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Trial record 66 of 508 for:    ASPIRIN AND P2

High "on Treatment" Platelet Reactivity in the Intensive Care Unit

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ClinicalTrials.gov Identifier: NCT02285751
Recruitment Status : Recruiting
First Posted : November 7, 2014
Last Update Posted : August 20, 2019
Sponsor:
Information provided by (Responsible Party):
Bernd Jilma, Medical University of Vienna

Brief Summary:

High "on treatment" platelet reactivity is defined as a poor pharmacodynamic response to the administration of acetylsalicylic acid or clopidogrel. acetylsalicylic acid and clopidogrel are drugs commonly used to reduce platelet activity and prevent cardiovascular events. High "on treatment" platelet reactivity is associated with a higher cardiovascular event rate.

Ticagrelor and prasugrel, like clopidogrel both P2Y12 inhibitors are effective in treating patients with High "on treatment" platelet reactivity to clopidogrel.

Critically ill patients are a unique population with altered pharmacokinetic and pharmacodynamic properties. Gastrointestinal dysmotility with associated altered resorption and impaired microvascular function occur frequently in critically ill patients and may lead to altered resorption of orally administered drugs.

The investigators will test a minimum of 100 patients treated with 100mg acetylsalicylic acid per os and 100 patients treated with 75mg clopidogrel per os to calculate the prevalence of high "on treatment" platelet reactivity.

30 patients with high "on treatment" platelet reactivity to acetylsalicylic acid will be randomized to three new treatment groups. In the first group patients will receive 200mg acetylsalicylic acid per os, in the second group 100mg acetylsalicylic acid intravenously and in the third group 81mg chewable acetylsalicylic acid. Each group will contain 10 patients. Pharmacokinetics and pharmacodynamics will be reassessed to evaluate the new treatment.

36 patients with high "on treatment" platelet reactivity to clopidogrel will be randomized to receive either an additional loading dose of 600mg clopidogrel (n=24) or to continue normal treatment as a control group (n=12). Pharmacokinetics and pharmacodynamics will be reassessed and those patients, who are tested again to have high "on treatment" platelet reactivity in spite of the additional loading dose, will now be randomized to receive either ticagrelor or prasugrel. The investigators expect about six patients per group. The twelve patients in the control group will continue normal treatment (75mg/day) until the end of the study. Pharmacokinetics and pharmacodynamics of ticagrelor and prasugrel will be assessed. Any patient, who is tested again with high "on treatment" platelet reactivity in spite of receiving prasugrel or ticagrelor, will be finally switched to the opposite drug and a final high "on treatment" platelet reactivity testing will be conducted.

16 patients who are treated with 10mg prasugrel per os will be tested for HTPR and if positively tested will be switched to 2x90mg ticagrelor per os per day. Platelet reactivity will be reassessed to test whether switching the medication benefits the patients.


Condition or disease Intervention/treatment Phase
Critical Illness Drug: acetylsalicylic acid Drug: clopidogrel Drug: prasugrel Drug: ticagrelor Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: High "on Treatment" Platelet Reactivity in the Intensive Care Unit
Study Start Date : November 2012
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : August 2020

Arm Intervention/treatment
Experimental: 200mg acetylsalicylic acid per os
patients with high "on treatment" platelet reactivity to acetylsalicylic acid are randomized to 3 different groups, one group receives 200mg acetylsalicylic acid per os
Drug: acetylsalicylic acid
Other Names:
  • 100mg Thrombo-ASS
  • 200mg Thrombo-ASS
  • 81mg chewable aspirin
  • 100mg intravenous acetylsalicylic acid

Experimental: 100mg acetylsalicylic acid intravenous
patients with high "on treatment" platelet reactivity to acetylsalicylic acid are randomized to 3 different groups, one group receives 100mg acetylsalicylic acid intravenously.
Drug: acetylsalicylic acid
Other Names:
  • 100mg Thrombo-ASS
  • 200mg Thrombo-ASS
  • 81mg chewable aspirin
  • 100mg intravenous acetylsalicylic acid

Experimental: 81 mg chewable acetylsalicylic acid
patients with high "on treatment" platelet reactivity to acetylsalicylic acid are randomized to 3 different groups, one group receives 81mg chewable acetylsalicylic acid
Drug: acetylsalicylic acid
Other Names:
  • 100mg Thrombo-ASS
  • 200mg Thrombo-ASS
  • 81mg chewable aspirin
  • 100mg intravenous acetylsalicylic acid

Active Comparator: 75mg clopidogrel
control group for patients with high "on treatment" platelet reactivity to clopidogrel patients continue with standard treatment 75mg clopidogrel/day
Drug: clopidogrel
Other Names:
  • 75mg po clopidogrel
  • 600mg po clopidogrel (loading dose)

