Cangrelor in Comatose Survivors of OHCA Undergoing Primary PCI

NCT ID: NCT04005729

Last Updated: 2021-12-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-01
• Study Completion Date: 2021-11-27

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.

Conditions

Out-Of-Hospital Cardiac Arrest; Acute Coronary Syndrome

Keywords

cangrelor; P2Y12; out-of-hospital cardiac arrest; induced hypothermia; primary percutaneous coronary intervention

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Cangrelor 50 MG

Intervention Type: DRUG

30 mcg/kg bolus, then 4h infusion 4 mcg/kg/min

Ticagrelor

Crushed and dissolved ticagrelor tablets (180 mg) will be given via enteral tube (standard care).

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Cangrelor 50 MG

30 mcg/kg bolus, then 4h infusion 4 mcg/kg/min

Intervention Type: DRUG

Other Intervention Names

Kengrexal 50 mg

Eligibility Criteria

Inclusion Criteria

• age 18 to 70 years
• comatose survivors of out-of-hospital cardiac arrest undergoing primary percutaneous coronary intervention
• treatment with induced therapeutic hypothermia
• no contraindication for dual antiplatelet therapy

Exclusion Criteria

• pregnancy
• patients without return of spontaneous circulation or patients on ECMO
• history of recent P2Y12 use (last 7 days)
• history of recent vitamin K antagonist or NOAC use (last 14 days)
• active bleeding
• history of transient ischemic attack or cerebral vascular insult
• strong bleeding tendency (Child C liver cirrhosis, stage IV-V chronic renal disease)
• history of allergic reactions to acetylsalicylic acid, heparin or P2Y12 inhibitors
• terminal disease or life expectancy less than 1 year

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chiesi Slovenija, d.o.o.

INDUSTRY

Sponsor Role: collaborator

University Medical Centre Ljubljana

OTHER

Sponsor Role: lead

Responsible Party

Marko Noc

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marko Noc, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Centre Ljubljana

Locations

University Medical Centre Ljubljana

Ljubljana, , Slovenia

Countries

Slovenia

References

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Reference Type: BACKGROUND

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Other Identifiers

KOIIM-2019-1

Identifier Type: -

Identifier Source: org_study_id