Clinical trial NCT01149044: A Trial of Routine Aspiration Thrombectomy With Percutaneous Coronary Intervention (PCI) Versus PCI Alone in Patients With ST-Segment Elevation Myocardial Infarction (STEMI) Undergoing Primary PCI
Official title: TOTAL Trial: A Randomized Trial of Routine Aspiration ThrOmbecTomy With PCI Versus PCI ALone in Patients With STEMI Undergoing Primary PCI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Coronary Syndrome
ST Elevation Myocardial Infarction
Percutaneous Coronary Intervention
Keywords: Acute Coronary Syndrome
PCI
Percutaneous Coronary Intervention
STEMI
Thrombectomy
Lead sponsor: Population Health Research Institute
Sponsor class: OTHER
First posted: 2010-06-23
Enrollment: 10732
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an international, randomized, controlled, parallel group study in which patients with ST-Segment Elevation Myocardial Infarction (STEMI) will be allocated to one of the following: Manual aspiration thrombectomy with Percutaneous Coronary Intervention (PCI) or PCI alone.

Detailed description: The hypothesis for TOTAL is that the routine use of manual aspiration thrombectomy with an aspiration catheter (Export®) with PCI compared to PCI alone will reduce the incidence of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or new or worsening NYHA Class IV heart failure (HF) at 180 days in patients with STEMI undergoing primary PCI.

Eligibility criteria: Inclusion Criteria:

1. Patients presenting with:

   * Symptoms of myocardial ischemia lasting for ≥ 30 minutes AND
   * Definite ECG changes indicating STEMI: ST elevation of greater than 0.1 mV in two contiguous limb leads or 0.2 mV in two contiguous precordial leads
2. Referred for primary PCI
3. Randomized within 12 hours of symptoms onset and prior to diagnostic angiography
4. Informed consent

Exclusion Criteria:

1. Age ≤ 18 years
2. Prior coronary artery bypass surgery (CABG)
3. Life expectancy less than six months due to non-cardiac condition
4. Treatment with fibrinolytic therapy for qualifying index STEMI event

