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

NCT02285751 | Unknown Phase 2 DMC

• 2 other identifiers: HTPR-ICU2012-002226-76
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

Critical Illness

Keywords

high on treatment platelet reactivity; acetylsalicylic acid; clopidogrel; prasugrel; ticagrelor; critically ill; pharmacokinetic; pharmacodynamics

Outcome Measures

Primary Outcomes (1)

• pharmacodynamics (Arachidonic acid induced aggregation test with multiplate electrode aggregometry)

  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

  on average 3 days

Secondary Outcomes (5)

• Prevalence of high "on-treatment" platelet reactivity in the intensive care unit

  maximum 2 weeks after admission

• Evaluation of pharmacokinetics (Serum levels of Salicylate/acetylsalicylic acid, clopidogrel-active metabolite, prasugrel-active metabolite, ticagrelor active-metabolite)

  on average 3 days

• intensive care unit mortality

  maximum 90 days

• comparison of hemodynamically stable vs unstable ((defined by serum lactate>2.1mmol/l, need for circulatory support)

  maximum 3 days

• major bleeding (defined by TIMI-TRITON-38 criteria)

  average of 2 weeks within inclusion

Study Arms (8)

200mg acetylsalicylic acid per os

EXPERIMENTAL

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

100mg acetylsalicylic acid intravenous

EXPERIMENTAL

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

81 mg chewable acetylsalicylic acid

EXPERIMENTAL

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

75mg clopidogrel

ACTIVE COMPARATOR

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

Drug: clopidogrel

60mg prasugrel

EXPERIMENTAL

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

600mg clopidogrel

EXPERIMENTAL

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

Drug: clopidogrel

180mg ticagrelor

EXPERIMENTAL

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

prasugrel 10mg

ACTIVE COMPARATOR

patients treated with 10mg prasugrel daily

Drug: prasugrel

Interventions

acetylsalicylic acid DRUG

Also known as: 100mg Thrombo-ASS, 200mg Thrombo-ASS, 81mg chewable aspirin, 100mg intravenous acetylsalicylic acid

100mg acetylsalicylic acid intravenous; 200mg acetylsalicylic acid per os; 81 mg chewable acetylsalicylic acid

clopidogrel DRUG

Also known as: 75mg po clopidogrel, 600mg po clopidogrel (loading dose)

600mg clopidogrel; 75mg clopidogrel

prasugrel DRUG

Also known as: 60mg prasugrel per os loading dose, 10mg prasugrel per os daily

60mg prasugrel; prasugrel 10mg

ticagrelor DRUG

Also known as: 180mg ticagrelor per os (loading dose)

180mg ticagrelor

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

General Hospital

Vienna, 1090, Austria

RECRUITING

MeSH Terms

Conditions

Critical Illness

Interventions

Aspirin; Clopidogrel; Prasugrel Hydrochloride; Ticagrelor

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Piperazines; Adenosine; Purine Nucleosides; Purines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

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

  Medical University of Vienna, Department of Clinical Pharmacology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

CONTACT

0043140400; bernd.jilma@meduniwien.ac.at

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ao. Univ.-Prof. Dr. Bernd Jilma

Study Record Dates

• First Submitted: October 24, 2012
• First Posted: November 7, 2014
• Study Start: November 1, 2012
• Primary Completion: July 1, 2020
• Study Completion: August 1, 2020
• Last Updated: August 20, 2019

Record last verified: 2019-08

Locations

AU (1)