Anticoagulation for Stroke Prevention In Patients With Recent Episodes of Perioperative AF After Noncardiac Surgery (ASPIRE-AF)

Anticoagulation for Stroke Prevention In Patients With Recent Episodes of Perioperative Atrial Fibrillation After Noncardiac Surgery - The ASPIRE-AF Trial

Multinational, investigator-initiated study of oral anticoagulation versus no anticoagulation for the prevention of stroke and other adverse cardiovascular events in patients with transient perioperative atrial fibrillation after noncardiac surgery and additional stroke risk factors.

Study Overview

• Status: Recruiting
• Conditions: Stroke; Atrial Fibrillation
• Intervention / Treatment: Drug: Non-vitamin K oral anticoagulant (NOAC)

Detailed Description

ASPIRE-AF is a prospective, randomized, open-label trial of non-vitamin K oral anticoagulants (NOACs) versus no oral anticoagulation in patients with transient perioperative atrial fibrillation and additional stroke factors after noncardiac surgery. The primary objective is to assess the effects of NOACs on the co-primary composite outcomes of 1. non-hemorrhagic stroke and systemic embolism, and 2. vascular mortality, and non-fatal non-hemorrhagic stroke, myocardial infarction, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism 24 months after randomization.

• Study Type: Interventional
• Enrollment (Estimated): 2800
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Cassie McDonald; Phone Number: 1-905-594-0560; Email: aspireaf@phri.ca

Study Locations

• Argentina
  • Chivilcoy, Argentina, B6620
    • Not yet recruiting
    • Hospital Municipal Chivilcoy
    • Principal Investigator: Pablo Fernandez, MD
  • Santa Fe, Argentina, S2000GAP
    • Not yet recruiting
    • Hospital Privado de Rosario
    • Principal Investigator: Carlos Dumont, MD
  • Tucuman, Argentina, T4000
    • Not yet recruiting
    • Sanatorio Cisma
    • Principal Investigator: Guillermo Isa Messa, MD
  • Buenos Aires
    • Coronel Suárez, Buenos Aires, Argentina, 7540
      • Not yet recruiting
      • Clínica Coronel Suarez
      • Principal Investigator: Alberto Caccavo, MD
  • Santa Fe
    • Rosario, Santa Fe, Argentina, 2000
      • Not yet recruiting
      • Instituto de Investigaciones Clinicas Rosario
      • Principal Investigator: Mariela Rasmussen, MD
  • TDF
    • Ushuaia, TDF, Argentina, 9410
      • Not yet recruiting
      • Clinica San Jorge
      • Principal Investigator: Yamandu Leaden, MD
  • Tucuman
    • San Miguel De Tucumán, Tucuman, Argentina, 4000
      • Not yet recruiting
      • Centro Integral de Arritmias de Tucuman (CIAT)
      • Principal Investigator: Maria Cecilia Moris, MD
    • San Miguel De Tucumán, Tucuman, Argentina, 4000
      • Not yet recruiting
      • Sanatorio 9 de Julio
      • Principal Investigator: Mariano Estofan, MD
• Australia
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2605
      • Recruiting
      • Canberra Hospital
      • Principal Investigator: Walter Abhayaratna, MD
  • New South Wales
    • Bankstown, New South Wales, Australia, 2200
      • Not yet recruiting
      • Bankstown Hospital
      • Principal Investigator: Jens Killian, MD
    • Camperdown, New South Wales, Australia, 2050
      • Recruiting
      • Royal Prince Alfred Hospital
      • Principal Investigator: Sanjay Patel, MD
    • Concord, New South Wales, Australia, 2139
      • Recruiting
      • Concord Repatriation General Hospital
      • Principal Investigator: David Brieger, MD
    • Liverpool, New South Wales, Australia, 2170
      • Not yet recruiting
      • Liverpool Hospital
      • Principal Investigator: John French, MD
    • Newcastle, New South Wales, Australia, 2305
      • Recruiting
      • John Hunter Hospital
      • Principal Investigator: Aaron Sverdlov, MD
    • Westmead, New South Wales, Australia, 2145
      • Recruiting
      • Westmead Hospital
      • Principal Investigator: Clara Chow, MD
    • Wollongong, New South Wales, Australia, 2500
      • Not yet recruiting
      • Wollongong Hospital
      • Principal Investigator: Astin Lee, MD
  • Queensland
    • Birtinya, Queensland, Australia, 4575
      • Not yet recruiting
      • Sunshine Coast Hospital and Health Service
      • Principal Investigator: Nicholas New, MD
    • Brisbane, Queensland, Australia, 4064
      • Not yet recruiting
      • Wesley & Greenscopes Private Hospitals
      • Principal Investigator: David Colquhoun, MD
    • Herston, Queensland, Australia, 4029
      • Not yet recruiting
      • Royal Brisbane and Women's Hospital
      • Principal Investigator: John Atherton, MD
    • Redcliffe, Queensland, Australia, 4020
      • Recruiting
      • Redcliffe Hospital
      • Principal Investigator: Patrick Carroll, MD
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Not yet recruiting
      • Royal Adelaide Hospital
      • Principal Investigator: Peter Psaltis, MD
  • Victoria
    • Wangaratta, Victoria, Australia, 3677
      • Not yet recruiting
      • Northeast Health Wangaratta
      • Principal Investigator: Anthony Baird, MD
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Recruiting
      • Royal Perth Hospital
      • Principal Investigator: Graham Hillis, MD
• Brazil
  • Cerqueira César, Brazil, 05403-900
    • Not yet recruiting
    • Instituto do Coração do Hospital das Clínicas da FMUSP
    • Principal Investigator: Carlos Serrano, MD
  • Porto Alegre, Brazil, 90035-903
    • Recruiting
    • Hospital de Clinicas de Porto Alegre
    • Principal Investigator: Carisi Polanczyk, MD
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Not yet recruiting
      • Foothills Hospital
      • Principal Investigator: Shannon Ruzycki, MD
    • Edmonton, Alberta, Canada, T6G 2B7
      • Recruiting
      • University of Alberta Hospital
      • Principal Investigator: Finlay McAlister, MD
    • Medicine Hat, Alberta, Canada, T1A 4H6
      • Not yet recruiting
      • Medicine Hat Regional Hospital
      • Principal Investigator: Malay Shukla, MD
  • British Columbia
    • Cranbrook, British Columbia, Canada, V1C 3H9
      • Not yet recruiting
      • East Kootenay Regional Hospital
      • Principal Investigator: Denise Jaworsky, MD
    • Surrey, British Columbia, Canada, V3V 1Z2
      • Not yet recruiting
      • Fraser Health Authority
      • Principal Investigator: Mark Warwas, MD
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Recruiting
      • Health Sciences Centre Winnipeg
      • Principal Investigator: Sadeesh Srinathan, MD
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 2Z3
      • Not yet recruiting
      • Dr.-Georges-L.-Dumont University Hospital Centre
      • Principal Investigator: Remi LeBlanc, MD
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 3A6
      • Recruiting
      • Halifax Infirmary
      • Principal Investigator: Kim Styles, MD
    • Sydney, Nova Scotia, Canada, B1M 1A2
      • Not yet recruiting
      • Cape Breton University
      • Principal Investigator: Paul MacDonald, MD
  • Ontario
    • Cambridge, Ontario, Canada, N1R 6V6
      • Not yet recruiting
      • Cambridge Cardiac Care Centre
      • Principal Investigator: A. Shekhar Pandey, MD
    • Hamilton, Ontario, Canada, L8L 2X2
      • Recruiting
      • Hamilton General Hospital
      • Principal Investigator: Mohamed Panju, MD
    • Hamilton, Ontario, Canada, L8N 4A6
      • Recruiting
      • St. Joseph's Healthcare Hamilton
      • Principal Investigator: Vikas Tandon, MD
    • Hamilton, Ontario, Canada, L8V 1C3
      • Recruiting
      • Juravinski Hospital
      • Principal Investigator: Ameen Patel, MD
    • Kingston, Ontario, Canada, K7L 2V7
      • Recruiting
      • Kingston General Hospital
      • Principal Investigator: Michael McMullen, MD
    • London, Ontario, Canada, N6A 5A5
      • Recruiting
      • London Health Sciences Centre - University Hospital
      • Principal Investigator: Marko Mrkobrada, MD
    • Ottawa, Ontario, Canada, K1H 8L6
      • Recruiting
      • The Ottawa Hospital General Campus
      • Principal Investigator: James Villeneuve, MD
    • St. Catharines, Ontario, Canada, L2S 0A9
      • Recruiting
      • Niagara Health System - St. Catharine's Site
      • Principal Investigator: Leonard Blair, MD
  • Quebec
    • Montréal, Quebec, Canada, H2X 3E4
      • Recruiting
      • Centre Hospitalier de l'Université de Montréal
      • Principal Investigator: Isabelle Greiss, MD
    • Québec, Quebec, Canada, G1R 2J6
      • Not yet recruiting
      • Chu de Quebec Universite Laval
      • Principal Investigator: Sebastien Joncas, MD
    • Sherbrooke, Quebec, Canada, J1H 5H3
      • Recruiting
      • Hôpital Fleurimont du Centre hospitalier universitaire de Sherbrooke
      • Principal Investigator: Félix Ayala-Paredes, MD
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4P 0W5
      • Not yet recruiting
      • Regina General Hospital
      • Principal Investigator: Payam Dehghani, MD
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • Recruiting
      • Royal University Hospital
      • Principal Investigator: Michael Prystajecky, MD
• Denmark
  • Aarhus, Denmark, 8200
    • Not yet recruiting
    • Aarhus University Hospital
    • Principal Investigator: Erik Grove, MD
  • Esbjerg, Denmark, 6700
    • Recruiting
    • Hospital South West Jutland - University Hospital of Southern Denmark
    • Principal Investigator: Axel Brandes, MD
  • Odense, Denmark, 5000
    • Recruiting
    • Odense University Hospital
    • Principal Investigator: Axel Brandes, MD
• Germany
  • Leipzig, Germany, 04103
    • Not yet recruiting
    • Universitatsklinikum Leipzig
    • Principal Investigator: Rolf Wachter, MD
• India
  • Bangalore, India, 560034
    • Recruiting
    • St. John's Medical College Hospital
    • Principal Investigator: Joe Cherian, MD
  • Bengaluru, India, 560024
    • Not yet recruiting
    • Bangalore Baptist Hospital
    • Principal Investigator: Joel Jacob Chakravarthy, MD
  • Pondicherry, India, 605006
    • Not yet recruiting
    • JIPMER
    • Principal Investigator: Adinarayanan Sethurmachandran, MD
  • Pune, India, 411057
    • Not yet recruiting
    • Ruby Hall Clinic
    • Principal Investigator: Jagdish Hiremath, MD
  • Thiruvananthapuram, India, 695011
    • Not yet recruiting
    • Trivandrum Medical
    • Principal Investigator: Prem Menon, MD
  • Assam
    • North Guwāhāti, Assam, India, 781031
      • Not yet recruiting
      • GNRC Medical
      • Principal Investigator: Krishna Chaudra Narczarcy, MD
  • Gujarat
    • Ahmedabad, Gujarat, India, 380060
      • Not yet recruiting
      • Marengo CIMS Hospital
      • Principal Investigator: Ajay Naik, MD
  • Karnataka
    • Bangalore, Karnataka, India, 560010
      • Not yet recruiting
      • NU Hospitals
      • Principal Investigator: Pramod Krishnappa, MD
  • Kerala
    • Alappuzha, Kerala, India, 688005
      • Not yet recruiting
      • Govt. T.D. Medical College
      • Principal Investigator: Sajikumar Raghavan, MD
    • Thrissur, Kerala, India, 680555
      • Not yet recruiting
      • Amala Institute
