Clinical trial NCT02910778: The Effect of Ticagrelor With or Without Atorvastatin on Endothelial Function in Healthy Males
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Ischemia
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2016-09-22
Enrollment: 32
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Area under the curve (AUC) of Forearm blood flow (FBF) measurements of Acetylcholine (ACh) induced vasodilatation
timeFrame: Change of the AUC before and 10 min after forearm ischemia
Secondary outcomes:
measure: Area under the curve (AUC) of Forearm blood flow (FBF) measurements of Glyceryltrinitrate (GTN) induced vasodilatation
timeFrame: Change of the AUC before and 10 min after forearm ischemia
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna, Department of Clinical Pharmacology
Study officials:
References:
citation: 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.