Cardiovascular DiseasesPhase 4CompareCrushNCT03296540
CRUSHed vs. Uncrushed Prasugrel in STEMI Patients Undergoing PCI
A Phase 4 study testing Prasugrel (Crushed tablets) and Prasugrel (Integral tablets) in people with Cardiovascular Diseases, run by Maasstad Hospital at 2 sites in Netherlands.
Trial summary
The studys evaluates the effect of prehospital administration of crushed tablets of Prasugrel loading dose (in addition to ASA and standard care) versus uncrushed tablets of Prasugrel loading dose on efficacy and safety as well as pharmacodynamics as measured by platelet reactivity using VerifyNow. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiovascular Diseases
- What is being tested?
- Prasugrel (Crushed tablets) and Prasugrel (Integral tablets)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 729 participants
- Where
- 2 sitesNetherlands
- Study dates
- 28 Nov 2017to 1 May 2021
- 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
- Consecutive patients with STEMI planned for primary PCI:
- Deferred written informed consent within 4 hours after prasugrel loading dose
- Adult men and women aged at least 18 years
- Symptoms of acute MI of more than 30 min but less than 6 hours
- New persistent ST-segment elevation ≥ 1 mm in two or more contiguous ECG leads
Who cannot join
- Contraindication to prasugrel (e.g., hypersensitivity, active bleeding, history of previous intracranial bleed, history of any CVA including TIA, moderate to severe hepatic impairment, GI bleed within the past 6 months, major surgery within past 4 weeks)
- Patient who has received loading dose of clopidogrel or ticagrelor for the index event or are on chronic treatment of ticagrelor, or prasugrel. However, patients on maintenance dose clopidogrel for at least 7 days are included in the study (see appendix A).
- Oral anticoagulation therapy that cannot be stopped (i.e. patients requiring chronic therapy)
- Planned fibrinolytic treatment
- Patient requiring dialysis
- Known, clinically important thrombocytopenia
Show all 13Show fewer
- Known clinically important anaemia
- Known pregnancy or lactation
- Need for a concomitant systemic therapy with strong inhibitors or strong inducers of CYP3A
- Condition which may either put the patient at risk or influence the result of the study (e.g., cardiogenic shock with severe hemodynamic instability, active cancer, risk for non-compliance, risk for being lost to follow up)
- Patient unable to swallow oral medication (i.e. intubated patients)
- Patient who have not received prasugrel loading dose in the ambulance
- Patient who vomited after randomization / receiving the loading dose prasugrel
Trial locations and contacts
2 sites in 1 country.
Netherlands2 sites
Erasmus Medical Center
Rotterdam, 3015 CE
Maasstadziekenhuis
Rotterdam, 3079 DZ
About this study
Official title: COMPARison of Pre-hospital CRUSHed vs. Uncrushed Prasugrel Tablets in Patients With STEMI Undergoing Primary Percutaneous Coronary Interventions
The studys evaluates the effect of prehospital administration of crushed tablets of Prasugrel loading dose (in addition to ASA and standard care) versus uncrushed tablets of Prasugrel loading dose on efficacy and safety as well as pharmacodynamics as measured by platelet reactivity using VerifyNow.
Read the detailed description
The study is a two-centre, randomized, 1:1 trial comparing prehospital prasugrel initiation therapy between crushed vs. uncrushed prasugrel tablets on efficacy and safety as well as pharmacodynamics in STEMI patients.
Patients with STEMI planned for primary PCI will be screened and, if inclusion criteria are met, included at first medical contact (paramedics). After enrolment, patients will be randomly assigned (1:1) to receive 60mg prasugrel loading dose by ingesting integral or crushed tablets.
