Critical IllnessPhase 2NCT02285751
High "on Treatment" Platelet Reactivity in the Intensive Care Unit
A Phase 2 study testing acetylsalicylic acid, clopidogrel and prasugrel in people with Critical Illness, run by Medical University of Vienna at 1 site in Austria.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Critical Illness
- What is being tested?
- acetylsalicylic acid, clopidogrel and prasugrel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteAustria
- Study dates
- Nov 2012to Aug 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- >18years of age
- admittance to an intensive care unit
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Austria1 site, 1 recruiting
- Recruiting
General Hospital
Vienna, 1090
Bernd Jilma, Ao. Univ.-Prof. Dr. med, 0140400 ext. 2981, bernd.jilma@meduniwien.ac.at
About this study
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.
Read more
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
- Being tested
- acetylsalicylic acid, clopidogrel, prasugrel, ticagrelor
- Keywords
- high on treatment platelet reactivity, acetylsalicylic acid, clopidogrel, prasugrel, ticagrelor, critically ill, pharmacokinetic, pharmacodynamics
- Medical subject headings
- Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
acetylsalicylic acidDrug
Also called 100mg Thrombo-ASS, 200mg Thrombo-ASS, 81mg chewable aspirin, 100mg intravenous acetylsalicylic acid
clopidogrelDrug
Also called 75mg po clopidogrel, 600mg po clopidogrel (loading dose)
prasugrelDrug
Also called 60mg prasugrel per os loading dose, 10mg prasugrel per os daily
ticagrelorDrug
Also called 180mg ticagrelor per os (loading dose)
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. Receives: 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 Receives: 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 Receives: 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 Receives: Drug: prasugrel |
| 600mg clopidogrel | Experimental | additional loading dose for 24 patients tested with high "on treatment" platelet reactivity to clopidogrel Receives: 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 Receives: Drug: ticagrelor |
| prasugrel 10mg | Active comparator | patients treated with 10mg prasugrel daily Receives: Drug: prasugrel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: on average 3 days
Secondary outcomes (5)
Prevalence of high "on-treatment" platelet reactivity in the intensive care unit
percentage of patients tested with high "on treatment" platelet reactivity according to defined values
Measured: maximum 2 weeks after admission
Evaluation of pharmacokinetics (Serum levels of Salicylate/acetylsalicylic acid, clopidogrel-active metabolite, prasugrel-active metabolite, ticagrelor active-metabolite)
Serum levels of Salicylate/acetylsalicylic acid, clopidogrel-active metabolite, prasugrel-active metabolite, ticagrelor active-metabolite
Measured: on average 3 days
intensive care unit mortality
discharge of ICU
Measured: maximum 90 days
comparison of hemodynamically stable vs unstable ((defined by serum lactate>2.1mmol/l, need for circulatory support)
hemodynamically stable vs unstable (defined by serum lactate>2.1mmol/l, need for circulatory support)
Measured: maximum 3 days
major bleeding (defined by TIMI-TRITON-38 criteria)
assessment of major bleeding incidences defined by TIMI-TRITON-38 criteria
Measured: average of 2 weeks within inclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2014 (estimated)
- Study startNov 2012
- Primary completionJul 2020 (estimated)
- Study completionAug 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Critical IllnessStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bernd Jilma, Medical University of Vienna
- Investigators
- Bernd Jilma, Ao. Univ.-Prof. Dr. med, Principal investigator, Medical University of Vienna, Department of Clinical Pharmacology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02285751
- Sponsor's protocol ID
- HTPR-ICU
- Other IDs
- 2012-002226-76
- Status last verified
- Aug 2019
- First submitted
- 24 Oct 2012
- Last updated
- 20 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High "on Treatment" Platelet Reactivity in the Intensive Care Unit
- ClinicalTrials.gov ID
- NCT02285751
- Acronym / sponsor ID
- HTPR-ICU
- Conditions
- Critical Illness
- Keywords
- high on treatment platelet reactivity, acetylsalicylic acid, clopidogrel, prasugrel, ticagrelor, critically ill, pharmacokinetic, pharmacodynamics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- Nov 2012
- Primary completion
- Jul 2020 (estimated)
- Study completion
- Aug 2020 (estimated)
- First posted
- 7 Nov 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| 200mg acetylsalicylic acid per os | Experimental | Drug: acetylsalicylic acidpatients with high "on treatment" platelet reactivity to acetylsalicylic acid are randomized to 3 different groups, one group receives 200mg acetylsalicylic acid per os |
| 100mg acetylsalicylic acid intravenous | Experimental | Drug: acetylsalicylic acidpatients with high "on treatment" platelet reactivity to acetylsalicylic acid are randomized to 3 different groups, one group receives 100mg acetylsalicylic acid intravenously. |
| 81 mg chewable acetylsalicylic acid | Experimental | Drug: acetylsalicylic acidpatients with high "on treatment" platelet reactivity to acetylsalicylic acid are randomized to 3 different groups, one group receives 81mg chewable acetylsalicylic acid |
| 75mg clopidogrel | Active comparator | Drug: clopidogrelcontrol group for patients with high "on treatment" platelet reactivity to clopidogrel patients continue with standard treatment 75mg clopidogrel/day |
| 60mg prasugrel | Experimental | Drug: prasugrelLoading 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 |
| 600mg clopidogrel | Experimental | Drug: clopidogreladditional loading dose for 24 patients tested with high "on treatment" platelet reactivity to clopidogrel |
| 180mg ticagrelor | Experimental | Drug: ticagrelorLoading 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 |
| prasugrel 10mg | Active comparator | Drug: prasugrelpatients treated with 10mg prasugrel daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- >18years of age
- admittance to an intensive care unit
Key exclusion criteria (7 listed)
- recent surgery
- active bleeding
- known coagulation disorders
- discretion of the physician
- terminal illness (anticipated life expectancy < 3months; e.g. due to cancer)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| acetylsalicylic acidAlso: 100mg Thrombo-ASS, 200mg Thrombo-ASS, 81mg chewable aspirin, 100mg intravenous acetylsalicylic acid | Drug | 100mg acetylsalicylic acid intravenous, 200mg acetylsalicylic acid per os, 81 mg chewable acetylsalicylic acid |
| clopidogrelAlso: 75mg po clopidogrel, 600mg po clopidogrel (loading dose) | Drug | 600mg clopidogrel, 75mg clopidogrel |
| prasugrelAlso: 60mg prasugrel per os loading dose, 10mg prasugrel per os daily | Drug | 60mg prasugrel, prasugrel 10mg |
| ticagrelorAlso: 180mg ticagrelor per os (loading dose) | Drug | 180mg ticagrelor |
Primary outcome
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
5 secondary outcomes
Prevalence of high "on-treatment" platelet reactivity in the intensive care unit
Time frame: maximum 2 weeks after admission
Evaluation of pharmacokinetics (Serum levels of Salicylate/acetylsalicylic acid, clopidogrel-active metabolite, prasugrel-active metabolite, ticagrelor active-metabolite)
Time frame: on average 3 days
intensive care unit mortality
Time frame: maximum 90 days
comparison of hemodynamically stable vs unstable ((defined by serum lactate>2.1mmol/l, need for circulatory support)
Time frame: maximum 3 days
major bleeding (defined by TIMI-TRITON-38 criteria)
Time frame: average of 2 weeks within inclusion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2019.
Related trials for Critical Illness
RecruitingPhase 4
A Study to Compare the Efficacy and Safety of Extended and Intermittent Infusion of Beta-lactams in Critically Ill Paediatric Patients
Infection, Sepsis
Recruiting
Development and Preliminary Validation of Intelligent Video Laryngoscope for Emergency Use
Critically Ill Patients Requiring Mechanical Ventilation
Active, not recruiting
Weighted Blankets for Agitation in Adults in the Intensive Care Unit
Psychomotor Agitation, Critical Illness
Not yet recruitingObservational study
Core Competencies in General Intensive Care Ultrasound (GenIUS): a Delphi Study
Critical Illness, Ultrasound
RecruitingObservational study
Predicting Extubation Failure Using Machine Learning
Extubation Failure, Critical Illness
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bernd Jilma, Ao. Univ.-Prof. Dr. med principal investigator
Medical University of Vienna, Department of Clinical Pharmacology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing acetylsalicylic acid, clopidogrel and prasugrel in people with Critical Illness, run by Medical University of Vienna at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Bernd Jilma, Ao. Univ.-Prof. Dr. med. (0043140400 ext. 2981, bernd.jilma@meduniwien.ac.at), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pharmacodynamics (Arachidonic acid induced aggregation test with multiplate electrode aggregometry) (time frame: on average 3 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2019.