ST Segment Elevation Myocardial InfarctionPhase 4CANTICNCT03247738
Platelet Inhibition With Cangrelor and Crushed Ticagrelor in STEMI
A Phase 4 study testing Cangrelor in people with ST Segment Elevation Myocardial Infarction and Percutaneous Coronary Intervention, run by University of Florida at 1 site in United States.
Trial summary
In STEMI patients undergoing PPCI there is a delayed onset of action of oral P2Y12 receptor inhibitors, including prasugrel and ticagrelor. Crushing prasugrel and ticagrelor improves their PK and PD profiles as it favors drug absorption and onset of antiplatelet effects and because of this, it is commonly used in… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ST Segment Elevation Myocardial Infarction, Percutaneous Coronary Intervention
- What is being tested?
- Cangrelor
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Nov 2017to 13 Dec 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 with STEMI undergoing primary PPCI
- Age > 18 years old
Who cannot join
- Inability to provide written informed consent
- Known history of prior intracranial bleeding
- On treatment with a P2Y12 receptor antagonist (ticlopidine, clopidogrel, prasugrel, ticagrelor) in the prior 10 days
- Known allergies to aspirin, ticagrelor or cangrelor
- On treatment with oral anticoagulant
- Treatment with glycoprotein IIb/IIIa inhibitors
Show all 17Show fewer
- Fibrinolytics within 24 hours
- Active bleeding
- High risk of bleeding
- Known platelet count <80x106/mL
- Known hemoglobin <10 g/dL
- Intubated patients (prior to randomization)
- Known creatinine clearance <30 mL/minute or on hemodialysis.
- Known severe hepatic dysfunction
- Patients with sick sinus syndrome (SSS) or high degree AV block without pacemaker protection
- Current treatment with drugs interfering with CYP3A4 metabolism (to avoid interaction with ticagrelor): Ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and telithromizycin.
- Pregnant or lactating females.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Platelet Inhibition With CANgrelor and Crushed TICagrelor in STEMI Patients Undergoing Primary Percutaneous Coronary Intervention: The CANTIC Study
In STEMI patients undergoing PPCI there is a delayed onset of action of oral P2Y12 receptor inhibitors, including prasugrel and ticagrelor. Crushing prasugrel and ticagrelor improves their PK and PD profiles as it favors drug absorption and onset of antiplatelet effects and because of this, it is commonly used in STEMI patients undergoing PPCI. However, despite the use of crushed tablets, up to one-third of patients may still have high on-treatment platelet reactivity (HPR) within the first 2 hours after loading dose (LD) administration of these oral agents. Cangrelor is a potent intravenous P2Y12 receptor inhibitor with rapid onset and offset of action associated with a greater reduction in ischemic events compared with clopidogrel in P2Y12 receptor naïve patients undergoing PCI. To date most studies have explored cangrelor in the setting of PCI subjects treated with clopidogrel. The PD effects of cangrelor in STEMI patients undergoing PPCI treated with a newer generation P2Y12 receptor inhibitor and how this compares with a crushed formulation of the oral drug is unexplored. The aim of this prospective randomized study is to investigate the PD effects of cangrelor in STEMI patients undergoing PPCI treated with crushed ticagrelor.
Read the detailed description
In STEMI patients undergoing PPCI there is a delayed onset of action of oral P2Y12 receptor inhibitors, including prasugrel and ticagrelor, which require more than 2 hours to exert their full antiplatelet effects, and thus exposing these high-risk patients to an increased risk of early thrombotic complications. The mechanism of this delayed onset of antiplatelet effect is likely multifactorial due to the presence in the setting of STEMI of specific conditions that translate into delayed drug absorption which in turn affect the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of oral P2Y12 receptor inhibitors. Crushing prasugrel and ticagrelor improves their PK and PD profiles as it favors drug absorption and onset of antiplatelet effects and because of this, it is commonly used in STEMI patients undergoing PPCI. However, despite the use of crushed tablets, up to one-third of patients may still have high on-treatment platelet reactivity (HPR) within the first 2 hours after loading dose (LD) administration of these oral agents. Cangrelor is a potent intravenous P2Y12 receptor inhibitor with rapid onset and offset of action associated with a greater reduction in ischemic events compared with clopidogrel in P2Y12 receptor naïve patients undergoing PCI. To date most studies have explored cangrelor in the setting of PCI subjects treated with clopidogrel and the clinical profile of cangrelor among patients treated with prasugrel or ticagrelor is currently unknown. This is noteworthy because ACS patients, in particular STEMI undergoing PPCI, are commonly treated with either prasugrel or ticagrelor. PD investigations conducted in vitro or ex vivo in stable patients have shown cangrelor to be associated with enhanced platelet inhibition compared with that induced by prasugrel and ticagrelor. However, the PD effects of cangrelor in STEMI patients undergoing PPCI treated with a newer generation P2Y12 receptor inhibitor and how this compares with a crushed formulation of the oral drug is unexplored. The aim of this prospective randomized study is to investigate the PD effects of cangrelor in STEMI patients undergoing PPCI treated with crushed ticagrelor.
- Being tested
- Cangrelor, Placebo
- Keywords
- ticagrelor, cangrelor
- Medical subject headings
- ST Elevation Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CangrelorDrug
Also called Kangreal
Patients will be randomly assigned 1:1 to receive either cangrelor or matching placebo. The bolus will be administered at the same time of a 180 mg crushed ticagrelor loading dose and infusion will be continued for 2 h.
PlaceboOther
Patients will be randomly assigned 1:1 to receive either cangrelor or matching placebo. The bolus will be administered at the same time of a 180 mg crushed ticagrelor loading dose and infusion will be continued for 2 h.
| Study group | Role | What they receive |
|---|---|---|
| Cangrelor | Experimental | Cangrelor will be administered as 30 μg/kg bolus followed by 4 μg/kg/min infusion for 2 hours Receives: Drug: Cangrelor |
| Placebo | Placebo comparator | Normal saline bolus and infusion for 2 hours Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Platelet Reactivity Measured by VerifyNow PRU
Platelet reactivity at 30 minutes after starting cangrelor or placebo assessed by VerifyNow PRU and reported as P2Y12 Reaction Units (PRU)
Measured: 30 minutes
Secondary outcomes (1)
Platelet Reactivity Measured by Vasodilator-stimulated Phosphoprotein (VASP)
Platelet reactivity at 30 minutes after starting cangrelor or placebo measured by VASP and reported as platelet reactivity index (PRI%). Higher PRI% means higher platelet reactivity.
Measured: 30 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2017
- Study start20 Nov 2017
- Primary completion13 Dec 2018
- Study completion13 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for ST Segment Elevation Myocardial InfarctionStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- Chiesi Farmaceutici S.p.A.
- Responsible party
- Sponsor
- Investigators
- Dominick Angiolillo, MD, PhD, Principal investigator, University of Florida College of Medicine-Jacksonville
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03247738
- Sponsor's protocol ID
- IIS CHI001 WIRB
- Acronym
- CANTIC
- Status last verified
- Aug 2020
- First submitted
- 7 Aug 2017
- Last updated
- 9 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Luker J, Kuhr K, Sultan A, Nolker G, Omran H, Willems S, Andrie R, Schrickel JW, Winter S, Vollmann D, Tilz RR, Jobs A, Heeger CH, Metzner A, Meyer S, Mischke K, Napp A, Fahrig A, Steinhauser S, Brachmann J, Baldus S, Mahajan R, Sanders P, Steven D. Internal Versus External Electrical Cardioversion of Atrial Arrhythmia in Patients With Implantable Cardioverter-Defibrillator: A Randomized Clinical Trial. Circulation. 2019 Sep 24;140(13):1061-1069. doi: 10.1161/CIRCULATIONAHA.119.041320. Epub 2019 Aug 30.
PubMed 31466479Franchi F, Rollini F, Rivas A, Wali M, Briceno M, Agarwal M, Shaikh Z, Nawaz A, Silva G, Been L, Smairat R, Kaufman M, Pineda AM, Suryadevara S, Soffer D, Zenni MM, Bass TA, Angiolillo DJ. Platelet Inhibition With Cangrelor and Crushed Ticagrelor in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention. Circulation. 2019 Apr 2;139(14):1661-1670. doi: 10.1161/CIRCULATIONAHA.118.038317.
PubMed 30630341
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Platelet Inhibition With CANgrelor and Crushed TICagrelor in STEMI Patients Undergoing Primary Percutaneous Coronary Intervention: The CANTIC Study
- ClinicalTrials.gov ID
- NCT03247738
- Acronym / sponsor ID
- CANTIC / IIS CHI001 WIRB
- Keywords
- ticagrelor, cangrelor
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- Chiesi Farmaceutici S.p.A.
- Study start
- 20 Nov 2017 (actual)
- Primary completion
- 13 Dec 2018 (actual)
- Study completion
- 13 Dec 2018 (actual)
- First posted
- 14 Aug 2017 (actual)
- Results
- Posted 6 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In STEMI patients undergoing PPCI there is a delayed onset of action of oral P2Y12 receptor inhibitors, including prasugrel and ticagrelor. Crushing prasugrel and ticagrelor improves their PK and PD profiles as it favors drug absorption and onset of antiplatelet effects and because of this, it is commonly used in STEMI patients undergoing PPCI. However, despite the use of crushed tablets, up to one-third of patients may still have high on-treatment platelet reactivity (HPR) within the first 2 hours after loading dose (LD) administration of these oral agents. Cangrelor is a potent intravenous P2Y12 receptor inhibitor with rapid onset and offset of action associated with a greater reduction in ischemic events compared with clopidogrel in P2Y12 receptor naïve patients undergoing PCI. To date most studies have explored cangrelor in the setting of PCI subjects treated with clopidogrel. The PD effects of cangrelor in STEMI patients undergoing PPCI treated with a newer generation P2Y12 receptor inhibitor and how this compares with a crushed formulation of the oral drug is unexplored. The aim of this prospective randomized study is to investigate the PD effects of cangrelor in STEMI patients undergoing PPCI treated with crushed ticagrelor.
Detailed description
In STEMI patients undergoing PPCI there is a delayed onset of action of oral P2Y12 receptor inhibitors, including prasugrel and ticagrelor, which require more than 2 hours to exert their full antiplatelet effects, and thus exposing these high-risk patients to an increased risk of early thrombotic complications. The mechanism of this delayed onset of antiplatelet effect is likely multifactorial due to the presence in the setting of STEMI of specific conditions that translate into delayed drug absorption which in turn affect the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of oral P2Y12 receptor inhibitors. Crushing prasugrel and ticagrelor improves their PK and PD profiles as it favors drug absorption and onset of antiplatelet effects and because of this, it is commonly used in STEMI patients undergoing PPCI. However, despite the use of crushed tablets, up to one-third of patients may still have high on-treatment platelet reactivity (HPR) within the first 2 hours after loading dose (LD) administration of these oral agents. Cangrelor is a potent intravenous P2Y12 receptor inhibitor with rapid onset and offset of action associated with a greater reduction in ischemic events compared with clopidogrel in P2Y12 receptor naïve patients undergoing PCI. To date most studies have explored cangrelor in the setting of PCI subjects treated with clopidogrel and the clinical profile of cangrelor among patients treated with prasugrel or ticagrelor is currently unknown. This is noteworthy because ACS patients, in particular STEMI undergoing PPCI, are commonly treated with either prasugrel or ticagrelor. PD investigations conducted in vitro or ex vivo in stable patients have shown cangrelor to be associated with enhanced platelet inhibition compared with that induced by prasugrel and ticagrelor. However, the PD effects of cangrelor in STEMI patients undergoing PPCI treated with a newer generation P2Y12 receptor inhibitor and how this compares with a crushed formulation of the oral drug is unexplored. The aim of this prospective randomized study is to investigate the PD effects of cangrelor in STEMI patients undergoing PPCI treated with crushed ticagrelor.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cangrelor | Experimental | Drug: CangrelorCangrelor will be administered as 30 μg/kg bolus followed by 4 μg/kg/min infusion for 2 hours |
| Placebo | Placebo comparator | Other: PlaceboNormal saline bolus and infusion for 2 hours |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients with STEMI undergoing primary PPCI
- Age > 18 years old
Key exclusion criteria (17 listed)
- Inability to provide written informed consent
- Known history of prior intracranial bleeding
- On treatment with a P2Y12 receptor antagonist (ticlopidine, clopidogrel, prasugrel, ticagrelor) in the prior 10 days
- Known allergies to aspirin, ticagrelor or cangrelor
- On treatment with oral anticoagulant
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 |
|---|---|---|
| CangrelorAlso: KangrealPatients will be randomly assigned 1:1 to receive either cangrelor or matching placebo. The bolus will be administered at the same time of a 180 mg crushed ticagrelor loading dose and infusion will be continued for 2 h. | Drug | Cangrelor |
| PlaceboPatients will be randomly assigned 1:1 to receive either cangrelor or matching placebo. The bolus will be administered at the same time of a 180 mg crushed ticagrelor loading dose and infusion will be continued for 2 h. | Other | Placebo |
Primary outcome
Platelet Reactivity Measured by VerifyNow PRU
Time frame: 30 minutes
Platelet reactivity at 30 minutes after starting cangrelor or placebo assessed by VerifyNow PRU and reported as P2Y12 Reaction Units (PRU)
1 secondary outcome
Platelet Reactivity Measured by Vasodilator-stimulated Phosphoprotein (VASP)
Time frame: 30 minutes
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31466479Luker J, Kuhr K, Sultan A, Nolker G, Omran H, Willems S, Andrie R, Schrickel JW, Winter S, Vollmann D, Tilz RR, Jobs A, Heeger CH, Metzner A, Meyer S, Mischke K, Napp A, Fahrig A, Steinhauser S, Brachmann J, Baldus S, Mahajan R, Sanders P, Steven D. Internal Versus External Electrical Cardioversion of Atrial Arrhythmia in Patients With Implantable Cardioverter-Defibrillator: A Randomized Clinical Trial. Circulation. 2019 Sep 24;140(13):1061-1069. doi: 10.1161/CIRCULATIONAHA.119.041320. Epub 2019 Aug 30.
- Derived from this study: PubMed 30630341Franchi F, Rollini F, Rivas A, Wali M, Briceno M, Agarwal M, Shaikh Z, Nawaz A, Silva G, Been L, Smairat R, Kaufman M, Pineda AM, Suryadevara S, Soffer D, Zenni MM, Bass TA, Angiolillo DJ. Platelet Inhibition With Cangrelor and Crushed Ticagrelor in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention. Circulation. 2019 Apr 2;139(14):1661-1670. doi: 10.1161/CIRCULATIONAHA.118.038317.
- 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.
Dominick Angiolillo, MD, PhD principal investigator
University of Florida College of Medicine-Jacksonville
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Cangrelor in people with ST Segment Elevation Myocardial Infarction and Percutaneous Coronary Intervention, run by University of Florida at 1 site in United States.
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 2 inclusion and 17 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 9 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 6 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Platelet Reactivity Measured by VerifyNow PRU (time frame: 30 minutes). 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 NCT03247738, 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 9 Sep 2020.