: Time to all-cause death or re-hospitalization with myocardial infarction
timeFrame: 180 days
measure: Time to target vessel revascularization
timeFrame: 180 days
measure: Time to target lesion revascularization
timeFrame: 180 days
measure: Time to stent thrombosis
timeFrame: 180 days
measure: Time to restenosis
timeFrame: 180 days
measure: Time to re-hospitalization with heart failure
timeFrame: 180 days
measure: Heart failure and complications of PCI during index hospitalization
timeFrame: 180 days
measure: Minor bleeding during index hospitalization
timeFrame: 180 days
measure: Length of index hospital stay
timeFrame: 180 days
measure: Bail-out use of GpIIb/IIIa
timeFrame: 180 days
Other outcomes:
Locations:
city: Lund
country: Sweden
facility: Lund University
Study officials:
affiliation: Lund University, Lund, Sweden
name: David Erlinge
role: PRINCIPAL_INVESTIGATOR
References:
citation: James S, Koul S, Andersson J, Angeras O, Bhiladvala P, Calais F, Danielewicz M, Frobert O, Grimfjard P, Gotberg M, Henareh L, Ioanes D, Jensen J, Linder R, Lindroos P, Omerovic E, Panayi G, Ramunddal T, Sarno G, Ulvenstam A, Voltz S, Wagner H, Wikstrom H, Ostlund O, Erlinge D. Bivalirudin Versus Heparin Monotherapy in ST-Segment-Elevation Myocardial Infarction. Circ Cardiovasc Interv. 2021 Dec;14(12):e008969. doi: 10.1161/CIRCINTERVENTIONS.120.008969. Epub 2021 Dec 14.
citation: Bergman S, Mohammad MA, James SK, Angeras O, Wagner H, Jensen J, Schersten F, Frobert O, Koul S, Erlinge D. Clinical Impact of Intraprocedural Stent Thrombosis During Percutaneous Coronary Intervention in Patients Treated With Potent P2Y12 inhibitors - a VALIDATE-SWEDEHEART Substudy. J Am Heart Assoc. 2021 Sep 21;10(18):e022984. doi: 10.1161/JAHA.121.022984. Epub 2021 Sep 13.
citation: Rylance RT, Wagner P, Omerovic E, Held C, James S, Koul S, Erlinge D. Assessing the external validity of the VALIDATE-SWEDEHEART trial. Clin Trials. 2021 Aug;18(4):427-435. doi: 10.1177/17407745211012438. Epub 2021 May 20.
citation: Jamaly S, Redfors B, Omerovic E, Carlsson L, Karason K. Prognostic significance of BMI after PCI treatment in ST-elevation myocardial infarction: a cohort study from the Swedish Coronary Angiography and Angioplasty Registry. Open Heart. 2021 Feb;8(1):e001479. doi: 10.1136/openhrt-2020-001479.
citation: Olsson A, Ring C, Josefsson J, Eriksson A, Rylance R, Frobert O, James S, Sparv D, Erlinge D. Patient experience of the informed consent process during acute myocardial infarction: a sub-study of the VALIDATE-SWEDEHEART trial. Trials. 2020 Mar 6;21(1):246. doi: 10.1186/s13063-020-4147-0.
citation: Wester A, Attar R, Mohammad MA, Andell P, Hofmann R, Jensen J, Szummer K, Erlinge D, Koul S. Impact of Baseline Anemia in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: A Prespecified Analysis From the VALIDATE-SWEDEHEART Trial. J Am Heart Assoc. 2019 Aug 20;8(16):e012741. doi: 10.1161/JAHA.119.012741. Epub 2019 Aug 7.
citation: Erlinge D, Omerovic E, Frobert O, Linder R, Danielewicz M, Hamid M, Swahn E, Henareh L, Wagner H, Hardhammar P, Sjogren I, Stewart J, Grimfjard P, Jensen J, Aasa M, Robertsson L, Lindroos P, Haupt J, Wikstrom H, Ulvenstam A, Bhiladvala P, Lindvall B, Lundin A, Todt T, Ioanes D, Ramunddal T, Kellerth T, Zagozdzon L, Gotberg M, Andersson J, Angeras O, Ostlund O, Lagerqvist B, Held C, Wallentin L, Schersten F, Eriksson P, Koul S, James S. Bivalirudin versus Heparin Monotherapy in Myocardial Infarction. N Engl J Med. 2017 Sep 21;377(12):1132-1142. doi: 10.1056/NEJMoa1706443. Epub 2017 Aug 27.