Primary outcomes:
measure: The first occurrence of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or new or worsening NYHA Class IV heart failure
timeFrame: up to 180 days
Secondary outcomes:
measure: Stroke
timeFrame: up to 30 days
measure: Key Net Benefit Outcome: The first occurence of CV death, MI, stroke, cardiogenic shock or new or worsening NHYA Class IV heart failure
timeFrame: up to 1 year
measure: Cardiovascular Mortality
timeFrame: up to 180 days
measure: Key Secondary Efficacy Outcome: The first occurence of cardiovascular death, myocardial infarction, cardiogenic shock, new or worsening NYHA class IV heart failure, stent thrombosis and target vessel revascularization
timeFrame: up to 180 days
Other outcomes:
measure: Primary outcome at 30 days and 1 year
timeFrame: up to 1 year
measure: Components of primary outcome and secondary outcomes
timeFrame: up to 1 year
measure: All-cause mortality
timeFrame: up to 1 year
measure: Composite of CV death, MI, cardiogenic shock, or new or worsening NYHA class IV heart failure at 30 days, 180 days
timeFrame: up to 180 days
measure: TIMI flow rates, no reflow
timeFrame: up to 1 year
measure: Stent thrombosis
timeFrame: up to 1 year
measure: Distal embolization
timeFrame: up to 1 year
measure: Left main thrombus as a complication of the PCI procedure
timeFrame: up to 1 year
measure: Target Vessel dissection
timeFrame: up to 1 year
measure: Left main dissection
timeFrame: up to 1 year
measure: Major Bleeding
timeFrame: up to 1 year
Locations:
city: Bakersfield
country: United States
facility: Central Cardiology medical Clinic
state: California
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Albuquerque
country: United States
facility: University of New Mexico Health Sciences Center
state: New Mexico
city: Cincinnati
country: United States
facility: Lindner Research Center at Christ Hospital
state: Ohio
city: Allentown
country: United States
facility: Lehigh Valley Hospital
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Clinic
state: Pennsylvania
city: Pittsburgh
country: United States
facility: WPAHS - Allegheny General Hospital
state: Pennsylvania
city: Scranton
country: United States
facility: Northeast Clinical Trials Group
state: Pennsylvania
city: Sydney
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Sydney
country: Australia
facility: St. George Public Hospital
state: New South Wales
city: Southport
country: Australia
facility: Gold Coast Hospital
state: Queensland
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Lige
country: Belgium
facility: CHR de la Citadelle
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas - PUCRS
state: RS
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericórdia de Porto Alegre
state: RS
city: Blumenau
country: Brazil
facility: Hospital Santa Isabel
state: Santa Catarina
city: Marilia
country: Brazil
facility: Santa Casa de Marilia
state: Sao Paulo
city: Sao Jose do Rio Preto
country: Brazil
facility: Fundação Faculdade de Medicina de São José do Rio Preto
state: Sao Paulo
city: Porto Elegre
country: Brazil
facility: Hospital Mae de Deus
city: Sao Paulo
country: Brazil
facility: Instituto Dante Pazzanese de Cardiologia
city: Edmonton
country: Canada
facility: Royal Alexandra Hospital
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Victoria
country: Canada
facility: Victoria Heart Institute
state: British Columbia
city: Westminster
country: Canada
facility: Royal Columbian Hospital
state: British Columbia
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Newmarket
country: Canada
facility: York PCI Group - Southlake Regional
state: Ontario
city: Scarborough
country: Canada
facility: Scarborough Cardiology Research
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Chicoutimi
country: Canada
facility: CSSS de Chicoutimi
state: Quebec
city: Montreal
country: Canada
facility: MUHC Royal Victoria Hospital
state: Quebec
city: Quebec City
country: Canada
facility: Quebec Heart Lung Insitute
state: Quebec
city: Shanghai
country: China
facility: Shanghai Gongli Hospital
city: Shanghai
country: China
facility: The First People's Hospital, Jiatong University
city: Shanghai
country: China
facility: The Tenth People's Hospital Tongji University
city: Shanghai
country: China
facility: Yueyang Hospital Shanghai University of TCM
city: Liberec
country: Czech Republic
facility: Krasjska Nemocnice Liberec
city: Pilsen
country: Czech Republic
facility: University Hospital Pilsen
city: Prague
country: Czech Republic
facility: University Hospital Motol
city: Praha
country: Czech Republic
facility: University Hospital Kralovske Vinohrady
city: Usti nad Labem
country: Czech Republic
facility: Masaryk Hospital
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Tampere
country: Finland
facility: Heart Center, Tampere University Hospital
city: Besancon
country: France
facility: Chu Jean Minjoz
city: Grenoble
country: France
facility: CHU Albert Michallon
city: Paris
country: France
facility: Hopital Bichat
city: Paris
country: France
facility: Hopital Lariboisiere Ap-HP
city: Pau
country: France
facility: Centre Hospitalier de Pau
city: Bonn
country: Germany
facility: Universitatsklinikum Bonn
city: Essen
country: Germany
facility: Elisabeth-Krankenhaus Essen
city: Immenstadt
country: Germany
facility: Clinical Association Oberallgaeu-Kempten
city: Munchen
country: Germany
facility: Klinikum der Universitat Munchen
city: Patras
country: Greece
facility: Patras University Hospital
city: Thessaloniki
country: Greece
facility: Ahepa University Hospital
city: Budapest
country: Hungary
facility: Semmelweis University Heart and Vascular Center
city: Szeged
country: Hungary
facility: University of Szeged
city: Cheonan
country: Korea, Republic of
facility: Soonchunhyang University Cheonan Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung-Hee University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul Boramae Medical Center
city: Skopje
country: Macedonia, The Former Yugoslav Republic of
facility: Medical University Skopje
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
city: Baldona
country: Spain
facility: Hospital Universitari Germans Trias I Pujol
city: Barcelona
country: Spain
facility: Complexo Hospitalario A Coruna
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: University Hospital La Paz
city: Palma de Mallorca
country: Spain
facility: Hospital Son Espases
city: Vigo
country: Spain
facility: Hospital Clinico Universitario de Vigo
city: Basingstoke
country: United Kingdom
facility: Hampshire Hospitals NHS Fuondation Trust
city: Bethnal Green
country: United Kingdom
facility: Barts and The London Heart and Chest Centre
city: Camberley
country: United Kingdom
facility: Frimley Park Hospital, NHS Foundation Trust
city: Hull
country: United Kingdom
facility: Hull and East Yorkshire Hospitals
city: Kettering
country: United Kingdom
facility: Kettering General Hospital
city: Leicester
country: United Kingdom
facility: Glenfield General Hospital
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary
city: Manchester
country: United Kingdom
facility: University Hospital South Manchester
city: Margate
country: United Kingdom
facility: Queen Elizabeth the Queen Mother Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals
city: Southampton
country: United Kingdom
facility: University Hospital Southampton
city: Taunton
country: United Kingdom
facility: Musgrove Park Hospital
Study officials:
affiliation: Hamilton Health Sciences Corporation
name: Sanjit S. Jolly, MD, MSc, FRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: Peter Munk Cardiac Centre, University Health Network
name: Vladimir Džavík, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jolly SS, Cairns J, Yusuf S, Meeks B, Shestakovska O, Thabane L, Niemela K, Steg PG, Bertrand OF, Rao SV, Avezum A, Cantor WJ, Pancholy SB, Moreno R, Gershlick A, Bhindi R, Welsh RC, Cheema AN, Lavi S, Rokoss M, Dzavik V. Design and rationale of the TOTAL trial: a randomized trial of routine aspiration ThrOmbecTomy with percutaneous coronary intervention (PCI) versus PCI ALone in patients with ST-elevation myocardial infarction undergoing primary PCI. Am Heart J. 2014 Mar;167(3):315-321.e1. doi: 10.1016/j.ahj.2013.12.002. Epub 2013 Dec 14.
citation: Jolly SS, Cairns JA, Yusuf S, Meeks B, Pogue J, Rokoss MJ, Kedev S, Thabane L, Stankovic G, Moreno R, Gershlick A, Chowdhary S, Lavi S, Niemela K, Steg PG, Bernat I, Xu Y, Cantor WJ, Overgaard CB, Naber CK, Cheema AN, Welsh RC, Bertrand OF, Avezum A, Bhindi R, Pancholy S, Rao SV, Natarajan MK, ten Berg JM, Shestakovska O, Gao P, Widimsky P, Dzavik V; TOTAL Investigators. Randomized trial of primary PCI with or without routine manual thrombectomy. N Engl J Med. 2015 Apr 9;372(15):1389-98. doi: 10.1056/NEJMoa1415098. Epub 2015 Mar 16.
citation: Alkhalil M, Kuzemczak M, Zhao R, Kavvouras C, Cantor WJ, Overgaard CB, Lavi S, Sharma V, Chowdhary S, Stankovic G, Kedev S, Bernat I, Bhindi R, Sheth T, Niemela K, Jolly SS, Dzavik V. Prognostic Role of Residual Thrombus Burden Following Thrombectomy: Insights From the TOTAL Trial. Circ Cardiovasc Interv. 2022 May;15(5):e011336. doi: 10.1161/CIRCINTERVENTIONS.121.011336. Epub 2022 May 17.
citation: Moxham R, Dzavik V, Cairns J, Natarajan MK, Bainey KR, Akl E, Tsang MB, Lavi S, Cantor WJ, Madan M, Liu YY, Jolly SS. Association of Thrombus Aspiration With Time and Mortality Among Patients With ST-Segment Elevation Myocardial Infarction: A Post Hoc Analysis of the Randomized TOTAL Trial. JAMA Netw Open. 2021 Mar 1;4(3):e213505. doi: 10.1001/jamanetworkopen.2021.3505.
citation: Jolly SS, Cairns JA, Lavi S, Cantor WJ, Bernat I, Cheema AN, Moreno R, Kedev S, Stankovic G, Rao SV, Meeks B, Chowdhary S, Gao P, Sibbald M, Velianou JL, Mehta SR, Tsang M, Sheth T, Dzavik V; TOTAL Investigators. Thrombus Aspiration in Patients With High Thrombus Burden in the TOTAL Trial. J Am Coll Cardiol. 2018 Oct 2;72(14):1589-1596. doi: 10.1016/j.jacc.2018.07.047.
citation: Sheth TN, Kajander OA, Lavi S, Bhindi R, Cantor WJ, Cheema AN, Stankovic G, Niemela K, Natarajan MK, Shestakovska O, Tittarelli R, Meeks B, Jolly SS. Optical Coherence Tomography-Guided Percutaneous Coronary Intervention in ST-Segment-Elevation Myocardial Infarction: A Prospective Propensity-Matched Cohort of the Thrombectomy Versus Percutaneous Coronary Intervention Alone Trial. Circ Cardiovasc Interv. 2016 Apr;9(4):e003414. doi: 10.1161/CIRCINTERVENTIONS.115.003414.
citation: Jolly SS, Cairns JA, Yusuf S, Rokoss MJ, Gao P, Meeks B, Kedev S, Stankovic G, Moreno R, Gershlick A, Chowdhary S, Lavi S, Niemela K, Bernat I, Cantor WJ, Cheema AN, Steg PG, Welsh RC, Sheth T, Bertrand OF, Avezum A, Bhindi R, Natarajan MK, Horak D, Leung RC, Kassam S, Rao SV, El-Omar M, Mehta SR, Velianou JL, Pancholy S, Dzavik V; TOTAL Investigators. Outcomes after thrombus aspiration for ST elevation myocardial infarction: 1-year follow-up of the prospective randomised TOTAL trial. Lancet. 2016 Jan 9;387(10014):127-35. doi: 10.1016/S0140-6736(15)00448-1. Epub 2015 Oct 22.
citation: Jolly SS, Cairns JA, Yusuf S, Meeks B, Gao P, Hart RG, Kedev S, Stankovic G, Moreno R, Horak D, Kassam S, Rokoss MJ, Leung RC, El-Omar M, Romppanen HO, Alazzoni A, Alak A, Fung A, Alexopoulos D, Schwalm JD, Valettas N, Dzavik V; TOTAL Investigators. Stroke in the TOTAL trial: a randomized trial of routine thrombectomy vs. percutaneous coronary intervention alone in ST elevation myocardial infarction. Eur Heart J. 2015 Sep 14;36(35):2364-72. doi: 10.1093/eurheartj/ehv296. Epub 2015 Jun 29.
citation: Williams PD, Mamas MA, Fraser DG. A coronary artery cast. Can J Cardiol. 2011 Nov-Dec;27(6):871.e5-6. doi: 10.1016/j.cjca.2011.08.108. Epub 2011 Oct 14. No abstract available.