Experimental: 60mg prasugrel
Loading dose of prasugrel for patients who remain tested with high "on treatment" platelet reactivity in spite of having received an additional loading dose of 600mg clopidogrel
Drug: prasugrel
Other Names:
  • 60mg prasugrel per os loading dose
  • 10mg prasugrel per os daily

Experimental: 600mg clopidogrel
additional loading dose for 24 patients tested with high "on treatment" platelet reactivity to clopidogrel
Drug: clopidogrel
Other Names:
  • 75mg po clopidogrel
  • 600mg po clopidogrel (loading dose)

Experimental: 180mg ticagrelor
Loading dose of ticagrelor for patients who remain tested with high "on treatment" platelet reactivity in spite of having received an additional loading dose of 600mg clopidogrel Loading dose of ticagrelor for patients who remain tested with high "on treatment" platelet reactivity after being treated with 10mg prasugrel daily
Drug: ticagrelor
Other Name: 180mg ticagrelor per os (loading dose)

Active Comparator: prasugrel 10mg
patients treated with 10mg prasugrel daily
Drug: prasugrel
Other Names:
  • 60mg prasugrel per os loading dose
  • 10mg prasugrel per os daily




Primary Outcome Measures :
  1. pharmacodynamics (Arachidonic acid induced aggregation test with multiplate electrode aggregometry) [ Time Frame: on average 3 days ]

    Arachidonic acid induced aggregation test with multiplate electrode aggregometry of patients with high "on treatment" platelet reactivity to acetylsalicylic acid after receiving new treatments as explained.

    adenosine diphosphate induced aggregation tested with multiplate electrode aggregometry of patients with high "on treatment" platelet reactivity to clopidogrel after an additional loading dose clopidogrel, or after receiving prasugrel or ticagrelor



Secondary Outcome Measures :
  1. Prevalence of high "on-treatment" platelet reactivity in the intensive care unit [ Time Frame: maximum 2 weeks after admission ]
    percentage of patients tested with high "on treatment" platelet reactivity according to defined values

  2. Evaluation of pharmacokinetics (Serum levels of Salicylate/acetylsalicylic acid, clopidogrel-active metabolite, prasugrel-active metabolite, ticagrelor active-metabolite) [ Time Frame: on average 3 days ]
    Serum levels of Salicylate/acetylsalicylic acid, clopidogrel-active metabolite, prasugrel-active metabolite, ticagrelor active-metabolite

  3. intensive care unit mortality [ Time Frame: maximum 90 days ]
    discharge of ICU

  4. comparison of hemodynamically stable vs unstable ((defined by serum lactate>2.1mmol/l, need for circulatory support) [ Time Frame: maximum 3 days ]
    hemodynamically stable vs unstable (defined by serum lactate>2.1mmol/l, need for circulatory support)

  5. major bleeding (defined by TIMI-TRITON-38 criteria) [ Time Frame: average of 2 weeks within inclusion ]
    assessment of major bleeding incidences defined by TIMI-TRITON-38 criteria



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • >18years of age
  • admittance to an intensive care unit

Exclusion Criteria:

  • recent surgery
  • active bleeding
  • known coagulation disorders
  • discretion of the physician
  • terminal illness (anticipated life expectancy < 3months; e.g. due to cancer)
  • pregnancy
  • <20000 platelets

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02285751


Contacts
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Contact: Bernd Jilma, Ao. Univ.-Prof. Dr. med. 0043140400 ext 2981 bernd.jilma@meduniwien.ac.at

Locations
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Austria
General Hospital Recruiting
Vienna, Austria, 1090
Contact: Bernd Jilma, Ao. Univ.-Prof. Dr. med    0140400 ext 2981    bernd.jilma@meduniwien.ac.at   
Sponsors and Collaborators
Medical University of Vienna
Investigators
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Principal Investigator: Bernd Jilma, Ao. Univ.-Prof. Dr. med Medical University of Vienna, Department of Clinical Pharmacology

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Responsible Party: Bernd Jilma, Ao. Univ.-Prof. Dr. Bernd Jilma, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT02285751     History of Changes
Other Study ID Numbers: HTPR-ICU
2012-002226-76 ( EudraCT Number )
First Posted: November 7, 2014    Key Record Dates
Last Update Posted: August 20, 2019
Last Verified: August 2019
Keywords provided by Bernd Jilma, Medical University of Vienna:
high on treatment platelet reactivity
acetylsalicylic acid
clopidogrel
prasugrel
ticagrelor
critically ill
pharmacokinetic
pharmacodynamics
Additional relevant MeSH terms:
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Aspirin
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Critical Illness
Disease Attributes
Pathologic Processes
Clopidogrel
Ticagrelor
Prasugrel Hydrochloride
Platelet Aggregation Inhibitors
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics