The Efficacy of Ticagrelor on Abdominal Aortic Aneurysm (AAA) Expansion (TicAAA)

Does Ticagrelor Inhibit Growth of Small Abdominal Aortic Aneurysms? A Randomised Controlled Trial (TicAAA)

Abdominal aortic aneurysm (AAA) is a major health problem and ruptured AAA is a common cause of death in Europe and North America. A key limitation of contemporary treatment strategies of AAA is the lack of therapy directed at reducing expansion. Although surgical repair is an effective treatment for large AAA, it is associated with significant mortality and morbidity as well as substantial cost. The rationale for this randomized controlled study is to investigate whether treatment with Ticagrelor inhibits growth of small abdominal aortic aneurysms.

Study Overview

• Status: Completed
• Conditions: Abdominal Aortic Aneurysm
• Intervention / Treatment: Drug: Placebo; Drug: Ticagrelor

• Study Type: Interventional
• Enrollment (Actual): 145
• Phase: Phase 2

Contacts and Locations

Study Locations

• Sweden
  • Uppsala, Sweden, SE-751 85
    • Department of Surgical Sciences/Vascular Surgery, Uppsala University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provision of written informed consent
• Male and female patients
• Age 50-85 years
• Documented infrarenal aortic aneurysm between 35-49 mm
• Acetylsalicylic acid (ASA)-naïve

Exclusion Criteria:

• Short expected survival.
• On anti-platelet therapy.
• On long-term oral or parenteral anticoagulant treatment.
• On strong inhibitors of CYP3A enzyme (Ketoconazole, Itraconazole, Voriconazole, Telithromycin, Clarithromycin, Ritonavir, Saquinavir, Nelfinavir, Indinavir, Atazanavir).
• On CYP3A (Cytochrome P450, family 3, subfamily A) substrates or inducers >40mg daily doses (Simvastatin, Lovastatin, Rifampin/rifampicin, Phenytoin, Carbamazepine, Phenobarbital).
• Known or suspected connective tissue disorder (Marfans syndrome, etc), infected or inflammatory aneurysm, aneurysm post aortic dissection or previous surgery of the infrarenal aorta.
• Increased risk for bradycardia or ongoing treatment with any bradycardia inducing drug.
• Contraindication for Ticagrelor; hypersensitivity to Ticagrelor or any of the excipients, active pathological bleeding, history of intracranial hemorrhage, moderate or severe hepatic impairment (eg, ascites and/or clinical signs of coagulopathy), on haemodialysis.
• Known haemostatic or coagulation disorder, gastrointestinal bleeding within the past 6 months, or increased bleeding risk due to surgery or trauma within 30 days.
• MRI exclusion criteria, such as: severe claustrophobia, pacemaker, metallic implants in brain, cochlear implants.
• Metallic implants in aortic region.
• Enrolled in either another investigational drug or medical device study or another investigational study of an approved drug or medical device within 30 days prior to visit 1 of the current study.
• Any condition or laboratory finding which in the opinion of the Investigator makes the patient unsuitable for inclusion (eg, active malignancy other than squamous cell or basal cell skin cancer, long-term concomitant treatment with non-steroidal anti-inflammatory drugs (NSAIDs).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ticagrelor; Ticagrelor 90 mg tablets twice daily for 12 months.	Drug: Ticagrelor
Placebo Comparator: Placebo; Ticagrelor-placebo tablets twice daily for 12 months.	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AAA volume growth	To determine mean reduction in AAA volume growth rate (%) measured with magnetic resonance imaging (MRI) at 12 months	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AAA diameter growth, need for surgery and rupture	To determine mean reduction in diameter growth rate (mm), measured with MRI and ultra sound (US), mean reduction in thrombus volume enlargement rate (%) measured with MRI, need for surgery (≥55mm), aneurysm rupture, at 12 months	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bleeding	To determine bleeding events; primary according to BARC (Bleeding Academic Research Consortium) and secondary according to TIMI (Thrombolysis in Myocardial Infarction) Major and Minor.	12 months

Collaborators and Investigators

• Sponsor: Uppsala University
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Anders Wanhainen, MD. PhD, Uppsala University, Sweden

Publications and helpful links

General Publications

• Wanhainen A, Mani K, Kullberg J, Svensjo S, Bersztel A, Karlsson L, Holst J, Gottsater A, Linne A, Gillgren P, Langenskiold M, Hultgren R, Roy J, Gilgen NP, Ahlstrom H, Lederle FA, Bjorck M. The effect of ticagrelor on growth of small abdominal aortic aneurysms-a randomized controlled trial. Cardiovasc Res. 2020 Feb 1;116(2):450-456. doi: 10.1093/cvr/cvz133.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2014
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2017

Study Registration Dates

• First Submitted: February 21, 2014
• First Submitted That Met QC Criteria: February 21, 2014
• First Posted (Estimate): February 25, 2014

Study Record Updates

• Last Update Posted (Actual): May 2, 2018
• Last Update Submitted That Met QC Criteria: May 1, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Antiplatelet; Aneurysm; Aorta
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Aortic Diseases; Aneurysm; Aortic Aneurysm; Aortic Aneurysm, Abdominal; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor
• Other Study ID Numbers: UpAAA - 2014 - 01