| 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
|
|
|
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
|
|
|
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. |