Cangrelor in Comatose Survivors of OHCA Undergoing Primary PCI
Condition: Out-Of-Hospital Cardiac Arrest; Acute Coronary Syndrome
MeSH terms: Acute Coronary Syndrome; Heart Arrest; Out-of-Hospital Cardiac Arrest
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Cangrelor 50 MG
Intervention type(s): Drug
Intervention description(s): 30 mcg/kg bolus, then 4h infusion 4 mcg/kg/min
Other intervention name(s): Kengrexal 50 mg
Intervention MeSH terms: Cangrelor
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: cangrelor; P2Y12; out-of-hospital cardiac arrest; induced hypothermia; primary percutaneous coronary intervention