      • Principal Investigator: Kishore Puthezhath, MD
• Italy
  • Alessandria, Italy, 15121
    • Not yet recruiting
    • Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo
    • Principal Investigator: Gabriele Colò, MD
  • Milan, Italy, 20122
    • Recruiting
    • Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico
    • Principal Investigator: Giuseppe Ristagno, MD
  • Palermo, Italy, 90146
    • Recruiting
    • La Maddalena
    • Principal Investigator: Salvatore D'Arpa, MD
  • Piacenza, Italy, 29121
    • Recruiting
    • Piacenza Ospedale
    • Contact: Maria Bolognesi, MD
  • Milan
    • Milano, Milan, Italy, 20162
      • Recruiting
      • ASST Grande Ospedale Metropolitano Niguarda
      • Principal Investigator: Matteo Baroni, MD
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Not yet recruiting
    • Seoul National University Hospital
    • Principal Investigator: Eue-Keun Choi, MD
  • Seoul, Korea, Republic of, 02841
    • Not yet recruiting
    • Korea University Ansm Hospital
    • Principal Investigator: Jong-Il Choi, MD
• Nepal
  • Lalitpur, Nepal, 44700
    • Recruiting
    • B and B Hospital
    • Principal Investigator: Rajib Rajbhandari, MD
• Netherlands
  • 's-Hertogenbosch, Netherlands, 5223
    • Recruiting
    • Jeroen Bosch Hospital
    • Principal Investigator: Jacob Van Eck, MD
  • Alkmaar, Netherlands, 1815
    • Recruiting
    • Noordwest Ziekenhuisgroep
    • Principal Investigator: Stefan Timmer, MD
  • Almelo, Netherlands, 7609
    • Recruiting
    • ZiekenhuisGroepTwente (ZGT)
    • Principal Investigator: Lambertus Pos, MD
  • Amstelveen, Netherlands, 1186
    • Recruiting
    • Ziekenhuis Amstelland
    • Principal Investigator: Freerk Broeyer, MD
  • Arnhem, Netherlands, 6815
    • Recruiting
    • Rijnstate Hospital
    • Principal Investigator: Ron Pisters, MD
  • Deventer, Netherlands, 7416
    • Recruiting
    • Deventer Ziekenhuis
    • Principal Investigator: Ype Tuininga, MD
  • Ede, Netherlands, 6716
    • Recruiting
    • Hospital Gelderse Vallei
    • Principal Investigator: Thomas Oosterhof, MD
  • Groningen, Netherlands, 9728
    • Recruiting
    • Martini Hospital
    • Principal Investigator: Robert Tieleman, MD
  • Rotterdam, Netherlands, 3083
    • Recruiting
    • Ikazia Hospital
    • Principal Investigator: Stieneke Zoet-Nugteren, MD
  • Rotterdam, Netherlands, 3045
    • Recruiting
    • Franciscus Gasthuis
    • Principal Investigator: Peter Nierop, MD
  • Tilburg, Netherlands, 5022
    • Recruiting
    • ETZ Tilburg
    • Principal Investigator: Walter Hermans, MD
• New Zealand
  • Dunedin, New Zealand, 9016
    • Not yet recruiting
    • Dunedin Public Hospital
    • Principal Investigator: James Pemberton, MD
  • Hamilton, New Zealand, 3204
    • Not yet recruiting
    • Waikato Hospital
    • Principal Investigator: Martin Stiles, MD
• Pakistan
  • Islamabad, Pakistan
    • Recruiting
    • Shifa International Hospital
    • Principal Investigator: Saeed Ullah Shah, MD
  • Karachi, Pakistan
    • Recruiting
    • Dow Medical University
    • Principal Investigator: Muhammad Tariq Farman, MD
  • Sindh
    • Karachi, Sindh, Pakistan, 74000
      • Recruiting
      • Aga Khan University
      • Principal Investigator: Yawer Saeed, MD
• Spain
  • Barcelona, Spain, 08025
    • Recruiting
    • Hospital de la Santa Creu i Sant Pau
    • Principal Investigator: Jose M Guerra, MD
  • Barcelona, Spain, 08003
    • Not yet recruiting
    • Hospital de Mar
    • Principal Investigator: Sandra Beltran de Heredia Marrodan, MD
  • Barcelona, Spain, 08014
    • Not yet recruiting
    • Vall d'Hebron Hospital
    • Principal Investigator: Montserrat Ribas Ball, MD
  • Madrid, Spain, 28034
    • Recruiting
    • University Hospital Ramon y Cajal
    • Principal Investigator: Jesus Alvarez Garcia, MD
• Sweden
  • Uppsala, Sweden, 751 85
    • Recruiting
    • Uppsala University
    • Principal Investigator: Claes Held, MD
    • Principal Investigator: Gorav Batra, MD
• Switzerland
  • Basel, Switzerland, 4031
    • Recruiting
    • University Hospital Basel
    • Principal Investigator: Philipp Krisai, MD
• United Kingdom
  • Liverpool, United Kingdom, L14 3PE
    • Recruiting
    • Liverpool Heart and Chest Hospital
    • Principal Investigator: Michael Shackcloth, MD
  • Lancashire
    • Blackpool, Lancashire, United Kingdom, FY3 8NR
      • Not yet recruiting
      • Blackpool Teaching Hospital
      • Principal Investigator: Alex Blackmore, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. noncardiac surgery with at least an overnight hospital admission after surgery in the last 35 days;
2. ≥1 episode of clinically important perioperative AF during or after their surgery;
3. sinus rhythm at the time of randomization; AND

4. any of the following high-risk criteria:

   1. age 55-74 years, and having either known cardiovascular disease, recent major vascular surgery, or a CHA2DS2VASc score ≥3;OR
   2. age ≥75 years.

Exclusion Criteria:

1. history of documented AF prior to noncardiac surgery;
2. need for long-term systemic anticoagulation;
3. ongoing need for long-term dual antiplatelet treatment;
4. contraindication to oral anticoagulation;
5. severe renal insufficiency (eGFR <30 ml/min);
6. acute stroke in the past 3 months;
7. underwent cardiac surgery in the past 3 months;
8. history of nontraumatic intracranial, intraocular, or spinal bleeding;
9. hemorrhagic disorder or bleeding diathesis;
10. expected to be non-compliant with follow-up and/or study medications;
11. known life expectancy less than 1 year due to concomitant disease;
12. women who are pregnant, breastfeeding, or of childbearing potential who are not taking effective contraception; OR
13. previously enrolled in the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Non-vitamin K oral anticoagulant (NOAC); Participants randomized to the intervention arm will be prescribed one of the following NOACs for 24 months, unless they are undergoing a procedure with an increased risk of bleeding, have an adverse event or low calculated creatinine clearance, or decide to discontinue their use.	Drug: Non-vitamin K oral anticoagulant (NOAC); Participants randomized to the intervention arm will be prescribed one of the following NOACs for 24 months: edoxaban 60 mg daily (dose reduction to 30 mg, if applicable), apixaban 5 mg twice daily (dose reduction to 2.5 mg, if applicable), dabigatran 110 mg twice daily, or rivaroxaban 20 mg daily (dose reduction to 15 mg, if applicable). The choice of NOAC will be left up to the participant's prescribing physician.; Other Names: Apixaban; Dabigatran; Edoxaban; Rivaroxaban
No Intervention: No anticoagulation; Participants randomized to the control arm will not be prescribed an oral anticoagulant unless they develop a clear indication for one during follow-up (e.g., recurrent nonoperative AF). They can be newly prescribed or continue taking low dose aspirin or another single antiplatelet agent as per the protocol. This will be decided by the participant's physician.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of Non-hemorrhagic stroke or systemic embolism	Up to 24 months, until final follow-up
Incidence of vascular mortality, and non-fatal non-hemorrhagic stroke, myocardial infarction, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism	Up to 24 months, until final follow-up

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of vascular mortality	Up to 24 months, until final follow-up
Incidence of non-fatal, non-hemorrhagic stroke	Up to 24 months, until final follow-up
Incidence of Myocardial infarction	Up to 24 months, until final follow-up
Incidence of peripheral arterial thrombosis	Up to 24 months, until final follow-up
Incidence of amputation	Up to 24 months, until final follow-up
Incidence of symptomatic venous thromboembolism	Up to 24 months, until final follow-up
Incidence of all-cause stroke	Up to 24 months, until final follow-up
Incidence of all-cause mortality	Up to 24 months, until final follow-up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of composite of life-threatening, major, and critical organ bleeding	Safety objective, measured as previously done in the MANAGE trial	Up to 24 months, until final follow-up
Incidence of major bleeding	Safety objective, measured according to the ISTH criteria	Up to 24 months, until final follow-up
Incidence of hemorrhagic stroke	Safety objective	Up to 24 months, until final follow-up
Hospitalization for vascular causes	Tertiary Objective	Up to 24 months, until final follow-up
Hospitalization for all causes	Tertiary Objective	Up to 24 months, until final follow-up

Collaborators and Investigators

• Sponsor: Population Health Research Institute
• Collaborators: Hamilton Health Sciences Corporation
• Investigators: Principal Investigator: David Conen, MD, MPH, Population Health Research Institute; Study Chair: PJ Devereaux, MD, PhD, Population Health Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2019
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: March 22, 2019
• First Submitted That Met QC Criteria: May 27, 2019
• First Posted (Actual): May 30, 2019

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Transient Atrial Fibrillation; Perioperative Atrial Fibrillation; Non-vitamin K Oral Anticoagulation; Noncardiac Surgery; PROBE Design
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arrhythmias, Cardiac; Stroke; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Rivaroxaban; Dabigatran; Apixaban; Edoxaban; Anticoagulants
• Other Study ID Numbers: 2019-ASPIREAF; 2019-001336-62 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No