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CTRI Number  CTRI/2023/01/049006 [Registered on: 13/01/2023] Trial Registered Prospectively
Last Modified On: 10/10/2024
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Process of Care Changes 
Study Design  Randomized, Parallel Group Trial 
Public Title of Study   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. 
Scientific Title of Study   Anticoagulation for Stroke Prevention In patients with Recent Episodes of perioperative Atrial Fibrillation after noncardiac surgery 
Trial Acronym  ASPIRE-AF 
Secondary IDs if Any  
Secondary ID  Identifier 
NCT03968393  ClinicalTrials.gov 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Prof Dr Alben Sigamani 
Designation  Director 
Affiliation  Carmel Research Consultancy Pvt Ltd 
Address  No 56 1st Cross Residency Layout
Opp Mayo Hall
Bangalore
KARNATAKA
560025
India 
Phone  8884431444  
Fax    
Email  dralbens@myrescon.com  
 
Details of Contact Person
Scientific Query
 
Name  Prof Dr Alben Sigamani 
Designation  Director 
Affiliation  Carmel Research Consultancy Pvt Ltd 
Address  No 56 1st Cross Residency Layout
Opp Mayo Hall
Bangalore
KARNATAKA
560025
India 
Phone  8884431444  
Fax    
Email  dralbens@myrescon.com  
 
Details of Contact Person
Public Query
 
Name  Prof Dr Alben Sigamani 
Designation  Director 
Affiliation  Carmel Research Consultancy Pvt Ltd 
Address  No 56 1st Cross Residency Layout
Opp Mayo Hall
Bangalore
KARNATAKA
560025
India 
Phone  8884431444  
Fax    
Email  dralbens@myrescon.com  
 
Source of Monetary or Material Support  
Population Health Research Institution Hamilton General Hospital Campus, 237 Barton Street East, Hamilton, Ontario Canada L8L 2X2 
 
Primary Sponsor  
Name  Population Health Research Institute 
Address  ASPIRE-AF Study Project Office Population Health Research Institute Hamilton General Hospital Campus, DBCVSRI 237 Barton Street East, Room C1-239 Hamilton, Ontario, Canada L8L 2X2 
Type of Sponsor  Research institution 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     Canada
Denmark
India
Nepal  
Sites of Study
Modification(s)  
No of Sites = 7  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Kishore Puthezhath  Amala Institute of Medical Sciences  Amala Institute of Medical Sciences, Amala Nagar PO, Thrissur-680555, Kerala
Thrissur
KERALA 
9349371606

drkmenon@gmail.com 
DrJagdish Hiremath  Grant Medical Foundation Ruby Hall Clinic  Department of Cardiology, 40,Sassoon Road, Pune,Maharashtra
Pune
MAHARASHTRA 
9822022441

drjagdishhiremath@gmail.com 
Dr Adinarayanan  Jawaharlal Institute of Postgraduate Medical Education & Research  Department of Anaesthesiology and Critical Care JIPMER, Dhanvantri Nagar, Gorimedu,Pondicherry 605006
Pondicherry
PONDICHERRY 
9442396762

adinarayanans@gmail.com 
Dr Pramod Krishnappa  NU Hospitals  NU Hospitals 4/1, West of Chord Road, Near ISKCON
Bangalore
KARNATAKA 
9886258999

dr.pramod@nuhospitals.com 
Dr Joe Joseph Cherian  St. John’s Medical College Hospital  Department of Orthopedics St. John’s Medical College Hospital Koramangala 560103
Bangalore
KARNATAKA 
9343794300

cherianjoe71@gmail.com 
Dr Sajikumar NR  TD Medical College  Govt. T.D. Medical College Vandanam, Alappuzha, Kerala, India
Alappuzha
KERALA 
00919995209868

drsajikumarnr@gmail.com 
Dr Prem Menon  Trivandrum Medical College  Division of Orthopaedic surgery and Traumatology Government Medical College, Trivandrum Ulloor - Akkulam Rd, near SAT hospital Medical College Junction, Chalakkuzhi, 695011
Thiruvananthapuram
KERALA 
9447399970

phmenon777@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 7  
Name of Committee  Approval Status 
Ethics Committee AIMS Thrissur  Approved 
Government Medical College Trivandrum Hospital Ethics Committee  Submittted/Under Review 
Institutional Ethics Committee, Jawaharlal Institute of Postgraduate Medical Education and Research  Approved 
Institutional Ethics Committee, Poona Medical Research Foundation   Approved 
Institutional Ethics Committee, St Johns Medical College and Hospital  Approved 
Instutional Ethics CommitteeGovernment T.D. Medical College, Vandanam  Approved 
NU Hospitals Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: I48||Atrial fibrillation and flutter, (2) ICD-10 Condition: I63||Cerebral infarction,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  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. 
Intervention  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. 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.  
 
Inclusion Criteria  
Age From  55.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  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:

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



 
 
ExclusionCriteria 
Details  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 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Outcome Assessor Blinded 
Primary Outcome  
Outcome  TimePoints 
1.Incidence of Non-hemorrhagic stroke or systemic embolism
2.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  
Outcome  TimePoints 
1.Incidence of vascular mortality
2.Incidence of non-fatal, non-hemorrhagic stroke
3.Incidence of Myocardial infarction
4.Incidence of peripheral arterial thrombosis
5.Incidence of amputation
6.Incidence of symptomatic venous thromboembolism
7.Incidence of all-cause stroke
8.Incidence of all-cause mortality
 
Up to 24 months, until final follow-up  
 
Target Sample Size   Total Sample Size="2800"
Sample Size from India="300" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 4 
Date of First Enrollment (India)   10/04/2023 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  14/06/2019 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="7"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)   Open to Recruitment 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details   NIL 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary  

Globally over 230 million major surgical procedures are undertaken every year . One of the most common cardiovascular complications in the perioperative period is atrial fibrillation (AF), with an overall incidence after noncardiac surgery of approximately 3% . This incidence can increase to up to 20% after high-risk surgeries, such as major thoracic surgery.

Non-operative AF is a major risk factor for the occurrence of death, stroke, congestive heart failure and cognitive dysfunction . The incidence of stroke in patients with non-operative AF and additional cardiovascular risk factors is ≥4.5 per 100 patient-years of follow-up . Oral anticoagulation with vitamin K antagonists in these patients reduces the relative risk of stroke by 64%  and is a Class I indication in Canadian and international guidelines . Compared to vitamin K antagonists, non-vitamin K oral anticoagulants (NOACs) are easier to use, safer, and at least as effective . Most guidelines now recommend NOACs as a first-line treatment in non-operative AF patients .

Much less is known about perioperative AF. While perioperative AF may be a time-limited phenomenon due to perioperative stress or inflammation, affected patients do have an increased risk of stroke and death in the first month after surgery . In the Perioperative Ischemic Evaluation-1 (POISE-1) trial, a large randomized controlled trial (RCT) of over 8,000 patients undergoing noncardiac surgery, patients who developed perioperative AF had a higher risk of stroke within 30 days after surgery . However, a minority of these patients received therapeutic dose anticoagulation, even when their “Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, previous Stroke/transient ischemic attack (doubled risk weight)” (CHADS2) score was high.

There are few published data on the long-term risk of stroke and other adverse outcomes in patients with perioperative AF . In an analysis from POISE-1 and POISE-2, patients with perioperative AF after noncardiac surgery were found to have an incidence of stroke at one year of 5.58 per 100 person-years of follow-up compared with 1.54 among patients without perioperative AF (adjusted hazard ratio [HR], 3.43; 95% CI, 2.00-5.90). Patients with perioperative AF also had an increased risk of all-cause mortality (incidence per 100 person-years 31.4 versus 9.3; adjusted HR 2.51; 95% CI, 2.01-3.14; p<0.001) .

These findings suggest patients with perioperative AF have a poor long-term prognosis and, given the benefits of oral anticoagulation in non-operative AF, that these medications may also be beneficial in patients with perioperative AF. There is, however, no high-quality evidence available to guide clinical practice. This is critical as it is unclear whether the stroke mechanisms are the same in patients with perioperative AF compared to patients with non-operative AF. Moreover, while postoperative patients have an increased risk of bleeding, oral anticoagulation may help prevent other thrombotic events and thus confer additional benefits . Therefore, the benefit-risk balance of anticoagulation in this patient population is unknown and requires further investigation. The current ASPIRE-AF trial will determine the efficacy and safety of oral anticoagulation in patients with perioperative AF after noncardiac surgery.

 
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