Hunting for the Off-Target Properties of Ticagrelor on Endothelial Function in Humans (HI-TECH)

NCT02587260 | Completed Phase 4

• 2 other identifiers: NL51124.078.142014-004189-64
• Study Type: interventional
• Target: 54
• Locations: 4 countries
• Sites: 5

Brief Summary

The purpose of this randomized, cross-over study, is to ascertain if ticagrelor, but not prasugrel or clopidogrel, is associated to an improved endothelial function as assessed with peripheral arterial tonometry and markers of endothelial function measurement in post-ACS patients.

Conditions

Cardiovascular Diseases

Keywords

P2Y12 inhibitors; Acute Coronary Syndrome (ACS); Endothelial function; Adenosine measurement in human subject; Endopath

Outcome Measures

Primary Outcomes (1)

• Improvement of endothelial function at steady state

  Evaluation if ticagrelor, at steady state (i.e. after 30 day therapy), will be associated to an improved endothelial function as compared to clopidogrel or prasugrel when assessed with endopath system 1-2 hour(s) after maintenance drug intake.

  After 30 days of therapy with assigned P2Y12-inhibitor

Secondary Outcomes (1)

• Improvement of endothelial function, both acutely and at steady state

  One or 2 hour(s) after P2Y12-inhibitor loading dose administration and before and 1 or 2 hour(s) after maintenance dose administration

Study Arms (6)

Sequence I

ACTIVE COMPARATOR

Ticagrelor in the period I Prasugrel in the period II Clopidogrel in the period III

Drug: Ticagrelor; Drug: Prasugrel; Drug: Clopidogrel

Sequence II

ACTIVE COMPARATOR

Ticagrelor in the period I Clopidogrel in the period II Prasugrel in the period III

Drug: Ticagrelor; Drug: Prasugrel; Drug: Clopidogrel

Sequence III

ACTIVE COMPARATOR

Prasugrel in the period I Ticagrelor in the period II Clopidogrel in the period III

Drug: Ticagrelor; Drug: Prasugrel; Drug: Clopidogrel

Sequence IV

ACTIVE COMPARATOR

Prasugrel in the period I Clopidogrel in the period II Ticagrelor in the period III

Drug: Ticagrelor; Drug: Prasugrel; Drug: Clopidogrel

Sequence V

ACTIVE COMPARATOR

Clopidogrel in the period I Ticagrelor in the period II Prasugrel in the period III

Drug: Ticagrelor; Drug: Prasugrel; Drug: Clopidogrel

Sequence VI

ACTIVE COMPARATOR

Clopidogrel in the period I Prasugrel in the period II Ticagrelor in the period III

Drug: Ticagrelor; Drug: Prasugrel; Drug: Clopidogrel

Interventions

Ticagrelor DRUG

Comparison of ticagrelor with respect to prasugrel and clopidogrel in a different sequence

Also known as: Brilique

Sequence I; Sequence II; Sequence III; Sequence IV; Sequence V; Sequence VI

Prasugrel DRUG

Comparison of ticagrelor with respect to prasugrel and clopidogrel in a different sequence

Also known as: Efient

Sequence I; Sequence II; Sequence III; Sequence IV; Sequence V; Sequence VI

Clopidogrel DRUG

Comparison of ticagrelor with respect to prasugrel and clopidogrel in a different sequence

Also known as: Plavix

Sequence I; Sequence II; Sequence III; Sequence IV; Sequence V; Sequence VI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients older than 18 years.
• Patients who experienced an Acute Coronary Syndrome (including STEMI or NSTEMI) at least 30 days before.
• Patients on ongoing treatment for at least 30 days with dual anti-platelet therapy consisting of aspirin, at doses of 75-160 mg daily and one commercially available P2Y12 oral inhibitor , including ticagrelor, clopidogrel or prasugrel.
• Patients who remained free from bleeding (defined as BARC type 2 or greater) or ischemic recurrences.

You may not qualify if:

• Administration of fibrinolytics or glycoprotein IIb/IIIa inhibitors in the previous 30 days.
• Major surgery within 30 days or any planned surgical or percutaneous intervention.
• Active bleeding or previous clinical relevant bleeding or stroke in the last 6 months.
• Previous transient ischemic attack or intracranial bleeding.
• Thrombocytopenia.
• Oral anticoagulant therapy.
• Vasculitis or any know immunological disorder.
• Severe hepatic failure.
• Uncontrolled hypertension (systolic or diastolic arterial pressure \>180 mmHg or 120, respectively, despite medical therapy).
• Known intolerance to aspirin or to clopidogrel or prasugrel or ticagrelor.
• Limited life expectancy, e.g. neoplasms, others.
• Inability to obtain informed consent.
• Pregnancy.

Sponsors & Collaborators

• Erasmus Medical Center: lead
• Covance: collaborator

Study Sites (5)

Policlinico San Matteo

Pavia, 27100, Italy

Location

VU Medical Center

Amsterdam, 1081 HZ, Netherlands

Location

Erasmus MC

Rotterdam, 3015 CE, Netherlands

Location

Hospital Clinic

Barcelona, 08036, Spain

Location

Inselspitäl University Medical Center

Bern, 3010, Switzerland

Location

Related Publications (8)

• Hochberg Y, Benjamini Y. More powerful procedures for multiple significance testing. Stat Med. 1990 Jul;9(7):811-8. doi: 10.1002/sim.4780090710.

  PMID: 2218183 BACKGROUND

• Flammer AJ, Anderson T, Celermajer DS, Creager MA, Deanfield J, Ganz P, Hamburg NM, Luscher TF, Shechter M, Taddei S, Vita JA, Lerman A. The assessment of endothelial function: from research into clinical practice. Circulation. 2012 Aug 7;126(6):753-67. doi: 10.1161/CIRCULATIONAHA.112.093245.

  PMID: 22869857 RESULT

• Cattaneo M, Schulz R, Nylander S. Adenosine-mediated effects of ticagrelor: evidence and potential clinical relevance. J Am Coll Cardiol. 2014 Jun 17;63(23):2503-2509. doi: 10.1016/j.jacc.2014.03.031. Epub 2014 Apr 23.

  PMID: 24768873 RESULT

• Bonello L, Laine M, Kipson N, Mancini J, Helal O, Fromonot J, Gariboldi V, Condo J, Thuny F, Frere C, Camoin-Jau L, Paganelli F, Dignat-George F, Guieu R. Ticagrelor increases adenosine plasma concentration in patients with an acute coronary syndrome. J Am Coll Cardiol. 2014 Mar 11;63(9):872-7. doi: 10.1016/j.jacc.2013.09.067. Epub 2013 Nov 27.

  PMID: 24291273 RESULT

• Torngren K, Ohman J, Salmi H, Larsson J, Erlinge D. Ticagrelor improves peripheral arterial function in patients with a previous acute coronary syndrome. Cardiology. 2013;124(4):252-8. doi: 10.1159/000347122. Epub 2013 Apr 9.

  PMID: 23594617 RESULT

• McCrea CE, Skulas-Ray AC, Chow M, West SG. Test-retest reliability of pulse amplitude tonometry measures of vascular endothelial function: implications for clinical trial design. Vasc Med. 2012 Feb;17(1):29-36. doi: 10.1177/1358863X11433188.

  PMID: 22363016 RESULT

• Ariotti S, Ortega-Paz L, van Leeuwen M, Brugaletta S, Leonardi S, Akkerhuis KM, Rimoldi SF, Janssens G, Gianni U, van den Berge JC, Karagiannis A, Windecker S, Valgimigli M; HI-TECH Investigators. Effects of Ticagrelor, Prasugrel, or Clopidogrel on Endothelial Function and Other Vascular Biomarkers: A Randomized Crossover Study. JACC Cardiovasc Interv. 2018 Aug 27;11(16):1576-1586. doi: 10.1016/j.jcin.2018.04.022. Epub 2018 May 24.

  PMID: 29805112 DERIVED

• Ariotti S, van Leeuwen M, Brugaletta S, Leonardi S, Akkerhuis KM, Rimoldi SF, Janssens GN, Ortega-Paz L, Gianni U, van den Berge JC, Karagiannis A, Windecker S, Valgimigli M; HI-TECH Investigators. Effects of Ticagrelor, Prasugrel, or Clopidogrel at Steady State on Endothelial Function. J Am Coll Cardiol. 2018 Mar 20;71(11):1289-1291. doi: 10.1016/j.jacc.2018.01.027. No abstract available.

  PMID: 29544613 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases; Acute Coronary Syndrome

Interventions

Ticagrelor; Prasugrel Hydrochloride; Clopidogrel

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Thiophenes; Sulfur Compounds; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Ticlopidine; Thienopyridines; Pyridines

Study Officials

• Marco Valgimigli, MD, PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Coordinating Investigator/Project Leader

Model Details: Latin square design

Study Record Dates

• First Submitted: October 23, 2015
• First Posted: October 27, 2015
• Study Start: December 17, 2015
• Primary Completion: February 10, 2017
• Study Completion: February 10, 2017
• Last Updated: February 13, 2017

Record last verified: 2017-02

Locations

ES (1); NL (2); IT (1); CH (1)