Clinical trial NCT01347580: A 30 Day Study to Evaluate Efficacy and Safety of Pre-hospital vs. In-hospital Initiation of Ticagrelor Therapy in STEMI Patients Planned for Percutaneous Coronary Intervention (PCI)
Official title: A 30 Day International, Randomized, Parallel-group, Double-blind, Placebo-controlled Phase IV Study to Evaluate Efficacy and Safety of Pre-hospital vs. In-hospital Initiation of Ticagrelor Therapy in STEMI Patients Planned for PCI.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Myocardial Infarction
Segment Elevation Myocardial Infarction (STEMI)
Keywords: Heart attack
heart disease
cardiovascular disease
stroke
reperfusion
pre hospital settings
ticagrelor
Percutaneous Coronary Intervention
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2011-05-04
Enrollment: 1875
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to determine whether initiation of ticagrelor as early as in the ambulance setting leads to a rapid reperfusion of the infarct-related artery therefore facilitating the Percutaneous Coronary Intervention (PCI) and optimizing the outcome for the patient.

The study will assess the efficacy and safety of pre-hospital compared to in-hospital administration of ticagrelor in co-administration with aspirin, on restoring the blood flow in the occluded heart artery and improving the myocardial perfusion in patients suffering from myocardial infarction and planned to have a PCI. Patients can be randomised in either one of the 2 arms:

re-hospital ticagrelor arm: Patients will receive a loading dose of 180 mg ticagrelor for the pre-hospital administration and placebo for in-hospital administration.

or In-hospital ticagrelor arm: Patients will receive a placebo for pre-hospital administration and 180 mg ticagrelor loading dose for in-hospital administration.

Patients are initially managed by ambulance physician/personnel in pre hospital settings. They are then transferred into a Catheterization room to undergo a PCI.

After the administration of the loading dose of ticagrelor (double blind), patients will continue on ticagrelor 90 mg bid and be followed in study for 30 days post randomisation.


Eligibility criteria: Inclusion Criteria:

* Women must not be of child-bearing potential (1 year post-menopausal or surgically sterile).
* Symptoms of acute MI of more than 30 min but less than 6 hours
* New persistent ST-segment elevation ≥ 1 mm in two or more contiguous electrocardiogram (ECG) leads.

Exclusion Criteria:

* Expected time to 1st PCI balloon inflation in the hospital, from the qualifying ECG is more than 120 minutes
* Contraindication to ticagrelor (refer to SmPC)
* Concomitant medication that may increase the risk of bleeding \[e.g non steroidal anti-inflammatory drugs (NSAIDs), oral anticoagulant and / or fibrinolytics, planned or administered 24 hours before randomization\]
* Any of the following conditions in the absence of a functioning implanted pacemaker: known SSS, second or third degree AVB, or documented syncope of suspected bradycardic origin.

Primary outcomes:
measure: Thrombolysis In Myocardial Infarction (TIMI) Flow Grade 3 of MI Culprit Vessel at Initial Angiography (Co-primary Endpoint)
timeFrame: At initial angiography, pre PCI
measure: ST-segment Elevation Resolution Pre PCI ≥70% (Co-primary Endpoint)
timeFrame: Between baseline and PCI
Secondary outcomes:
measure: 1st Composite Clinical Endpoint
timeFrame: during the 30 days of treatment
measure: 2nd Composite Clinical Endpoint
timeFrame: within 30 days of study
measure: Definite Stent Thrombosis
timeFrame: during 30 days of treatment
measure: TIMI Flow Grade 3 Post -PCI
timeFrame: at coroangiography post-PCI
measure: ST Segment Elevation Resolution Post-PCI >= 70%
timeFrame: Between baseline and ECG 60 mn post-PCI
measure: Thrombotic Bail-out With GPIIb/IIIa Inhibitors at Initial PCI
timeFrame: during PCI
measure: Major Bleeds Within 48 Hours
timeFrame: within 48 hours of first dose
measure: Minor and Major Bleedings Within 48 Hours
timeFrame: within 48 hours of first dose
measure: Major Bleeds After 48 Hours
timeFrame: after 48hours post-first dose
measure: Minor and Major Bleeds After 48 Hours
timeFrame: after 48 hours post first dose
Other outcomes:
Locations:
city: Algiers
country: Algeria
facility: Research Site
city: Blida
country: Algeria
facility: Research Site
city: Herston
country: Australia
facility: Research Site
city: Southport
country: Australia
facility: Research Site
city: Woolloongabba
country: Australia
facility: Research Site
city: Graz
country: Austria
facility: Research Site
city: Innsbruck
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Halifax
country: Canada
facility: Research Site
state: Nova Scotia
city: Newmarket
country: Canada
facility: Research Site
state: Ontario
city: Scarborough
country: Canada
facility: Research Site
state: Ontario
city: Regina
country: Canada
facility: Research Site
state: Saskatchewan
city: Aalborg
country: Denmark
facility: Research Site
city: Odense C
country: Denmark
facility: Research Site
city: Århus
country: Denmark
facility: Research Site
city: Aubervilliers
country: France
facility: Research Site
city: Besançon
country: France
facility: Research Site
city: Boulogne Billancourt
country: France
facility: Research Site
city: Bourges
country: France
facility: Research Site
city: Bron
country: France
facility: Research Site
city: Chateauroux
country: France
facility: Research Site
city: Corbeil Essonnes Cedex
country: France
facility: Research Site
city: Creteil
country: France
facility: Research Site
city: Dijon
country: France
facility: Research Site
city: LAGNY SUR MARNE cedex
country: France
facility: Research Site
city: Le Chesnay
country: France
facility: Research Site
city: Le Coudray
country: France
facility: Research Site
city: Lyon Cedex 04
country: France
facility: Research Site
city: Lyon
country: France
facility: Research Site
city: MARSEILLE cedex 15
country: France
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Massy
country: France
facility: Research Site
city: Melun
country: France
facility: Research Site
city: Montauban
country: France
facility: Research Site
city: Montfermeil
country: France
facility: Research Site
city: MONTREUIL Cedex
country: France
facility: Research Site
city: Neuilly Sur Seine
country: France
facility: Research Site
city: Nimes
country: France
facility: Research Site
city: Paris Cedex 13
country: France
facility: Research Site
city: PARIS Cedex 15
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: PESSAC Cedex
country: France
facility: Research Site
city: Quincy sous Sénart
country: France
facility: Research Site
city: Rouen Cedex
country: France
facility: Research Site
city: Strasbourg
country: France
facility: Research Site
city: TOURS Cedex 9
country: France
facility: Research Site
city: TOURS cedex
country: France
facility: Research Site
city: VANNES cedex
country: France
facility: Research Site
city: Bad Friedrichshall
country: Germany
facility: Research Site
city: Bad Nauheim
country: Germany
facility: Research Site
city: Darmstadt
country: Germany
facility: Research Site
city: Esslingen
country: Germany
facility: Research Site
city: Freiburg
country: Germany
facility: Research Site
city: Gießen
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Ludwigshafen
country: Germany
facility: Research Site
city: Lüdenscheid
country: Germany
facility: Research Site
city: Mainz
country: Germany
facility: Research Site
city: Merseburg
country: Germany
facility: Research Site
city: Wuppertal
country: Germany
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Pécs
country: Hungary
facility: Research Site
city: Szeged
country: Hungary
facility: Research Site
city: Arezzo
country: Italy
facility: Research Site
city: Ascoli Piceno
country: Italy
facility: Research Site
city: Cona
country: Italy
facility: Research Site
city: Forlì
country: Italy
facility: Research Site
city: Genova
country: Italy
facility: Research Site
city: Grosseto
country: Italy
facility: Research Site
city: Massa
country: Italy
facility: Research Site
city: Seriate
country: Italy
facility: Research Site
city: Siena
country: Italy
facility: Research Site
city: Alkmaar
country: Netherlands
facility: Research Site
city: Arnhem
country: Netherlands
facility: Research Site
city: Den Bosch
country: Netherlands
facility: Research Site
city: Terneuzen
country: Netherlands
facility: Research Site
city: A Coruña
country: Spain
facility: Research Site
city: Alicante
country: Spain
facility: Research Site
city: Badalona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Hospitalet de Llobregat(Barcel
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Santiago(A Coruña)
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Vigo(Pontevedra)
country: Spain
facility: Research Site
city: Gävle
country: Sweden
facility: Research Site
city: Linköping
country: Sweden
facility: Research Site
city: Uppsala
country: Sweden
facility: Research Site
city: Örebro
country: Sweden
facility: Research Site
city: Ashford
country: United Kingdom
facility: Research Site
city: Belfast
country: United Kingdom
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: Coventry
country: United Kingdom
facility: Research Site
city: Eastbourne
country: United Kingdom
facility: Research Site
city: Hastings
country: United Kingdom
facility: Research Site
city: Middlesborough
country: United Kingdom
facility: Research Site
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Research Site
city: Norwich
country: United Kingdom
facility: Research Site
city: Sheffield
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Dr Judith Hsia, MD
role: STUDY_DIRECTOR
affiliation: Pitie Salpetriere Hospital
name: Pr Gilles Montalescot
role: PRINCIPAL_INVESTIGATOR
References:
citation: Montalescot G, van 't Hof AW, Lapostolle F, Silvain J, Lassen JF, Bolognese L, Cantor WJ, Cequier A, Chettibi M, Goodman SG, Hammett CJ, Huber K, Janzon M, Merkely B, Storey RF, Zeymer U, Stibbe O, Ecollan P, Heutz WM, Swahn E, Collet JP, Willems FF, Baradat C, Licour M, Tsatsaris A, Vicaut E, Hamm CW; ATLANTIC Investigators. Prehospital ticagrelor in ST-segment elevation myocardial infarction. N Engl J Med. 2014 Sep 11;371(11):1016-27. doi: 10.1056/NEJMoa1407024. Epub 2014 Sep 1.
citation: Lapostolle F, Van't Hof AW, Hamm CW, Stibbe O, Ecollan P, Collet JP, Silvain J, Lassen JF, Heutz WMJM, Bolognese L, Cantor WJ, Cequier A, Chettibi M, Goodman SG, Hammett CJ, Huber K, Janzon M, Merkely B, Storey RF, Ten Berg J, Zeymer U, Licour M, Tsatsaris A, Montalescot G; ATLANTIC Investigators. Morphine and Ticagrelor Interaction in Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction: ATLANTIC-Morphine. Am J Cardiovasc Drugs. 2019 Apr;19(2):173-183. doi: 10.1007/s40256-018-0305-0.
