Condition or disease | Intervention/treatment | Phase |
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Out-Of-Hospital Cardiac Arrest Acute Coronary Syndrome | Drug: Cangrelor 50 MG | Phase 4 |
Coronary artery disease is an important cause of out-of hospital cardiac arrest (OHCA) and around 80 % of patients after OHCA are comatose. Considering patient's history, details concerning OHCA and ECG changes the decision on urgent cardiac catheterization is made. In case of significant coronary artery stenosis/occlusion on primary percutaneous coronary intervention stent implantation is usually needed. Dual antiplatelet therapy is the cornerstone of stent thrombosis prevention. Patients who are comatose after the return of spontaneous circulation (ROSC) differ from conscious survivors of OHCA because they are not able to take antiplatelet drugs, such as P2Y12 inhibitors, orally. Due to the need for nasogastric/ orogastric tube insertion there is a significant delay until optimal antiplatelet effect is achieved. Furthermore, there are other factors that have an impact on the pharmacokinetics of P2Y12 inhibitors, such as therapeutic hypothermia, gastroparesis, gastrointestinal tract hypoperfusion and platelet hyperreactivity because of systemic inflammatory response syndrome. These characteristics make acute and subacute stent thrombosis more common in comatose OHCA survivors leading to increased morbidity and mortality.
Heparin is the primary anticoagulant drug for comatose patients after OHCA. Antiplatelet therapy consists of intravenous aspirin and P2Y12 inhibitor. Ticagrelor is the most potent of the latter. It is available only as a tablet, which has to be crushed and dissolved and then given via nasogastric or orogastric tube. A recent study by Steblovnik et al. has shown there is an approximately 4-hour gap of inadequate platelet inhibition in comatose OHCA even if the most potent P2Y12 inhibitor ticagrelor is used. Prueller made a retrospective study assessing the addition of intravenous P2Y12 inhibitor cangrelor as a bridge of this gap to standard care. The results showed there is a significant antiplatelet effect when using cangrelor with no added bleeding risk. After literature review no prospective randomised study has been done comparing cangrelor-bridge to standard care with dual antiplatelet therapy (aspirin and ticagrelor).
The investigator's study is a single-blinded, prospective randomised study taking place at University Medical Centre Ljubljana. Thirty comatose survivors of OHCA will be randomised at the start of primary PCI into a test and control group. The control group will receive standard care with intravenous aspirin and dissolved ticagrelor tablets given via enteral tube. The test group patients will receive an additional P2Y12 bridging therapy: a bolus of cangrelor at the start of the PCI (30 mcg/kg) followed by a continuous 4-hour infusion (4 mcg/kg/min). Heparin will be used as per guidelines for a target ACT of 250-300 seconds at the time of PCI. Interventional cardiologist will decide on the use of eptifibatide (GP IIb/IIIa antagonist). Therapeutic hypothermia will be started in the catheterisation laboratory. All patients will be transferred to ICU after the procedure and level of platelet inhibition will be tested 1, 3 and 5 hours after the start of cangrelor infusion with VerifyNow and Multiplate systems. In the control group blood will be drawn at the same time intervals. Further management of patients in both arms will be no different from regular care.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 30 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Single (Participant) |
Primary Purpose: | Treatment |
Official Title: | Platelet Inhibition With Cangrelor in Comatose Survivors of Out-of-hospital Cardiac Arrest Undergoing Primary Percutaneous Coronary Intervention |
Actual Study Start Date : | July 1, 2019 |
Estimated Primary Completion Date : | December 2022 |
Estimated Study Completion Date : | December 2023 |
Arm | Intervention/treatment |
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Experimental: Cangrelor + Ticagrelor
Bolus of cangrelor (30 mcg/kg) and immediately afterwards a continuous intravenous infusion of 4 mcg/kg/min at the start of the primary percutaneous coronary intervention. Crushed and dissolved ticagrelor tablets (180 mg) will be given via inserted enteral tube.
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Drug: Cangrelor 50 MG
30 mcg/kg bolus, then 4h infusion 4 mcg/kg/min
Other Name: Kengrexal 50 mg
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No Intervention: Ticagrelor
Crushed and dissolved ticagrelor tablets (180 mg) will be given via enteral tube (standard care).
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Standardized bleeding definition as described by Bleeding Academic Research Consortium (BARC).
Type 0: no bleeding.
Significant bleeding will be defined as BARC 2, 3 and 5 or the need for discontinuation of cangrelor infusion.
Final angiographic result as evaluated by independent blinded interventional cardiologist. Defined as thrombolysis in myocardial infarction (TIMI) flow at the end of the procedure.
TIMI 0 flow - absence of any antegrade flow beyond a coronary occlusion TIMI 1 flow - faint antegrade coronary flow beyond the occlusion, with incomplete filling of the distal coronary bed TIMI 2 flow - delayed or sluggish antegrade flow with complete filling of the distal territory TIMI 3 flow - normal flow filling the distal coronary bed completely
Residual thrombus or peripheral embolization will also be noted.
Probable or definitive stent thrombosis according to Academic Research Consortium classification (ARC) of stent thrombosis.
Definite stent thrombosis - confirmed at angiography or autopsy. Probable stent thrombosis - unexplained death within 30 days after P-PCI or new myocardial infarction in P-PCI vessel territory.
Probable or definitive stent thrombosis according to Academic Research Consortium classification (ARC) of stent thrombosis based on timing of events.
Acute stent thrombosis 0-24 hours after stent implantation Subacute stent thrombosis 24 hours to 30 days after stent implantation
Survival to discharge from hospital defined as Cerebral performance category (CPC).
CPC 1 - good cerebral performance (normal life). Conscious, alert, able to work and lead a normal life.
CPC 2 - moderate cerebral disability (disabled but independent) CPC 3 - severe cerebral disability (conscious but disabled and dependent) CPC 4 - coma or vegetative state (unconscious) CPC 5 - brain death
Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Marko Noc, MD PhD | 0038615222296 | marko.noc@mf.uni-lj.si | |
Contact: Peter Kordis, MD | pkordis@gmail.com |
Slovenia | |
University Medical Centre Ljubljana | Recruiting |
Ljubljana, Slovenia, 1000 | |
Contact: Marko Noc, MD PhD 0038615222296 marko.noc@mf.uni-lj.si | |
Contact: Peter Kordis, MD pkordis@gmail.com |
Principal Investigator: | Marko Noc, MD PhD | University Medical Centre Ljubljana |
Tracking Information | |||||||||
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First Submitted Date ICMJE | April 1, 2019 | ||||||||
First Posted Date ICMJE | July 2, 2019 | ||||||||
Last Update Posted Date | February 17, 2021 | ||||||||
Actual Study Start Date ICMJE | July 1, 2019 | ||||||||
Estimated Primary Completion Date | December 2022 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Same as current | ||||||||
Change History | |||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | Cangrelor in Comatose Survivors of OHCA Undergoing Primary PCI | ||||||||
Official Title ICMJE | Platelet Inhibition With Cangrelor in Comatose Survivors of Out-of-hospital Cardiac Arrest Undergoing Primary Percutaneous Coronary Intervention | ||||||||
Brief Summary | The main objective of the trial is to find out if 4-hour continuous infusion of parenteral P2Y12 inhibitor cangrelor at the start of primary percutaneous coronary intervention (PCI) immediately and effectively suppresses platelet activity in comatose survivors of out-of-hospital cardiac arrest (OHCA). Half of the participants will receive the standard care of dual antiplatelet therapy - acetysalicylic acid and ticagrelor tablets via nasogastric or orogastric tube and the other half the standard care with additional cangrelor infusion at the start of the PCI. | ||||||||
Detailed Description |
