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

Sponsor

Population Health Research Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT03968393

Collaborator

Hamilton Health Sciences Corporation (Other)

2,800

Enrollment

Locations

Arms

89.6

Anticipated Duration (Months)

254.5

Patients Per Site

2.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Stroke Atrial Fibrillation	Drug: Investigators can choose from one of four Non-vitamin K oral anticoagulants (NOACs): Edoxaban 60mg daily, Apixaban 5mg twice daily, Dabigatran 110mg twice daily, or, Rivaroxaban 20mg daily.	Phase 4

Detailed Description

ASPIRE-AF is a prospective, randomized, open-label trial to assess the effects of non-vitamin K oral anticoagulants (NOACs) versus no anticoagulation in patients with transient perioperative atrial fibrillation after noncardiac surgery and additional stroke risk factors. The primary objective is to assess the effects of non-vitamin K oral anticoagulants (NOACs) versus no anticoagulation 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 Design

Study Type:

Interventional

Anticipated Enrollment :

2800 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Prospective, randomized, open-label clinical trial with blinded outcome assessmentProspective, randomized, open-label clinical trial with blinded outcome assessment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Jun 14, 2019

Anticipated Primary Completion Date :

Sep 1, 2026

Anticipated Study Completion Date :

Dec 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Non-vitamin K oral anticoagulant (NOAC) Patients allocated to the NOAC arm will receive oral anticoagulation for 24 months, unless the patient is discontinued for procedures with increased risk of bleeding, adverse events, low creatinine clearance, or patient decision.	Drug: Investigators can choose from one of four Non-vitamin K oral anticoagulants (NOACs): Edoxaban 60mg daily, Apixaban 5mg twice daily, Dabigatran 110mg twice daily, or, Rivaroxaban 20mg daily. Daily administration from time of randomization to final follow-up
No Intervention: No anticoagulation Patients allocated to the no anticoagulation arm are not allowed to receive oral anticoagulation, unless the patient develops an indication for its use during follow-up.

Arm

Intervention/Treatment

Experimental: Non-vitamin K oral anticoagulant (NOAC)

Patients allocated to the NOAC arm will receive oral anticoagulation for 24 months, unless the patient is discontinued for procedures with increased risk of bleeding, adverse events, low creatinine clearance, or patient decision.

Drug: Investigators can choose from one of four Non-vitamin K oral anticoagulants (NOACs): Edoxaban 60mg daily, Apixaban 5mg twice daily, Dabigatran 110mg twice daily, or, Rivaroxaban 20mg daily.

Daily administration from time of randomization to final follow-up

No Intervention: No anticoagulation

Patients allocated to the no anticoagulation arm are not allowed to receive oral anticoagulation, unless the patient develops an indication for its use during follow-up.

Outcome Measures

Primary Outcome Measures

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

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

Safety objective: incidence of composite of life-threatening, major, and critical organ bleeding [Up to 24 months, until final follow-up]
as previously used in the MANAGE trial
Safety objective: incidence of major bleeding [Up to 24 months, until final follow-up]
According to the ISTH criteria
Safety objective: incidence of hemorrhagic stroke [Up to 24 months, until final follow-up]
Tertiary objective: hospitalization for vascular causes [Up to 24 months, until final follow-up]
Tertiary objective: hospitalization for all causes [Up to 24 months, until final follow-up]

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

noncardiac surgery with at least an overnight hospital admission after surgery in the last 35 days;
≥1 episode of clinically important perioperative AF during or after their surgery;
sinus rhythm at the time of randomization; AND
any of the following high-risk criteria:
age 55-74 years, and having either known cardiovascular disease, recent major vascular surgery, or a CHA2DS2VASc score ≥3;OR
age ≥75 years.

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alberta Hospital	Edmonton	Alberta	Canada	T6G 2B7
2	Hamilton General Hospital	Hamilton	Ontario	Canada	L8L 2X2
3	St. Joseph's Healthcare Hamilton	Hamilton	Ontario	Canada	L8N 4A6
4	Juravinski Hospital	Hamilton	Ontario	Canada	L8V 1C3
5	Kingston General Hospital	Kingston	Ontario	Canada	K7L 2V7
6	University Hospital	London	Ontario	Canada	N6A 5A5
7	The Ottawa Hospital General Campus	Ottawa	Ontario	Canada	K1H 8L6
8	St. Catharines Site - Niagara Health System	St. Catharines	Ontario	Canada	L2S 0A9
9	Centre hospitalier de l'Université de Montréal	Montréal	Quebec	Canada	H2X 3E4
10	Halifax Infirmary	Halifax		Canada
11	Odense University Hospital	Odense		Denmark	5000

Sponsors and Collaborators

Population Health Research Institute
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