citation: Fabris E, Van't Hof A, Hamm CW, Lapostolle F, Lassen JF, Goodman SG, Ten Berg JM, Bolognese L, Cequier A, Chettibi M, Hammett CJ, Huber K, Janzon M, Merkely B, Storey RF, Zeymer U, Cantor WJ, Kerneis M, Diallo A, Vicaut E, Montalescot G; ATLANTIC investigators. Pre-hospital administration of ticagrelor in diabetic patients with ST-elevation myocardial infarction undergoing primary angioplasty: A sub-analysis of the ATLANTIC trial. Catheter Cardiovasc Interv. 2019 Jun 1;93(7):E369-E377. doi: 10.1002/ccd.27921. Epub 2018 Oct 9.
citation: Bagai A, Goodman SG, Cantor WJ, Vicaut E, Bolognese L, Cequier A, Chettibi M, Hammett CJ, Huber K, Janzon M, Lapostolle F, Lassen JF, Merkely B, Storey RF, Ten Berg JM, Zeymer U, Diallo A, Hamm CW, Tsatsaris A, El Khoury J, Van't Hof AW, Montalescot G. Duration of ischemia and treatment effects of pre- versus in-hospital ticagrelor in patients with ST-segment elevation myocardial infarction: Insights from the ATLANTIC study. Am Heart J. 2018 Feb;196:56-64. doi: 10.1016/j.ahj.2017.10.021. Epub 2017 Nov 4.
citation: Kilic S, Fabris E, Van't Hof AWJ, Hamm CW, Lapostolle F, Lassen JF, Tsatsaris A, Diallo A, Vicaut E, Montalescot G; ATLANTIC Investigators. Thrombus aspiration and prehospital ticagrelor administration in ST-elevation myocardial infarction: Findings from the ATLANTIC trial. Am Heart J. 2018 Feb;196:1-8. doi: 10.1016/j.ahj.2017.09.018. Epub 2017 Oct 3.
citation: Venetsanos D, Sederholm Lawesson S, Alfredsson J, Janzon M, Cequier A, Chettibi M, Goodman SG, Van't Hof AW, Montalescot G, Swahn E. Association between gender and short-term outcome in patients with ST elevation myocardial infraction participating in the international, prospective, randomised Administration of Ticagrelor in the catheterisation Laboratory or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery (ATLANTIC) trial: a prespecified analysis. BMJ Open. 2017 Sep 21;7(9):e015241. doi: 10.1136/bmjopen-2016-015241.
citation: Cayla G, Lapostolle F, Ecollan P, Stibbe O, Benezet JF, Henry P, Hammett CJ, Lassen JF, Storey RF, Ten Berg JM, Hamm CW, Van't Hof AW, Montalescot G; ACTION study group. Pre-hospital ticagrelor in ST-segment elevation myocardial infarction in the French ATLANTIC population. Int J Cardiol. 2017 Oct 1;244:49-53. doi: 10.1016/j.ijcard.2017.06.009. Epub 2017 Jun 9.
citation: Lupi A, Schaffer A, Lazzero M, Tessitori M, De Martino L, Rognoni A, Bongo AS, Porto I. Pre-hospital ticagrelor in patients with ST-segment elevation myocardial infarction with long transport time to primary PCI facility. Cardiovasc Revasc Med. 2016 Dec;17(8):528-534. doi: 10.1016/j.carrev.2016.08.005. Epub 2016 Aug 20.
citation: Silvain J, Storey RF, Cayla G, Esteve JB, Dillinger JG, Rousseau H, Tsatsaris A, Baradat C, Salhi N, Hamm CW, Lapostolle F, Lassen JF, Collet JP, Ten Berg JM, Van't Hof AW, Montalescot G. P2Y12 receptor inhibition and effect of morphine in patients undergoing primary PCI for ST-segment elevation myocardial infarction. The PRIVATE-ATLANTIC study. Thromb Haemost. 2016 Aug 1;116(2):369-78. doi: 10.1160/TH15-12-0944. Epub 2015 May 19.
citation: Montalescot G, van 't Hof AW, Bolognese L, Cantor WJ, Cequier A, Chettibi M, Collet JP, Goodman SG, Hammett CJ, Huber K, Janzon M, Lapostolle F, Lassen JF, Licour M, Merkely B, Salhi N, Silvain J, Storey RF, Ten Berg JM, Tsatsaris A, Zeymer U, Vicaut E, Hamm CW; ATLANTIC Investigators. Effect of Pre-Hospital Ticagrelor During the First 24 h After Primary Percutaneous Coronary Intervention in Patients With ST-Segment Elevation Myocardial Infarction: The ATLANTIC-H(2)(4) Analysis. JACC Cardiovasc Interv. 2016 Apr 11;9(7):646-56. doi: 10.1016/j.jcin.2015.12.024. Epub 2016 Mar 5.
citation: Montalescot G, Lassen JF, Hamm CW, Lapostolle F, Silvain J, ten Berg JM, Cantor WJ, Goodman SG, Licour M, Tsatsaris A, van't Hof AW. Ambulance or in-catheterization laboratory administration of ticagrelor for primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: rationale and design of the randomized, double-blind Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery (ATLANTIC) study. Am Heart J. 2013 Apr;165(4):515-22. doi: 10.1016/j.ahj.2012.12.015. Epub 2013 Feb 13.