Ticagrelor for the Comatose
Condition: Comatose
MeSH terms: Coma
Study type: Observational

Summary: 
      The study will investigate the effect of the oral antiplatelet agent ticagrelor (Brilique)
      when it is administrated through a nasogastric tube in comatose patients. The platelet
      function can be determined by various platelet function tests (PFT), Multiplate and VerifyNow
      . As control, the reference intervals from the literature are used. Futhermore, plasma
      concentrations of the active metabolite will be determined at aeveral timepoints after first
      intake of a bolus dose.
    

Detailed description: 
      Study population:

      Fifty patients admitted after cardiac arrest and who have all undergone acutte PCI will be
      inclded in the trial.

      All patients hospitalized at the cardiologic intensive department, RH, who are receiving
      ticagrelor (Brilique) through a nasogastric tube can be enrolled in the study. Administration
      of ticagrelor will follow usual indications and will thus only be used for patients
      considered to suffer from acute coronary syndromes (ACS). Blood samples are collected from an
      already inserted central venous catheter (CVC) and will therefore not affect the patients any
      further. The first samples will be collected directly before the first doses of medicine is
      given (t0), the samples are thereafter being repeatedly taken after (2(±1), 4(±1),
      8(±1),12(±1), and 24(±2) hours, hereafter daily (kl. 6-8 am) until after the first day where
      the patient can receive tablets orally, or until intensive care treatment is terminated
      (though, at most 5 days of sampling, addition to the first day).

      Medical treatment

      All study participants will be receiving antithrombotic treatment on clinical indication:
      aspirin + ticagrelor (brilique), thus no antithrombotic is given without indication and doses
      (bolus and maintain dose) is given according to the product information. Time sets for
      medicine administration is controlled by the EPM (electronic patient medication module). The
      Ticagrelor used is "medicine-off-the-shelf" administrated in following doses:

      Ticagrelor: bolus 180 mg p.o. as soon as possible after PCI and after insertion of a
      naso-gastic tube. Maintenance doses (90 mg) are administrated at 6 AM (+/- 1h) and 6PM (+/-
      1h) with the first maintenance dose administrated < 12 hours after bolus a 6AM or 6 PM
      whatever comes first. Contraindications as stated in the respectively product's summary are
      followed.

      Blood samples Blood collected for platelet function analysis are analysed immediately by
      VerifyNow and Multiplate and TEG-platelet mapping if available. In addition, 50 ml of blood
      is saved in a research bio bank for a collected analysis of concentrations of ticagrelor
      (active metabolite and parent compound) at the end of study. Residual blood will be
      destroyed. The maximum total amount of blood collected will be 150 ml.

      Informed consent in a trial of in-capacitated patients In the trial, patients who all are
      unconscious due to prior cardiac arrest or due to cardiogenic shock are participating. Most
      of the patients will be connected to life support and others are in unconscious states, which
      exclude the possibility of obtaining an informed agreement. All patients are > 18 years old.

      The study will be conducted under Danish and international guidelines for good clinical
      practice (ICHP-GCP) and the study are approved by the regional scientific ethical committee
      and the Danish Medical Agency. The participating study persons will all be unconscious,
      sedated or in a cerebral situation where you cannot reasonable consider involvement in a
      scientific study, and they are therefore not able to give informed consent in the acute
      phase. Current guidelines recommend acute revascularization and if necessary, circulation
      support and/or a cooling regimen and all treatment will be in accordance with local practice
      Inclusion in the project before obtaining informed consent can be justified according to the
      committee law's § 12. There are established a committee of two "legal guardians" (Danish:
      forsøgsværge), who have to agree to the patient's involvement in the trial and will make an
      individual judgement of the single patient's suitability to participate. The "legal guardian"
      (Danish: forsøgsværge) will at the time, receive the updated study protocol and all the
      information material which otherwise would have been presented to the patient/next of kin in
      the context of obtaining informed consent.

      Study procedures can start after accept from the legal guardian (Danish:forsøgsværge) however
      subsequent informed consent from the patient's next-of-kin should be obtained as soon as
      possible, as well as from the patient's general practitioner/health officer.

      Patients who regain their conscious will be asked for informed agreement. The agreeing part
      will be provided with information in word and speech regarding the study, so as the concerned
      will be able to make an informed decision about participation in the trial. The concerned
      part will be informed by the, for the study responsible, doctor or the attending doctor, who
      will be trained in the protocol. The declaration of consent has to be signed by the patient
      himself or his/her next-of-kin, as well as by the investigator who obtains the informed
      agreement.
    

Observational model: Case-Only
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        The study population consists of 50 unconscious patients, primary due to cardiac arrest or
        cardiogenic shock. All patients have been undergoing recent percutaneous coronary
        intervention (PCI) and are hospitalized at the cardiac intensive care unit.
      
Biospecimen description: 
      plasma and urine
    
Keywords: ticagrelor; platelet function test; comatose; PCI; naso-gastric tube