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

NCT ID: NCT03441412

Last Updated: 2018-05-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-28
• Study Completion Date: 2018-03-28

Brief 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.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Ticagrelor 90mg

Intervention Type: DRUG

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.

Epinephrine

Intervention Type: DRUG

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.

Metoprolol

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Gothia Forum - Center for Clinical Trial

OTHER

Sponsor Role: collaborator

Uppsala University

OTHER

Sponsor Role: collaborator

Vastra Gotaland Region

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anders Jeppsson, MD,PhD,Prof

Role: PRINCIPAL_INVESTIGATOR

Dep of Cardiothoracic Surgery,Sahlgrenska University Hospital,413 45 Gothenburg, Sweden

Locations

gothia Forum CTC

Gothenburg, , Sweden

Countries

Sweden

References

Singh S, Damen T, Nygren A, Shams Hakimi C, Ramstrom S, Dellborg M, Lindahl TL, Hesse C, Jeppsson A. Adrenaline Improves Platelet Reactivity in Ticagrelor-Treated Healthy Volunteers. Thromb Haemost. 2019 May;119(5):735-743. doi: 10.1055/s-0039-1683461. Epub 2019 Feb 19.

Reference Type: DERIVED

PMID: 30780166 (View on PubMed)

Other Identifiers

EudraCT 2017-003111-18

Identifier Type: -

Identifier Source: org_study_id