The follow-up duration is 12 months, i.e. clinical outcomes will be analysed in-hospital, at 30 days, and 12 months
- Conditions
- Cardiovascular Diseases
- Being tested
- Prasugrel (Crushed tablets), Prasugrel (Integral tablets)
- Keywords
- STEMI
- Medical subject headings
- Cardiovascular Diseases, ST Elevation Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prasugrel (Crushed tablets)Drug
Also called 6 Crushed tablets of Prasugrel 10mg
loading dose of 6 crushed tablets 10mg Prasugrel
Prasugrel (Integral tablets)Drug
Also called 6 Integral tablets of Prasugrel 10mg
loading dose of 6 integral tablets of 10mg Prasugrel
| Study group | Role | What they receive |
|---|---|---|
| Uncrushed | Active comparator | 6 Integral tablets Prasugrel as loading dose Receives: Drug: Prasugrel (Integral tablets) |
| Crushed | Experimental | 6 Crushed tablets Prasugrel as loading dose Receives: Drug: Prasugrel (Crushed tablets) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Co-primary endpoint is the percentage of patients reaching TIMI flow grade 3 of MI culprit vessel at initial angiography or a ≥70% ST-segment resolution directly post-PCI
To assess the efficacy of crushed vs. integral tablets of prasugrel loading dose treatment by comparing the percentage of patients reaching the co-primary endpoint of TIMI flow grade 3 of MI culprit vessel at initial angiography or a ≥70% ST-segment elevation resolution directly post-PCI.
Measured: directly post PCI
Secondary outcomes (16)
Composite of death, MI, stroke, urgent revascularization and acute stent thrombosis in hospital, at 30 days and 12 months
Percentage of patients in the following: composite of death, MI, stroke, urgent revascularization and acute stent thrombosis during inhospital stay, 30 days and 12 months of study
Measured: upto 72 hours after randomisation, at 30 days and 12 months.
Composite of death, MI, urgent revascularization during inhospital, at 30 days and 12 months of study
Percentage of patients in the following: composite of death, MI, or urgent revascularization during inhospital, 30 days and 12 months of study
Measured: 30 days and 12 months
Individual endpoints during inhospital, at 30 days and 12 months of study
Percentage of patients presenting with any of the individual endpoints during inhospital, 30 days and 12 months of study
Measured: upto 72 hours after randomisation, at 30 days and 12 months.
Thrombotic bail-out with GPIIb/IIIa inhibitors at initial PCI
Percentage of patients receiving thrombotic bail-out with GPIIb/IIIa inhibitors at initial PCI
Measured: directly post PCI
Complete (≥ 70%) ST-segment elevation resolution pre-PCI and 60 min post-PCI
Complete (≥ 70%) ST-segment elevation resolution pre-PCI and 60 min post-PCI
Measured: pre-PCI and 60 min post-PCI
Corrected TIMI frame count (cTFC) at angiography, pre and post PCI.
Corrected TIMI frame count (cTFC) at angiography, pre and post PCI
Measured: pre PCI, directly post PCI
TIMI myocardial perfusion grade (TMPG) at angiography, pre and post PCI.
TIMI myocardial perfusion grade (TMPG) at angiography, pre and post PCI.
Measured: pre PCI, directly post PCI
Time-relationship (from symptom onset to 1st dose intake) on each co-primary
Time from symptom onset to 1st dose intake correlated to TIMI flow grade 3 of MI culprit vessel at initial angiography and on ≥70% ST-segment elevation resolution directly post-PCI
Measured: directly post-PCI
Time-relationship (from 1st dose intake to ECG/ angiography) on each co-primary
Time from first dose intake to ECG correlated to ≥70% ST-segment elevation resolution directly post-PCI and time from randomization to initial angiography correlated to TIMI flow grade 3 of MI culprit vessel
Measured: directly post-PCI
TIMI flow grade 3 at end of procedure.
TIMI flow grade 3 at end of procedure.
