Find-A-Study

Optimal Delay Time to Initiate Anticoagulation After Ischemic Stroke in Atrial Fibrillation

Purpose

Title:

Optimal Delay Time to Initiate Anticoagulation after Ischemic Stroke in Atrial Fibrillation (START): a pragmatic, adaptive randomized clinical trial.

Primary Objective:

• To determine the optimal time to initiate anticoagulation with a Non-Vitamin K Oral Anticoagulant (NOAC) after ischemic stroke in patients with non-valvular atrial fibrillation.

Secondary Objectives:

To compare the rates of primary adverse outcomes in a per protocol analysis
To compare 30 day clinical outcomes by the modified Rankin scale among the time-to-treatment groups
To compare 30 day clinical outcomes by the PROMIS-10 scale among the time-to-treatment groups.
To compare 90 day clinical outcomes by the modified Rankin scale among the time-to-treatment groups
To explore the optimal timing in subgroups of age, sex, outcome category, and NOAC choice

Study Contact

Principal Investigator
Lee Birnbaum

Charlotte Rhodes
210-450-8454
rhodesc1@uthscsa.edu

Eligibility

Eligible Ages: Between N/A and N/A
Eligible Genders: All
Accepts Healthy Volunteers: No

Inclusion Criteria

New disabling neurological deficit attributable to new ischemic stroke.
Minimum lesion diameter of 1.5cm on qualifying imaging. If lesion not visible on imaging, NIHSS must be greater than 4.
Non-valvular atrial fibrillation (paroxysmal, persistent, or permanent).
Not currently anticoagulated and/or will not be anticoagulated prior to starting their NOAC at the randomized time of initiation (except for DVT prophylaxis).

Note: Patients who had been taking an anticoagulant prior to their qualifying index event (for any reason) are eligible for START, assuming the drug is no longer having a therapeutic effect in the patient's system by 48 hours from stroke onset.
Treating physician plans to anticoagulate with a FDA-approved novel oral anticoagulant (NOAC): apixaban, dabigatran, edoxaban, or rivaroxaban, or other FDA-approved NOAC.
Qualifying brain CT or MRI scan < 48hr from stroke onset (time last known well). If patient has been treated with thrombolytic or endovascular therapy for this stroke, then the qualifying scan is that which is performed after therapy to rule out clinically significant hemorrhagic transformation.
Ability to randomize within 60 hours of symptom onset.

Exclusion Criteria

Any clinical or imaging evidence of spontaneous intracranial hemorrhage in the previous 6 months.

Note: Patients with hemorrhagic transformation of current or previous ischemic stroke may be included per Investigator's judgment. Sporadic microbleeds may be included per Investigator's judgment. As a general recommendation, a cerebral microbleed is considered to be ≤ 5mm, but sometimes up to 10mm, in greatest diameter on gradient recalled echo (GRE), or T2*, MRI sequences. Any blood visualized on a CT will be classified as a macrobleed.
Infarct volume (estimated) is greater than 50% of middle cerebral artery territory on qualifying scan. If the full extent of the lesion is not visible, any patient with a NIHSS > 23 must be excluded.

Note: The lesion does not need to be restricted to the mCA, but if the lesion volume is estimated to be greater than half of the mCA territory, the patient should be excluded.

Note: In non-EVT patients, any NIHSS following the index stroke may be used to qualify the patient for START. For example, a patient that presents with a NIHSS of 10 who then receives tPA and improves to a NIHSS of 2 is still eligible for START. For patients whom had endovascular therapy, the qualifying NIHSS assessment is that which is obtained with their qualifying scan following therapy.
Anticipated need for major surgery over the next 30 days that would require delay, discontinuation, or extended suspension of anticoagulant of more than 5 days.
Symptomatic edema expected from size and location of ischemic stroke.
Decreased level of consciousness present or expected.
Life expectancy less than 90 days.
Follow-up in person or by telephone for 90 days is not feasible.

Study Design

Phase: Phase 3
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Prevention
Masking: Single (Outcomes Assessor)
Condition: Stroke

Arm Groups

Arm	Description	Intervention
Experimental 132 hours	Time to delay the initiation of anticoagulation is determined at randomization. The Time-To-Treatment Randomization of 60 hours correlates to starting treatment on Day 3, 132 hours starts on Day 6, 228 hours starts on Day 10, and 324 hours starts Day 14.	Other: Time-To-Treatment Randomization The time after symptom onset to initiate treatment will be randomized to one of four possible treatment arms: 60 hours, 132 hours, 228 hours, or 324 hours (+/- 12 hours each).
Experimental 324 hours	Time to delay the initiation of anticoagulation is determined at randomization. The Time-To-Treatment Randomization of 60 hours correlates to starting treatment on Day 3, 132 hours starts on Day 6, 228 hours starts on Day 10, and 324 hours starts Day 14.	Other: Time-To-Treatment Randomization The time after symptom onset to initiate treatment will be randomized to one of four possible treatment arms: 60 hours, 132 hours, 228 hours, or 324 hours (+/- 12 hours each).
Experimental 60 hours	Time to delay the initiation of anticoagulation is determined at randomization. The Time-To-Treatment Randomization of 60 hours correlates to starting treatment on Day 3, 132 hours starts on Day 6, 228 hours starts on Day 10, and 324 hours starts Day 14.	Other: Time-To-Treatment Randomization The time after symptom onset to initiate treatment will be randomized to one of four possible treatment arms: 60 hours, 132 hours, 228 hours, or 324 hours (+/- 12 hours each).
Experimental 228 hours	Time to delay the initiation of anticoagulation is determined at randomization. The Time-To-Treatment Randomization of 60 hours correlates to starting treatment on Day 3, 132 hours starts on Day 6, 228 hours starts on Day 10, and 324 hours starts Day 14.	Other: Time-To-Treatment Randomization The time after symptom onset to initiate treatment will be randomized to one of four possible treatment arms: 60 hours, 132 hours, 228 hours, or 324 hours (+/- 12 hours each).