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P3AMI Antiplatelet Trial

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02376283
Recruitment Status : Completed
First Posted : March 3, 2015
Results First Posted : September 18, 2019
Last Update Posted : February 10, 2020
Sponsor:
Information provided by (Responsible Party):
The Royal Wolverhampton Hospitals NHS Trust

Tracking Information
First Submitted Date  ICMJE February 2, 2015
First Posted Date  ICMJE March 3, 2015
Results First Submitted Date  ICMJE June 25, 2019
Results First Posted Date  ICMJE September 18, 2019
Last Update Posted Date February 10, 2020
Actual Study Start Date  ICMJE March 9, 2015
Actual Primary Completion Date November 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 13, 2019)
  • Pharmacodynamic Assessment of Degree of Platelet Inhibition as Determined by Verify Now Point of Care Assay and Expressed as P2Y12 Reaction Units (PRU) [ Time Frame: Balloon Inflation as Baseline, 20, 60, 240 minutes ]
  • Pharmacokinetic Quantification of Plasma Concentration of Clopidogrel and Prasugrel Active Metabolite and Ticagrelor Parent Compound and Active Metabolite Assessed Using Liquid Chromatography in Tandem With Mass Spectrometry (LC-MS/MS) Expressed as ng/ml [ Time Frame: Balloon Inflation as Baseline, 20, 60, 240 minutes ]
    The parent compound of Ticagrelor was also analysed within the same patient group of Ticagrelor as it is a directly acting agent that does not require metabolic conversion to its active form.
Original Primary Outcome Measures  ICMJE
 (submitted: February 24, 2015)
  • The degree of platelet inhibition generated by the administration of prasugrel vs ticagrelor in STEMI patients as assessed by VerifyNow assay and VASP flow cytometry. [ Time Frame: 4 hours ]
  • To assess whether there is a difference in antiplatelet activity of prasugrel and ticagrelor in STEMI vs NSTEMI patients as assessed by VerifyNow assay and VASP flow cytometry. [ Time Frame: 4 hours ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 13, 2019)
Pharmacodynamic Assessment of Degree of Platelet Inhibition as Determined by VASP (Vasodilator Stimulated Phosphoprotein Phosphorylation) Flow Cytometry and Expressed as %PRI (Platelet Reactivity Index) [ Time Frame: Balloon Inflation as Baseline, 20, 60, 240 minutes ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 24, 2015)
  • Time course of plasma concentration of prasugrel and ticagrelor active metabolites in STEMI patients as assessed by liquid chromatography with tandem mass spectrometry. [ Time Frame: 4 hours ]
  • If there is a difference in plasma concentration of Ticagrelor and Prasugrel active metabolites in STEMI vs NSTEMI patients as assessed by liquid chromatography with tandem mass spectrometry. [ Time Frame: 4 hours ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE P3AMI Antiplatelet Trial
Official Title  ICMJE Pharmacokinetics and Pharmacodynamics of Platelet P2Y12 Inhibitors in Patients Undergoing Percutaneous Coronary Intervention (PCI) for Acute Myocardial Infarction: A Pilot Study
Brief 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Heart Attack
Intervention  ICMJE
  • Drug: Prasugrel
  • Drug: Clopidogrel
  • Drug: ticagrelor
Study Arms  ICMJE
  • STEMI prasugrel
    Patients with diabetes mellitus admitted with STEMI who are under 75 years of age and greater than 60Kg in weight receiving Prasugrel Loading (60mg) and maintenance (10mg per day).
    Intervention: Drug: Prasugrel
  • STEMI clopidogrel
    Patients admitted with STEMI over the age of 75 or under 60 Kg receiving clopidogrel loading (600 mg) and then maintenance (75mg per day).
    Intervention: Drug: Clopidogrel
  • NSTEMI clopidogrel
    Patients admitted with NSTEMI/UA over the age of 75 or under 60 Kg receiving clopidogrel loading (600 mg) and then maintenance (75mg per day).
    Intervention: Drug: Clopidogrel
  • Patients with NSTEMI
    who are under 75 years of age and greater than 60Kg in weight receiving Prasugrel loading (60mg) however: - i. After sample collection patients treated with intracoronary stent placement on the same day as loading will receive prasugrel maintenance dose (10mg per day) as per licensing agreement for prasugrel ii. After sample collection patients who are not stented after loading will receive clopidogrel maintenance dose (75mg per day).
    Interventions:
    • Drug: Prasugrel
    • Drug: Clopidogrel
  • Patients admitted with STEMI receiving ticagrelor loading
    Patients admitted with STEMI receiving ticagrelor loading (180 mg) and then maintenance (90mg bd per day)
    Intervention: Drug: ticagrelor
  • Patients Admitted with NSTEMI receiving ticagrelor loading
    Patients Admitted with NSTEMI receiving ticagrelor loading (180 mg) and then maintenance (90mg bd per day).
    Intervention: Drug: ticagrelor
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 13, 2019)
87
Original Estimated Enrollment  ICMJE
 (submitted: February 24, 2015)
90
Actual Study Completion Date  ICMJE November 2016
Actual Primary Completion Date November 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patients presenting with STEMI for PCI (characterized by chest discomfort, and prominent STsegment elevation)
  2. Patients presenting with NSTEMI (characterized by chest discomfort, raised levels of myocardial enzymes and/or STsegment depression or prominent T wave inversion)
  3. Able to give verbal consent (STEMI patients pre procedure) and/or written consent (STEMI after procedure and NSTEMI patients prior to enrolment).
  4. Age>18 years of age
  5. Able to take Aspirin and either prasugrel or ticagrelor.
  6. Have no concurrent septic or inflammatory illness
  7. Thienopyridine naive

Exclusion Criteria:

  1. Be unable to provide verbal and written consent
  2. Allergic to aspirin or any of the P2Y12 antagonists in the trial
  3. Have preexisting cardiogenic shock
  4. Have a concurrent septic or inflammatory disease e.g. rheumatoid arthritis, lupus, pneumonia.
  5. Already taking a P2Y12 inhibitor
  6. Known bleeding diathesis
  7. Patients under 75 years of age or under 60 kg or those who have had a previous stroke/transient ischaemic attack, will not be eligible for prasugrel but rather ticagrelor.
  8. Patients with a history of intracranial haemorrhage will not receive prasugrel or ticagrelor but rather will receive treatment with clopidogrel.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02376283
Other Study ID Numbers  ICMJE 2012-004-04-02-CARD
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party The Royal Wolverhampton Hospitals NHS Trust
Study Sponsor  ICMJE The Royal Wolverhampton Hospitals NHS Trust
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: James Cotton, MD, FRCP The Royal Wolverhampton NHS Trust
PRS Account The Royal Wolverhampton Hospitals NHS Trust
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP