Myocardial InfarctionPhase 4BRAVE-4NCT00976092
Efficacy Study of Combined Prasugrel and Bivalirudin Versus Clopidogrel and Heparin in Myocardial Infarction
A Phase 4 study testing Prasugrel, Bivalirudin and Clopidogrel in people with Myocardial Infarction, run by Deutsches Herzzentrum Muenchen at 3 sites in Germany.
Trial summary
Randomized comparison of two different anticoagulation strategies: prasugrel plus bivalirudin versus clopidogrel plus heparin in patients with acute myocardial infarction undergoing emergency catheterization and coronary intervention. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myocardial Infarction
- What is being tested?
- Prasugrel, Bivalirudin and Clopidogrel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 548 participants
- Where
- 3 sitesGermany
- Study dates
- Sep 2009to Feb 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients presenting within 24 hours from the onset of symptoms with STEMI
- Informed, written consent
- In women with childbearing potential a pregnancy test is obligatory.
Who cannot join
- Age < 18 years
- Cardiogenic shock
- Active bleeding; bleeding diathesis; coagulopathy
- History of gastrointestinal or genitourinary bleeding <2 months
- Refusal to receive blood transfusion
- Major surgery in the last 6 weeks
Show all 19Show fewer
- History of intracranial bleeding or structural abnormalities
- Suspected aortic dissection
- Heparin-induced thrombocytopenia
- Any previous stroke
- Prior administration of thrombolytics, bivalirudin, low-molecular weight heparin or fondaparinux for the index MI
- Known relevant hematological deviations: Hb <100g/l, Thromb. <100x10^9/l
- Use of coumadin derivatives within the last 7 days
- Chronic therapy with nonsteroidal anti-inflammatory drugs (except aspirin), COX-2 inhibitors, prasugrel
- Known malignancies or other comorbid conditions with life expectancy <1 year
- Known severe liver disease, severe renal failure
- Known allergy to the study medications
- Previous enrollment in this trial
- Pregnancy
Trial locations and contacts
3 sites in 1 country.
Germany3 sites
Herzzentrum der Segeberger Kliniken
Bad Segeberg, 23795
Deutsches Herzzentrum Muenchen
Munich, Bavaria, 80636
Klinikum rechts der Isar, Technische Universitaet Muenchen
Munich, Bavaria, 81674
About this study
Official title: Randomized Trial of Prasugrel Plus Bivalirudin vs. Clopidogrel Plus Heparin in Patients With Acute STEMI
Randomized comparison of two different anticoagulation strategies: prasugrel plus bivalirudin versus clopidogrel plus heparin in patients with acute myocardial infarction undergoing emergency catheterization and coronary intervention.
Read the detailed description
Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion strategy for patients with acute ST-segment elevation myocardial infarction (STEMI). Additional anticoagulation therapy prior or during intervention plays an important role in the short- and long-term outcomes after PPCI. Two separate studies have shown significant benefit against conventional therapy based on clopidogrel and heparin for two recently approved drugs: the direct thrombin inhibitor bivalirudin and the thienopyridine prasugrel. In the HORIZONS-AMI trial, bivalirudin after pretreatment with clopidogrel resulted in improved net clinical outcomes. However, during the first 24 hours after PPCI an increase in the stent thrombosis rate was observed with bivalirudin therapy. Prasugrel has been shown to be superior to clopidogrel in patients with acute coronary syndromes undergoing PCI. The benefit in reduction of ischemic complication was even greater in the subset of patients with STEMI without any increase in the bleeding risk and with a significant reduction in the stent thrombosis rate. Expectedly, the synergic actions of prasugrel and bivalirudin may maximize the benefit of antithrombotic therapy for STEMI patients undergoing PPCI.
