A Study of the Effect of Epinephrine on Platelet Reactivity in Subjects Treated With Ticagrelor

May 3, 2018 updated by: Vastra Gotaland Region

Low Dose EPInephrine to Improve Platelet Reactivity in TICagrelor-treated Subjects: A Proof of Concept Study in Healthy Volunteers (EPITIC)

The study is an experimental observational study in ten healthy volunteers. Based on an in vitro study, it is hypothesize that a low dose epinephrine infusion will improve platelet function in healthy volunteers who have received ticagrelor. Volunteers fulfilling all of the inclusion and none of the exclusion criteria will be included. Enrollment will be continued until the required sample size is achieved (10 subjects).

Once informed consent is obtained, screening data will be collected to determine each subject's eligibility for study participation. The total expected duration of subject participation is 18 days, from screening visit to end of follow-up. The active participation is 8h (study procedure 4 hours, observation period 4 hours).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The study is an experimental observational study in ten healthy volunteers. Volunteers fulfilling all of the inclusion and none of the exclusion criteria will be included. Enrollment will be continued until the required sample size is achieved (10 subjects).

The total expected duration of subject participation is 18 days, from screening visit to end of follow-up. The active participation is 8h (study procedure 4 hours, observation period 4 hours).

The study will include four visits in total, beginning with the written informed consent at the screening visit, followed by the study visit. A phone follow-up visit is conducted the day after the treatment and after 72h to ensure subject's well-being/ inquire if the subject have had any Adverse Event (AE).

On the treatment day, an arterial catheter for continuous invasive blood pressure registration and blood sample collection will be inserted in the radial artery. In addition, a catheter for drug administration will be inserted in the brachial vein. After baseline registration (blood pressure and pulse), blood sampling and assessment of dyspnea (Borg-scale), ticagrelor is administered orally to the subjects. Two hours after administration, the registrations and blood sampling (outcome samples) are repeated after which an infusion of epinephrine is started at a weight-adjusted rate of 0.01, 0.05, 0.10 and 0.15 μg kg-1 min-1. Each infusion will be maintained for 15 minutes. At the end of each infusion period, registrations and blood sampling are repeated. The blood pressure may increase as a result of epinephrine infusion and metoprolol will therefore be administered to investigate if it affects platelet function. Hence, after the last measurement with the highest dose of epinephrine, 5 mg metoprolol (Abcur, Haelsingborg , Sweden) will be given intravenously and thereafter registrations and blood sampling will be repeated. The infusion is then stopped and the healthy volunteers are observed for 4 hours.

All study subjects will be contacted the day after treatment and three days after treatment and asked about their wellbeing/ if they have had any AEs.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Sweden
      • Gothenburg, Sweden, 41345
        • Gothia Forum CTC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 40 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  1. Signed informed consent,
  2. Males of age 18-40 years

Exclusion Criteria:

  1. Any chronic physical or mental disease or disorder
  2. Chronic medication of any kind
  3. Any occasional doses of the following substances at least one week before the investigation due to potential interactions with ticagrelor: ketoconazole, clarithromycin, nefazodone, ritonavir, atazanavir, rifampicin, fenitoin, carbamazepin, pentobarbital , cyclosporine, verapamil, diltiazem, kinidin, heparin, enoxaparin, acetylsalicylic acid, desmopressin, digoxin, beta-blockers (e.g. metoprolol, atenolol , bisoprolol) and selective serotonin reuptake inhibitors (SSRI) (e.g. paroxetine, sertraline, citalopram). In addition non-steroidal anti-inflammatory drugs (NSAIDS) should be avoided due to an increased risk of bleeding.
  4. Any occasional doses of the following substances at least one week before the investigation due to potential interactions with adrenalin: Beta-blockers ((e.g. metoprolol, atenolol , bisoprolol), tricyclic antidepressants (e.g protriptyline, maprotilin), digoxin and kinidin.
  5. Any occasional doses of the following substances at least one week before the investigation due to potential interactions with metoprolol: Calcium-antagonists (verapamil, diltiazem, nifedipine), anti-arrythmics (e.g disopyramide), insulin, tricyclic antidepressants (e.g protriptyline, maprotilin), barbiturates; fentiazins and nitroglycerine.
  6. Non-willingness to refrain from caffeine intake or nicotine use within 24 hours before start of treatment
  7. Simultaneous participation in any other clinical study
  8. Known drug abuse of any kind, or other condition that may render the subject more likely to be non-compliant to the protocol, as judged by the investigator
  9. Known intolerance or contraindication to ticagrelor, adrenaline or metoprolol
  10. Any disorder that may interfere with drug absorption
  11. Previous intracranial bleeding
  12. Any condition that in the opinion of the investigator may interfere with adherence to trial protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: SUPPORTIVE_CARE
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Ticagrelor/Epinephrine/Metoprolol

2 x 90 mg of ticagrelor will be administered orally to the subjects. Two hours after administration, the registrations and blood sampling are repeated after which an infusion of epinephrine diluted in glucose solution (5%) is started at a weight-adjusted rate of 0.01, 0.05, 0.10 and 0.15 μg kg-1 min-1. Each infusion will be maintained for 15 minutes.

After the measurement at the highest dose of epinephrine, 5 mg metoprolol (Abcur, Haelsingborg , Sweden) will be given intravenously to the study subject and thereafter registrations and blood sampling will be repeated.
Drug: Ticagrelor 90mg

2 x 90 mg of ticagrelor will be administered orally to the subjects. Two hours after administration, the registrations and blood sampling are repeated after which an infusion of epinephrine diluted in glucose solution (5%) is started at a weight-adjusted rate of 0.01, 0.05, 0.10 and 0.15 μg kg-1 min-1. Each infusion will be maintained for 15 minutes.

After the measurement at the highest dose of epinephrine, 5 mg metoprolol (Abcur, Haelsingborg , Sweden) will be given intravenously to the study subject and thereafter registrations and blood sampling will be repeated.

Drug: Epinephrine

2 x 90 mg of ticagrelor will be administered orally to the subjects. Two hours after administration, the registrations and blood sampling are repeated after which an infusion of epinephrine diluted in glucose solution (5%) is started at a weight-adjusted rate of 0.01, 0.05, 0.10 and 0.15 μg kg-1 min-1. Each infusion will be maintained for 15 minutes.

After the measurement at the highest dose of epinephrine, 5 mg metoprolol (Abcur, Haelsingborg , Sweden) will be given intravenously to the study subject and thereafter registrations and blood sampling will be repeated.

Drug: Metoprolol

2 x 90 mg of ticagrelor will be administered orally to the subjects. Two hours after administration, the registrations and blood sampling are repeated after which an infusion of epinephrine diluted in glucose solution (5%) is started at a weight-adjusted rate of 0.01, 0.05, 0.10 and 0.15 μg kg-1 min-1. Each infusion will be maintained for 15 minutes.

After the measurement at the highest dose of epinephrine, 5 mg metoprolol (Abcur, Haelsingborg , Sweden) will be given intravenously to the study subject and thereafter registrations and blood sampling will be repeated.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Platelet aggregability, Area under the aggregation curve (AUC) for adenosine diphosphate (ADP)-induced platelet aggregation
Time Frame: The primary outcome measure will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
Area under the aggregation curve (AUC) for adenosine diphosphate (ADP)-induced platelet aggregation
The primary outcome measure will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Platelet aggregability, Area under the aggregation curve (AUC) for arachidonic acid-aggregation.
Time Frame: The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
Area under the aggregation curve (AUC) for arachidonic acid-aggregation.
The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
Platelet aggregability, AUC for thrombin receptor activating peptide (TRAP)-induced aggregation.
Time Frame: The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
AUC for thrombin receptor activating peptide (TRAP)-induced aggregation.
The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
Platelet activation, Median fluorescence of platelets expressing PAC-1 (name of an antibody), unstimulated
Time Frame: The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
Median fluorescence of platelets expressing PAC-1 (name of an antibody), unstimulated
The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
Platelet activation, Percentage of platelets expressing PAC-1, unstimulated
Time Frame: The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
Percentage of platelets expressing PAC-1, unstimulated
The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
Platelet activation, Median fluorescence of platelets expressing PAC-1, ADP-induced
Time Frame: The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
Median fluorescence of platelets expressing PAC-1, ADP-induced
The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
Platelet activation, ADP-induced percentage of platelets expressing PAC-1, ADP-induced
Time Frame: The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
ADP-induced percentage of platelets expressing PAC-1, ADP-induced
The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
Platelet activation, Median fluorescence of platelets expressing P-selectin, unstimulated
Time Frame: The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
Median fluorescence of platelets expressing P-selectin, unstimulated
The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
Platelet activation, Percentage of platelets expressing P-selectin, unstimulated
Time Frame: The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
Percentage of platelets expressing P-selectin, unstimulated
The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
Platelet activation, Median fluorescence of platelets expressing P-selectin, ADP-induced
Time Frame: The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
Median fluorescence of platelets expressing P-selectin, ADP-induced
The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
Platelet activation, Percentage of platelets expressing P-selectin, ADP-induced
Time Frame: The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
Percentage of platelets expressing P-selectin, ADP-induced
The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
Coagulation parameters, EXTEM (name of a thromboelastometric test) Clotting time
Time Frame: The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
EXTEM (name of a thromboelastometric test) Clotting time
The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
Coagulation parameters, EXTEM clot formation time
Time Frame: The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
EXTEM clot formation time
The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
Coagulation parameters, EXTEM maximum clot firmness
Time Frame: The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
EXTEM maximum clot firmness
The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
Coagulation parameters, EXTEM maximum clot elasticity
Time Frame: The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
EXTEM maximum clot elasticity
The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
Coagulation parameters, FIBTEM (name of a thromboelastometric test) Maximum clot firmness
Time Frame: The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
FIBTEM (name of a thromboelastometric test) Maximum clot firmness
The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
Coagulation parameters, FIBTEM maximum clot elasticity.
Time Frame: The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.
FIBTEM maximum clot elasticity.
The secondary outcome measures will be assessed at 7 time-points during 4 hours: before ticagrelor, 2 hours after ticagrelor, after each epinephrine infusion and after metoprolol injection.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Vastra Gotaland Region

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Uppsala University
Gothia Forum - Center for Clinical Trial

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Anders Jeppsson, MD,PhD,Prof, Dep of Cardiothoracic Surgery,Sahlgrenska University Hospital,413 45 Gothenburg, Sweden

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 28, 2018

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 28, 2018

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 28, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 5, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 13, 2018

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 22, 2018

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 11, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 3, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • EudraCT 2017-003111-18

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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