The Effect of Ticagrelor With or Without Atorvastatin on Endothelial Function in Healthy Males

A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Effect of Atorvastatin Treatment for 14 Days in Combination With an Acute Dose of Ticagrelor on Ischemia Reperfusion Induced Endothelial Dysfunction of the Forearm Vasculature in Healthy Male Subjects

To test the effect of atorvastatin or placebo in combination with ticagrelor on ACh-induced vasodilatation of the forearm resistance vasculature as assessed by forearm blood flow (FBF) measurement before and 10 min after a 20 min forearm ischemia. The area under the dose-effect curve (AUC) of different ACh doses will be calculated and compared between treatment groups (atorvastatin + ticagrelor vs. placebo + ticagrelor) and different time points (pre-ischemia vs. post-ischemia).

Study Overview

• Status: Completed
• Conditions: Ischemia
• Intervention / Treatment: Drug: Ticagrelor; Drug: Atorvastatin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 4

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University of Vienna, Department of Clinical Pharmacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male subjects; 18 - 40 years of age
• Body mass index between 18 and 27 kg/m2
• Written informed consent
• Normal findings in medical & bleeding history
• Non-smoking

Exclusion Criteria:

• Regular intake of any medication including OTC drugs and herbals within 2 weeks before IMP administration
• Known coagulation disorders (e.g. haemophilia, von Willebrand´s disease)
• Known disorders with increased bleeding risk (e.g. peridontosis, haemorrhoids, acute gastritis, peptic ulcer, intestinal ulcer)
• Known sensitivity to common causes of bleeding (e.g. nasal)
• History of thromboembolism
• History of occlusive vascular diseases
• History of vascular anomalies
• History of hypercholesterolemia
• History of myopathy
• Impaired liver function (AST, ALT, gGT, bilirubin > 3 x ULN)
• Impaired renal function (serum creatinine > 1.3 mg/dl)
• Elevated creatinine-kinase or serum-myoglobin (> 3 x ULN)
• Any other relevant deviation from the normal range in clinical chemistry, haematology or urine analysis
• HIV-1/2-Ab, HbsAg or HCV-Ab positive serology
• Systolic blood pressure above 145 mmHg, diastolic blood pressure above 95 mmHg
• Known allergy against any test agent under study
• Regular daily consumption of more than on litre of xanthine-containing beverages or more than 40g alcohol
• Participation in another clinical trial during the preceding 3 weeks

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Atorvastatin; 80 mg atorvastatin for 14 days with a loading dose of 180 mg ticagrelor on day 15	Drug: Ticagrelor; Drug: Atorvastatin; Subjects will receive 80 mg atorvastatin once daily for 14 days (until study day 15). On study day 15, 80 mg atorvastatin in combination with a loading dose of 180 mg ticagrelor will be administered.
PLACEBO_COMPARATOR: Placebo; Placebo for 14 days with a loading dose of 180 mg ticagrelor on day 15	Drug: Ticagrelor; Drug: Placebo; Subjects will receive placebo once daily for 14 days (until study day 15). On study day 15, placebo in combination with a loading dose of 180 mg ticagrelor will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve (AUC) of Forearm blood flow (FBF) measurements of Acetylcholine (ACh) induced vasodilatation	To test the effect of atorvastatin or placebo in combination with ticagrelor on ACh-induced vasodilatation of the forearm resistance vasculature as assessed by FBF measurement before and 10 min after a 20 min forearm ischemia	Change of the AUC before and 10 min after forearm ischemia

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve (AUC) of Forearm blood flow (FBF) measurements of Glyceryltrinitrate (GTN) induced vasodilatation	To test the effect of atorvastatin or placebo in combination with ticagrelor on GTN-induced vasodilatation of the forearm resistance vasculature as assessed by FBF measurement before and 10 min after a 20 min forearm ischemia	Change of the AUC before and 10 min after forearm ischemia

Collaborators and Investigators

• Sponsor: Medical University of Vienna

Publications and helpful links

General Publications

• Weisshaar S, Litschauer B, Kerbel T, Wolzt M. Atorvastatin combined with ticagrelor prevent ischemia-reperfusion induced vascular endothelial dysfunction in healthy young males - A randomized, placebo-controlled, double-blinded study. Int J Cardiol. 2018 Mar 15;255:1-7. doi: 10.1016/j.ijcard.2017.12.067. Epub 2017 Dec 24.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2016
• Primary Completion (ACTUAL): February 1, 2017
• Study Completion (ACTUAL): March 1, 2017

Study Registration Dates

• First Submitted: September 19, 2016
• First Submitted That Met QC Criteria: September 21, 2016
• First Posted (ESTIMATE): September 22, 2016

Study Record Updates

• Last Update Posted (ACTUAL): March 22, 2017
• Last Update Submitted That Met QC Criteria: March 21, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Ischemia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ticagrelor; Atorvastatin
• Other Study ID Numbers: FBF-Statin-Tica

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED