Early Versus Late Initiation of Anticoagulation in Mild-to-moderate AIS Patients With NVAF (ASAP)

Early Versus Late Initiation of Anticoagulation in Mild-to-moderate Acute Ischemic Stroke Patients With Non-valvular Atrial Fibrillation

The goal of this clinical trial is to compare the effectiveness between early and late initiation of anticoagulation therapy in acute ischemic stroke (AIS) patients with non-valvular atrial fibrillation (NVAF). Participants will be 1:1 randomized into early or late initiation group. The primary endpoint is early neurological deterioration (END) before discharge.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation; Acute Ischemic Stroke
• Intervention / Treatment: Drug: Anticoagulation Agents

Detailed Description

Anticoagulation therapy is effective to prevent ischemic stroke in patients with NVAF who have a history of stroke. Recent clinical trials have demonstrated that early initiation of anticoagulation therapy after AIS is safe, while no remarkable benefits have been observed. The goal of this clinical trial is to compare the effectiveness between early and late initiation of anticoagulation therapy in AIS patients with non-NVAF. Participants will be 1:1 randomized into early or late initiation group. The primary endpoint is END before discharge.

• Study Type: Interventional
• Enrollment (Estimated): 2351
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Min Lou, PhD; Phone Number: +8613958007213; Email: loumingxc@vip.sina.com

Study Locations

• China
  • Hangzhou, China
    • Recruiting
    • Second Affiliated Hospital, School of Medicine, Zhejiang University
    • Contact: Min Lou, PhD; Phone Number: 8657187784811; Email: loumingxc@vip.sina.com
  • Jiaxing, China
    • Recruiting
    • Jiaxing Second Hospital
    • Contact: Xiaoling Zhang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age > 18 years old
• Acute ischemic stroke with onset < 48 hours
• Have a history or newly diagnosed as NVAF
• NIHSS on admission <= 8

Exclusion Criteria:

• Chronic renal dysfunction (GFR < 30ml/min) or severe hepatic injury
• Have a history or newly diagnosed as valvular heart disease
• Mural thrombus in heart
• Contraindications of anticoagulation therapy within 12 days after AIS, e.g. severe intracranial hemorrhage
• Received reperfusion therapy, e.g. intravenous thrombolysis and endovascular treatment
• Concomitant stenosis (>50%) of carotid artery/intracranial artery, of which the ischemic lesion located within the territory
• Life expectancy less than 1 year
• Plan to receive invasive surgery in the following 3 months and have high risk of uncontrollable bleeding
• Pregnant or lactating women
• Individuals identified by researchers as unsuitable for participation in the study due to other reasons.

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: Early initiation of anticoagulation; For patients with NIHSS 0-3, anticoagulation therapy will be initiated within 0-3 days of onset. For patients with NIHSS 4-8, anticoagulation therapy will be initiated within 4-6 days of onset.	Drug: Anticoagulation Agents; Anticoagulation agents includes rivaroxaban, dabigatran, apixaban, and edoxaban.
Active Comparator: Late initiation of anticoagulation; For patients with NIHSS 0-3, anticoagulation therapy will be initiated within 4-12 days of onset. For patients with NIHSS 4-8, anticoagulation therapy will be initiated within 7-12 days of onset.	Drug: Anticoagulation Agents; Anticoagulation agents includes rivaroxaban, dabigatran, apixaban, and edoxaban.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early neurological deterioration before discharge	NIHSS at discharge increase at least 2 points compared with NIHSS on admission	At discharge, an average of 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
90-day ischemic stroke	Ischemic stroke within 90 days after enrollment	90 days
90-day hemorrhagic stroke	Hemorrhagic stroke within 90 days after enrollment	90 days
90-day myocardial infarction	Myocardial infarction within 90 days after enrollment	90 days
90-day major extracranial hemorrhage	Major extracranial hemorrhage within 90 days after enrollment	90 days
90-day non-major bleeding	Non-major bleeding within 90 days after enrollment	90 days
90-day vascular death	Vascular death within 90 days after enrollment	90 days
90-day all-cause death	All-cause death within 90 days after enrollment	90 days
90-day Composite events	Composite events including ischemic stroke, hemorrhagic stroke, myocardial infarction, systemic embolism, major extracranial hemorrhage, and vascular death within 90 days after enrollment	90 days
90-day systemic embolism	Systemic embolism within 90 days after enrollment	90 days
Discharge mRS	Modified Rankin scale at discharge	At discharge, an average of 7 days

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2023
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: September 13, 2023
• First Submitted That Met QC Criteria: September 21, 2023
• First Posted (Actual): September 28, 2023

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 15, 2024
• Last Verified: September 1, 2023

More Information

Terms related to this study

• 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; Ischemic Stroke; Atrial Fibrillation; Anticoagulants
• Other Study ID Numbers: ASAP

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