Measured: directly post PCI
Myocardial Blush at the start and end of the procedure
Myocardial Blush at the start and end of the procedure
Measured: pre PCI, directly post PCI
Maximum CK, and CK-MB levels
Maximum CK, and CK-MB levels
Measured: upto 72 hours after randomisation
Level of platelet inhibition at first medical contact, beginning and end of PCI procedure, as well as at 4 hours after prasugrel administration
Level of platelet inhibition at first medical contact, beginning and end of PCI procedure, as well as at 4 hours after prasugrel administration
Measured: at time of prasugrel administration, pre PCI, directly post PCI, 4 hours after prasugrel administration
Platelet reactivity, at each time point as well as over time
PRU measurements at first medical contact, beginning and end of PCI, as well as 4hours after drug administration
Measured: at time of prasugrel administration, pre PCI, directly post PCI, 4 hours after prasugrel administration
Rates of HPR
Percentage of patients with PRU values over HPR threshold
Measured: upto 72 hours after randomisation
Exploratory analyses within each group to evaluate any differences in PD among patients receiving morphine
PD of each group among patients stratified for morphine treatment
Measured: upto 72 hours after randomisation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2017
- Study start28 Nov 2017
- Primary completion1 May 2021
- Study completion1 May 2021
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 Cardiovascular DiseasesStudies 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
- Model description
- Crushed versus uncrushed tablets Prasugrel loading dose
- Masking
- None (open label)
- Enrolment
- 729 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maasstad Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- MicroPort Orthopedics Inc., Daiichi Sankyo, Research Maatschap Cardiologen Rotterdam Zuid
- Responsible party
- Sponsor
- Investigators
- George Vlachojannis, MD, PhD, Principal investigator, MaasstadziekenhuisPieter C Smits, MD, PhD, Study director, MaasstadziekenhuisNicolas van Mieghem, MD, PhD, Study chair, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03296540
- Sponsor's protocol ID
- 2017-40
- Acronym
- CompareCrush
- Status last verified
- May 2021
- First submitted
- 6 Sep 2017
- Last updated
- 7 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Vlachojannis GJ, Wilschut JM, Vogel RF, Lemmert ME, Delewi R, Diletti R, van der Waarden NWPL, Nuis RJ, Paradies V, Alexopoulos D, Zijlstra F, Montalescot G, Angiolillo DJ, Krucoff MW, Van Mieghem NM, Smits PC. Effect of Prehospital Crushed Prasugrel Tablets in Patients With ST-Segment-Elevation Myocardial Infarction Planned for Primary Percutaneous Coronary Intervention: The Randomized COMPARE CRUSH Trial. Circulation. 2020 Dec 15;142(24):2316-2328. doi: 10.1161/CIRCULATIONAHA.120.051532. Epub 2020 Oct 14.
PubMed 33315489Vlachojannis GJ, Vogel RF, Wilschut JM, Lemmert ME, Delewi R, Diletti R, van Vliet R, van der Waarden N, Nuis RJ, Paradies V, Alexopoulos D, Zijlstra F, Montalescot G, Angiolillo DJ, Krucoff MW, Van Mieghem NM, Smits PC. COMPARison of pre-hospital CRUSHed vs. uncrushed Prasugrel tablets in patients with STEMI undergoing primary percutaneous coronary interventions: Rationale and design of the COMPARE CRUSH trial. Am Heart J. 2020 Jun;224:10-16. doi: 10.1016/j.ahj.2020.03.005. Epub 2020 Mar 11.
PubMed 32272255
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- COMPARison of Pre-hospital CRUSHed vs. Uncrushed Prasugrel Tablets in Patients With STEMI Undergoing Primary Percutaneous Coronary Interventions
- ClinicalTrials.gov ID
- NCT03296540
- Acronym / sponsor ID
- CompareCrush / 2017-40
- Conditions
- Cardiovascular Diseases
- Keywords
- STEMI
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 729 participants (actual)
- Lead sponsor
- Maasstad HospitalUniversity, hospital or other
- Collaborators
- MicroPort Orthopedics Inc., Daiichi Sankyo, Research Maatschap Cardiologen Rotterdam Zuid
- Study start
- 28 Nov 2017 (actual)
- Primary completion
- 1 May 2021 (actual)
- Study completion
- 1 May 2021 (actual)
- First posted
- 28 Sep 2017 (actual)
- 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.
The studys evaluates the effect of prehospital administration of crushed tablets of Prasugrel loading dose (in addition to ASA and standard care) versus uncrushed tablets of Prasugrel loading dose on efficacy and safety as well as pharmacodynamics as measured by platelet reactivity using VerifyNow.
Detailed description
The study is a two-centre, randomized, 1:1 trial comparing prehospital prasugrel initiation therapy between crushed vs. uncrushed prasugrel tablets on efficacy and safety as well as pharmacodynamics in STEMI patients.
Patients with STEMI planned for primary PCI will be screened and, if inclusion criteria are met, included at first medical contact (paramedics). After enrolment, patients will be randomly assigned (1:1) to receive 60mg prasugrel loading dose by ingesting integral or crushed tablets.
The follow-up duration is 12 months, i.e. clinical outcomes will be analysed in-hospital, at 30 days, and 12 months
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Crushed versus uncrushed tablets Prasugrel loading dose
| Arm | Type | Receives |
|---|---|---|
| Uncrushed | Active comparator | Drug: Prasugrel (Integral tablets)6 Integral tablets Prasugrel as loading dose |
| Crushed | Experimental | Drug: Prasugrel (Crushed tablets)6 Crushed tablets Prasugrel as loading dose |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Deferred written informed consent within 4 hours after prasugrel loading dose
- Adult men and women aged at least 18 years
- Symptoms of acute MI of more than 30 min but less than 6 hours
- New persistent ST-segment elevation ≥ 1 mm in two or more contiguous ECG leads
Key exclusion criteria (13 listed)
- Contraindication to prasugrel (e.g., hypersensitivity, active bleeding, history of previous intracranial bleed, history of any CVA including TIA, moderate to severe hepatic impairment, GI bleed within the past 6 months, major surgery within past 4 weeks)
- Patient who has received loading dose of clopidogrel or ticagrelor for the index event or are on chronic treatment of ticagrelor, or prasugrel. However, patients on maintenance dose clopidogrel for at least 7 days are included in the study (see appendix A).
- Oral anticoagulation therapy that cannot be stopped (i.e. patients requiring chronic therapy)
- Planned fibrinolytic treatment
- Patient requiring dialysis
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 |
|---|---|---|
| Prasugrel (Crushed tablets)Also: 6 Crushed tablets of Prasugrel 10mgloading dose of 6 crushed tablets 10mg Prasugrel | Drug | Crushed |
| Prasugrel (Integral tablets)Also: 6 Integral tablets of Prasugrel 10mgloading dose of 6 integral tablets of 10mg Prasugrel | Drug | Uncrushed |
Primary outcome
Co-primary endpoint is the percentage of patients reaching TIMI flow grade 3 of MI culprit vessel at initial angiography or a ≥70% ST-segment resolution directly post-PCI
Time frame: directly post PCI
To assess the efficacy of crushed vs. integral tablets of prasugrel loading dose treatment by comparing the percentage of patients reaching the co-primary endpoint of TIMI flow grade 3 of MI culprit vessel at initial angiography or a ≥70% ST-segment elevation resolution directly post-PCI.
16 secondary outcomes
Composite of death, MI, stroke, urgent revascularization and acute stent thrombosis in hospital, at 30 days and 12 months
Time frame: upto 72 hours after randomisation, at 30 days and 12 months.
Composite of death, MI, urgent revascularization during inhospital, at 30 days and 12 months of study
Time frame: 30 days and 12 months
Individual endpoints during inhospital, at 30 days and 12 months of study
Time frame: upto 72 hours after randomisation, at 30 days and 12 months.