- Conditions
- Myocardial Infarction
- Being tested
- Prasugrel, Bivalirudin, Clopidogrel, Heparin
- Keywords
- myocardial infarction, clopidogrel, prasugrel, bivalirudin, primary PCI
- Medical subject headings
- Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PrasugrelDrug
Also called Efient
60 mg prasugrel as loading dose prior to PPCI
BivalirudinDrug
Also called Angiox
IV bolus 0.75 mg/kg of body weight followed by an infusion of 1.75 mg/kg/hour during the PPCI
ClopidogrelDrug
Also called Plavix
600 mg clopidogrel as loading dose before PPCI
HeparinDrug
Also called unfractionated Heparin
i.v. bolus of 70-100 IU/kg body weight
| Study group | Role | What they receive |
|---|---|---|
| Prasugrel + Bivalirudin | Experimental | 60 mg prasugrel plus bivalirudin Receives: Drug: Prasugrel; Drug: Bivalirudin |
| Clopidogrel + Heparin | Active comparator | clopidogrel as loading and heparin Receives: Drug: Clopidogrel; Drug: Heparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
composite of all-cause death, recurrent MI, unplanned IRA revascularization, stroke, definite stent thrombosis or major bleeding
Measured: 30 days
Secondary outcomes (3)
all-cause death, recurrent MI, unplanned IRA-revascularization, stroke or definite stent thrombosis
Measured: 30 days
major bleeding complications
Measured: 30 days
cardiac death
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2009 (estimated)
- Study startSep 2009
- Primary completionFeb 2014 (estimated)
- Study completionFeb 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Myocardial InfarctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 548 participants (actual)
Sponsor and investigators
- Lead sponsor
- Deutsches Herzzentrum Muenchen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Julinda Mehilli, MD, Principal investigator, Deutsches Herzzentrum MuenchenAdnan Kastrati, MD, Study chair, Deutsches Herzzentrum Muenchen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00976092
- Sponsor's protocol ID
- GE IDE I01209
- Acronym
- BRAVE-4
- Status last verified
- Jan 2014
- First submitted
- 11 Sep 2009
- Last updated
- 7 Jan 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Schulz S, Richardt G, Laugwitz KL, Morath T, Neudecker J, Hoppmann P, Mehran R, Gershlick AH, Tolg R, Anette Fiedler K, Abdel-Wahab M, Kufner S, Schneider S, Schunkert H, Ibrahim T, Mehilli J, Kastrati A; Bavarian Reperfusion Alternatives Evaluation (BRAVE) 4 Investigators. Prasugrel plus bivalirudin vs. clopidogrel plus heparin in patients with ST-segment elevation myocardial infarction. Eur Heart J. 2014 Sep 7;35(34):2285-94. doi: 10.1093/eurheartj/ehu182. Epub 2014 May 9.
PubMed 24816809Schulz S, Richardt G, Laugwitz KL, Mehran R, Gershlick AH, Morath T, Mayer K, Neudecker J, Tolg R, Ibrahim T, Hauschke D, Braun D, Schunkert H, Kastrati A, Mehilli J; Bavarian Reperfusion Alternatives Evaluation (BRAVE) 4 Investigators. Comparison of prasugrel and bivalirudin vs clopidogrel and heparin in patients with ST-segment elevation myocardial infarction: Design and rationale of the Bavarian Reperfusion Alternatives Evaluation (BRAVE) 4 trial. Clin Cardiol. 2014 May;37(5):270-6. doi: 10.1002/clc.22268. Epub 2014 Mar 14.
PubMed 24633823
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial of Prasugrel Plus Bivalirudin vs. Clopidogrel Plus Heparin in Patients With Acute STEMI
- ClinicalTrials.gov ID
- NCT00976092
- Acronym / sponsor ID
- BRAVE-4 / GE IDE I01209
- Conditions
- Myocardial Infarction
- Keywords
- myocardial infarction, clopidogrel, prasugrel, bivalirudin, primary PCI
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 548 participants (actual)
- Lead sponsor
- Deutsches Herzzentrum MuenchenUniversity, hospital or other
- Study start
- Sep 2009
- Primary completion
- Feb 2014 (estimated)
- Study completion
- Feb 2015 (estimated)
- First posted
- 14 Sep 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Randomized comparison of two different anticoagulation strategies: prasugrel plus bivalirudin versus clopidogrel plus heparin in patients with acute myocardial infarction undergoing emergency catheterization and coronary intervention.
Detailed description
Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion strategy for patients with acute ST-segment elevation myocardial infarction (STEMI). Additional anticoagulation therapy prior or during intervention plays an important role in the short- and long-term outcomes after PPCI. Two separate studies have shown significant benefit against conventional therapy based on clopidogrel and heparin for two recently approved drugs: the direct thrombin inhibitor bivalirudin and the thienopyridine prasugrel. In the HORIZONS-AMI trial, bivalirudin after pretreatment with clopidogrel resulted in improved net clinical outcomes. However, during the first 24 hours after PPCI an increase in the stent thrombosis rate was observed with bivalirudin therapy. Prasugrel has been shown to be superior to clopidogrel in patients with acute coronary syndromes undergoing PCI. The benefit in reduction of ischemic complication was even greater in the subset of patients with STEMI without any increase in the bleeding risk and with a significant reduction in the stent thrombosis rate. Expectedly, the synergic actions of prasugrel and bivalirudin may maximize the benefit of antithrombotic therapy for STEMI patients undergoing PPCI.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prasugrel + Bivalirudin | Experimental | Drug: Prasugrel, Drug: Bivalirudin60 mg prasugrel plus bivalirudin |
| Clopidogrel + Heparin | Active comparator | Drug: Clopidogrel, Drug: Heparinclopidogrel as loading and heparin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients presenting within 24 hours from the onset of symptoms with STEMI
- Informed, written consent
- In women with childbearing potential a pregnancy test is obligatory.
Key exclusion criteria (19 listed)
- Age < 18 years
- Cardiogenic shock
- Active bleeding; bleeding diathesis; coagulopathy
- History of gastrointestinal or genitourinary bleeding <2 months
- Refusal to receive blood transfusion
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PrasugrelAlso: Efient60 mg prasugrel as loading dose prior to PPCI | Drug | Prasugrel + Bivalirudin |
| BivalirudinAlso: AngioxIV bolus 0.75 mg/kg of body weight followed by an infusion of 1.75 mg/kg/hour during the PPCI | Drug | Prasugrel + Bivalirudin |
| ClopidogrelAlso: Plavix600 mg clopidogrel as loading dose before PPCI | Drug | Clopidogrel + Heparin |
| HeparinAlso: unfractionated Heparini.v. bolus of 70-100 IU/kg body weight | Drug | Clopidogrel + Heparin |
Primary outcome
composite of all-cause death, recurrent MI, unplanned IRA revascularization, stroke, definite stent thrombosis or major bleeding
Time frame: 30 days
3 secondary outcomes
all-cause death, recurrent MI, unplanned IRA-revascularization, stroke or definite stent thrombosis
Time frame: 30 days
major bleeding complications
Time frame: 30 days
cardiac death
Time frame: 30 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2014.
- Derived from this study: PubMed 24816809Schulz S, Richardt G, Laugwitz KL, Morath T, Neudecker J, Hoppmann P, Mehran R, Gershlick AH, Tolg R, Anette Fiedler K, Abdel-Wahab M, Kufner S, Schneider S, Schunkert H, Ibrahim T, Mehilli J, Kastrati A; Bavarian Reperfusion Alternatives Evaluation (BRAVE) 4 Investigators. Prasugrel plus bivalirudin vs. clopidogrel plus heparin in patients with ST-segment elevation myocardial infarction. Eur Heart J. 2014 Sep 7;35(34):2285-94. doi: 10.1093/eurheartj/ehu182. Epub 2014 May 9.
- Derived from this study: PubMed 24633823Schulz S, Richardt G, Laugwitz KL, Mehran R, Gershlick AH, Morath T, Mayer K, Neudecker J, Tolg R, Ibrahim T, Hauschke D, Braun D, Schunkert H, Kastrati A, Mehilli J; Bavarian Reperfusion Alternatives Evaluation (BRAVE) 4 Investigators. Comparison of prasugrel and bivalirudin vs clopidogrel and heparin in patients with ST-segment elevation myocardial infarction: Design and rationale of the Bavarian Reperfusion Alternatives Evaluation (BRAVE) 4 trial. Clin Cardiol. 2014 May;37(5):270-6. doi: 10.1002/clc.22268. Epub 2014 Mar 14.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julinda Mehilli, MD principal investigator
Deutsches Herzzentrum Muenchen
Adnan Kastrati, MD study chair
Deutsches Herzzentrum Muenchen
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Prasugrel, Bivalirudin and Clopidogrel in people with Myocardial Infarction, run by Deutsches Herzzentrum Muenchen at 3 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
composite of all-cause death, recurrent MI, unplanned IRA revascularization, stroke, definite stent thrombosis or major bleeding (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00976092, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2014.