P3AMI Antiplatelet Trial
Condition: Heart Attack
MeSH terms: Myocardial Infarction
Study type: Interventional
Phase: Phase 4

Summary: 
      Major heart attacks are caused by a numerous factors, including sudden clot formation in a
      coronary artery leading to a blockage and heart muscle death. The clots are largely made of
      sticky clotting blood cells (platelets). A patient having a major heart attack is treated
      with emergency primary percutaneous coronary intervention (PPCI) where a wire and balloon are
      used to reopen the coronary artery and a stent (a slotted metal tube) is placed to keep the
      artery open.

      Aspirin, and one of two other antiplatelet drugs (prasugrel or ticagrelor) are given prior to
      PPCI to prevent further clots formation. Both antiplatelet drugs are taken in tablet form and
      in healthy stable patients these drugs take at least 30 min to 2 hours to exert an adequate
      effect. Often PPCI procedures are performed well within this timescale. It is possible that
      having a major heart attack limits the bodies ability to absorb the drugs also.

      In this study, patients with major or minor heart attacks will be given either prasugrel or
      ticagrelor as per licensed indications and guideline recommendations. A 15 ml blood sample
      will be taken at first balloon inflation to reopen the blocked artery, then after 20 minutes,
      60 minutes, and 4 hours after taking the drugs. Each blood sample will be subjected to a
      variety of tests to determine antiplatelet drug activity.

      This study will identify which of the two agents used are working effectively during PPCI,
      given the very short timescales involved. It will also show if patients with major heart
      attacks absorb the drugs less well than patients with less severe heart attacks. In the
      future it might be that an intravenous agent will be more valuable in the setting of PPCI.
    

Detailed description: 
      This is a pilot study by design, which will be nonrandomized in nature. A total of 90
      subjects will be included in the study distributed equally into 6 patient groups which have
      been carefully selected so that all patients will receive antiplatelet drugs as per current
      accepted NICE (National Institute for Health and aCare Excellence) guidelines and licensed
      indications.

      In the current ethically approved protocol ver 1.4 (5/11/12) Groups 1,3 and 4 have already
      been recruited to and a full data set has been collected; Group 1 STEMI (ST-segment elevation
      myocardial infarction) prasugrel Group 3 STEMI clopidogrel Group 4 NSTEMI (Non-ST segment
      elevation myocardial infarction) clopidogrel

      The current protocol allows for a specific group of NSTEMI patients (diabetic <75 years of
      age, >60 kg) treated with prasugrel to be recruited. The restrictive nature of these criteria
      would not allow us to make a direct comparison to STEMI patients treated with prasugrel. In
      light of this the eligibility criteria has been widened for NSTEMI patients to be treated
      with prasugrel. The proposed NSTEMI criteria is as follows:

        1. Group 2: Patients with NSTEMI who are under 75 years of age and greater than 60kg in
           weight receive prasugrel loading (60mg) (in line with the manufacturers recommendations
           and licensing) after the 4 hour sample collection period those patients who are treated
           with percutaneous coronary intervention will receive prasugrel at a maintenance dose of
           10mg daily (in line with NICE recommendations and local guidelines), those patients who
           do not proceed to be treated with percutaneous coronary intervention will be switched to
           clopidogrel 75mg daily (in line with NICE recommendations and local guidelines) on the
           following day.

           The investigators also propose to include recruitment of the following two groups in
           which ticagrelor will prescribed in accordance with NICE guidance and licenced
           indications:

        2. Group 5: Patients admitted with STEMI receiving ticagrelor loading (180 mg) and then
           maintenance (90mg bd per day)(in line with manufacturer's recommendations and
           licensing).

        3. Group 6: Patients Admitted with NSTEMI receiving ticagrelor loading (180 mg) and then
           maintenance (90mg bd per day)(in line with manufacturer's recommendations and licensing)
           The investigators will only begin recruitment to groups 5 and 6 once patient recruitment
           is completed in group 2

      PROCEDURE LOG:

      STEMI patients will be identified following admission for PPCI. Patient consent for this
      group shall be a 2 stage process. Initially, a shortened patient information sheet shall be
      read to the patient on admission prior to PPCI as to not delay treatment. Once verbal consent
      has been obtained a P2Y12 inhibitor ticagrelor will be administered to the patient as per
      current local and national guidance. The time of loading dose will be carefully recorded and
      the patient transferred to the cardiac catheterization suite for PPCI. After the insertion of
      the radial or femoral sheath, 15 ml (approx 3 teaspoonfuls in volume) of whole blood will be
      drawn from this sheath at 20 minutes post dosing (or as close to this time point as
      practicable) and also at the first balloon inflation time. A further 15 ml will be taken at
      60 minutes post dosing (or as close as is practicable). The second stage of consent will
      occur after PPCI when the patient has been transferred to the ward and is pain free and has
      been able to rest. At this stage a full patient information sheet shall be given to the
      patient to read and written consent will be sought. A final 15ml blood sample will be taken
      after 4 hours post dosing, after which the patient's participation in this study will come to
      an end.

      NSTEMI/UA (Unstable Angina) Potential patients will be approached by a member of the research
      team, who will offer the patient a full written patient information sheet and obtain written
      consent. Following consent the patient will have been administered a P2Y12 inhibitor
      (prasugrel or ticagrelor). The time of loading dose will be carefully recorded. 15 ml (approx
      3 teaspoonfuls in volume ) of blood will be taken at 20 minutes, 60 minutes and then 4 hours
      post dosing, after which the patient's participation in this study will come to an end.

      For both STEMI and NSTEMI/UA groups, aspirin will already have been given in the ambulance
      and will be assessed at 20 minutes after P2Y12 inhibitor loading and again at 60 minutes.

      Each blood sample taken will undergo a series of tests which will encompass the presence and
      function of the antiplatelet medication after a patient has suffered either a major or minor
      heart attack.
    

Intervention name(s): Prasugrel; Clopidogrel; ticagrelor
Intervention type(s): Drug; Drug; Drug
Intervention MeSH terms: Clopidogrel; Ticagrelor; Prasugrel Hydrochloride
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: STEMI; NSTEMI; PPCI