Thrombotic bail-out with GPIIb/IIIa inhibitors at initial PCI
Time frame: directly post PCI
Complete (≥ 70%) ST-segment elevation resolution pre-PCI and 60 min post-PCI
Time frame: pre-PCI and 60 min post-PCI
Corrected TIMI frame count (cTFC) at angiography, pre and post PCI.
Time frame: pre PCI, directly post PCI
TIMI myocardial perfusion grade (TMPG) at angiography, pre and post PCI.
Time frame: pre PCI, directly post PCI
Time-relationship (from symptom onset to 1st dose intake) on each co-primary
Time frame: directly post-PCI
Time-relationship (from 1st dose intake to ECG/ angiography) on each co-primary
Time frame: directly post-PCI
TIMI flow grade 3 at end of procedure.
Time frame: directly post PCI
Myocardial Blush at the start and end of the procedure
Time frame: pre PCI, directly post PCI
Maximum CK, and CK-MB levels
Time frame: upto 72 hours after randomisation
Level of platelet inhibition at first medical contact, beginning and end of PCI procedure, as well as at 4 hours after prasugrel administration
Time frame: at time of prasugrel administration, pre PCI, directly post PCI, 4 hours after prasugrel administration
Platelet reactivity, at each time point as well as over time
Time frame: at time of prasugrel administration, pre PCI, directly post PCI, 4 hours after prasugrel administration
Rates of HPR
Time frame: upto 72 hours after randomisation
Exploratory analyses within each group to evaluate any differences in PD among patients receiving morphine
Time frame: upto 72 hours after randomisation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2021.
- Derived from this study: PubMed 33315489Vlachojannis GJ, Wilschut JM, Vogel RF, Lemmert ME, Delewi R, Diletti R, van der Waarden NWPL, Nuis RJ, Paradies V, Alexopoulos D, Zijlstra F, Montalescot G, Angiolillo DJ, Krucoff MW, Van Mieghem NM, Smits PC. Effect of Prehospital Crushed Prasugrel Tablets in Patients With ST-Segment-Elevation Myocardial Infarction Planned for Primary Percutaneous Coronary Intervention: The Randomized COMPARE CRUSH Trial. Circulation. 2020 Dec 15;142(24):2316-2328. doi: 10.1161/CIRCULATIONAHA.120.051532. Epub 2020 Oct 14.
- Derived from this study: PubMed 32272255Vlachojannis GJ, Vogel RF, Wilschut JM, Lemmert ME, Delewi R, Diletti R, van Vliet R, van der Waarden N, Nuis RJ, Paradies V, Alexopoulos D, Zijlstra F, Montalescot G, Angiolillo DJ, Krucoff MW, Van Mieghem NM, Smits PC. COMPARison of pre-hospital CRUSHed vs. uncrushed Prasugrel tablets in patients with STEMI undergoing primary percutaneous coronary interventions: Rationale and design of the COMPARE CRUSH trial. Am Heart J. 2020 Jun;224:10-16. doi: 10.1016/j.ahj.2020.03.005. Epub 2020 Mar 11.
- Individual participant dataSharing planned: No
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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.
George Vlachojannis, MD, PhD principal investigator
Maasstadziekenhuis
Pieter C Smits, MD, PhD study director
Maasstadziekenhuis
Nicolas van Mieghem, MD, PhD study chair
Erasmus Medical Center
2 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 (Crushed tablets) and Prasugrel (Integral tablets) in people with Cardiovascular Diseases, run by Maasstad Hospital at 2 sites in Netherlands.
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 5 inclusion and 13 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: finished, as of the sponsor's last update on 7 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Co-primary endpoint is the percentage of patients reaching TIMI flow grade 3 of MI culprit vessel at initial angiography or a ≥70% ST-segment resolution directly post-PCI (time frame: directly post PCI). 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 NCT03296540, 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 May 2021.