Coronary artery disease is an important cause of out-of hospital cardiac arrest (OHCA) and around 80 % of patients after OHCA are comatose. Considering patient's history, details concerning OHCA and ECG changes the decision on urgent cardiac catheterization is made. In case of significant coronary artery stenosis/occlusion on primary percutaneous coronary intervention stent implantation is usually needed. Dual antiplatelet therapy is the cornerstone of stent thrombosis prevention. Patients who are comatose after the return of spontaneous circulation (ROSC) differ from conscious survivors of OHCA because they are not able to take antiplatelet drugs, such as P2Y12 inhibitors, orally. Due to the need for nasogastric/ orogastric tube insertion there is a significant delay until optimal antiplatelet effect is achieved. Furthermore, there are other factors that have an impact on the pharmacokinetics of P2Y12 inhibitors, such as therapeutic hypothermia, gastroparesis, gastrointestinal tract hypoperfusion and platelet hyperreactivity because of systemic inflammatory response syndrome. These characteristics make acute and subacute stent thrombosis more common in comatose OHCA survivors leading to increased morbidity and mortality. Heparin is the primary anticoagulant drug for comatose patients after OHCA. Antiplatelet therapy consists of intravenous aspirin and P2Y12 inhibitor. Ticagrelor is the most potent of the latter. It is available only as a tablet, which has to be crushed and dissolved and then given via nasogastric or orogastric tube. A recent study by Steblovnik et al. has shown there is an approximately 4-hour gap of inadequate platelet inhibition in comatose OHCA even if the most potent P2Y12 inhibitor ticagrelor is used. Prueller made a retrospective study assessing the addition of intravenous P2Y12 inhibitor cangrelor as a bridge of this gap to standard care. The results showed there is a significant antiplatelet effect when using cangrelor with no added bleeding risk. After literature review no prospective randomised study has been done comparing cangrelor-bridge to standard care with dual antiplatelet therapy (aspirin and ticagrelor). The investigator's study is a single-blinded, prospective randomised study taking place at University Medical Centre Ljubljana. Thirty comatose survivors of OHCA will be randomised at the start of primary PCI into a test and control group. The control group will receive standard care with intravenous aspirin and dissolved ticagrelor tablets given via enteral tube. The test group patients will receive an additional P2Y12 bridging therapy: a bolus of cangrelor at the start of the PCI (30 mcg/kg) followed by a continuous 4-hour infusion (4 mcg/kg/min). Heparin will be used as per guidelines for a target ACT of 250-300 seconds at the time of PCI. Interventional cardiologist will decide on the use of eptifibatide (GP IIb/IIIa antagonist). Therapeutic hypothermia will be started in the catheterisation laboratory. All patients will be transferred to ICU after the procedure and level of platelet inhibition will be tested 1, 3 and 5 hours after the start of cangrelor infusion with VerifyNow and Multiplate systems. In the control group blood will be drawn at the same time intervals. Further management of patients in both arms will be no different from regular care. |
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Study Type ICMJE | Interventional | ||||||||
Study Phase ICMJE | Phase 4 | ||||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single (Participant) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE | Drug: Cangrelor 50 MG
30 mcg/kg bolus, then 4h infusion 4 mcg/kg/min
Other Name: Kengrexal 50 mg
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Study Arms ICMJE |
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Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE |
30 | ||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||
Estimated Study Completion Date ICMJE | December 2023 | ||||||||
Estimated Primary Completion Date | December 2022 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 70 Years (Adult, Older Adult) | ||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | Slovenia | ||||||||
Removed Location Countries | |||||||||
Administrative Information | |||||||||
NCT Number ICMJE | NCT04005729 | ||||||||
Other Study ID Numbers ICMJE | KOIIM-2019-1 | ||||||||
Has Data Monitoring Committee | Not Provided | ||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | Marko Noc, University Medical Centre Ljubljana | ||||||||
Study Sponsor ICMJE | University Medical Centre Ljubljana | ||||||||
Collaborators ICMJE | Chiesi Slovenija, d.o.o. | ||||||||
Investigators ICMJE |
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PRS Account | University Medical Centre Ljubljana | ||||||||
Verification Date | February 2021 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |