A Study of the Effect of Epinephrine on Platelet Reactivity in Subjects Treated With Ticagrelor
Condition: Healthy Volunteers
Study type: Interventional
Phase: Phase 1

Summary: 
      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).
    

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.
    

Intervention name(s): Ticagrelor 90mg; Epinephrine; Metoprolol
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 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.; 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.; 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.
Intervention MeSH terms: Metoprolol; Epinephrine; Ticagrelor
Intervention model: Single Group Assignment
Intervention model 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).
Masking: None (Open Label)
Primary purpose: Supportive Care