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

NCT ID: NCT02285751

Last Updated: 2019-08-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-11-30

Study Completion Date

2020-08-31

Brief Summary

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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.

Detailed Description

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Conditions

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Critical Illness

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

acetylsalicylic acid

Intervention Type DRUG

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.

Group Type EXPERIMENTAL

acetylsalicylic acid

Intervention Type DRUG

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

Group Type EXPERIMENTAL

acetylsalicylic acid

Intervention Type DRUG

75mg clopidogrel

control group for patients with high "on treatment" platelet reactivity to clopidogrel patients continue with standard treatment 75mg clopidogrel/day

Group Type ACTIVE_COMPARATOR

clopidogrel

Intervention Type DRUG

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

Group Type EXPERIMENTAL

prasugrel

Intervention Type DRUG

600mg clopidogrel

additional loading dose for 24 patients tested with high "on treatment" platelet reactivity to clopidogrel

Group Type EXPERIMENTAL

clopidogrel

Intervention Type DRUG

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

Group Type EXPERIMENTAL

ticagrelor

Intervention Type DRUG

prasugrel 10mg

patients treated with 10mg prasugrel daily

Group Type ACTIVE_COMPARATOR

prasugrel

Intervention Type DRUG

Interventions

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acetylsalicylic acid

Intervention Type DRUG

clopidogrel

Intervention Type DRUG

prasugrel

Intervention Type DRUG

ticagrelor

Intervention Type DRUG

Other Intervention Names

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100mg Thrombo-ASS 200mg Thrombo-ASS 81mg chewable aspirin 100mg intravenous acetylsalicylic acid 75mg po clopidogrel 600mg po clopidogrel (loading dose) 60mg prasugrel per os loading dose 10mg prasugrel per os daily 180mg ticagrelor per os (loading dose)

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Medical University of Vienna

OTHER

Sponsor Role lead

Responsible Party

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Bernd Jilma

Ao. Univ.-Prof. Dr. Bernd Jilma

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Bernd Jilma, Ao. Univ.-Prof. Dr. med

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna, Department of Clinical Pharmacology

Locations

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General Hospital

Vienna, , Austria

Site Status RECRUITING

Countries

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Austria

Central Contacts

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Bernd Jilma, Ao. Univ.-Prof. Dr. med.

Role: CONTACT

0043140400 ext. 2981

Facility Contacts

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Bernd Jilma, Ao. Univ.-Prof. Dr. med

Role: primary

0140400 ext. 2981

Other Identifiers

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2012-002226-76

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

HTPR-ICU

Identifier Type: -

Identifier Source: org_study_id

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