StrokePhase 3STARTNCT03021928
Optimal Delay Time to Initiate Anticoagulation After Ischemic Stroke in Atrial Fibrillation
A Phase 3 study testing Time-To-Treatment Randomization in people with Stroke, run by University of Texas at Austin at 15 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Stroke
- What is being tested?
- Time-To-Treatment Randomization
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 15 sitesUnited States
- Study dates
- 14 Jun 2017to Dec 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 10Show fewer
- 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.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
Dell Seton Medical Center at The University of Texas
Austin, Texas, 78701
Seton Medical Center Austin
Austin, Texas, 78705
St. David's Medical Center
Austin, Texas, 78705
CHI St. Joseph Health Regional Hospital
Bryan, Texas, 77802
Texas Health Presbyterian Hospital
Dallas, Texas, 75231
Parkland Memorial Hospital
Dallas, Texas, 75235
Baylor University Medical Center
Dallas, Texas, 75246
UT Southwestern William P. Clements Hospital
Dallas, Texas, 75390
UT Southwestern Zale Lipshy University Hospital
Dallas, Texas, 75390
Texas Tech University Health Science Center - El Paso University Medical Center
El Paso, Texas, 79905
Texas Health Harris Methodist Hospital
Fort Worth, Texas, 76104
The University of Texas Health Science Center at Houston
Houston, Texas, 77030
Seton Medical Center Hays
Kyle, Texas, 78640
Seton Medical Center Williamson
Round Rock, Texas, 78665
The University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
About this study
Title:
Optimal Delay Time to Initiate Anticoagulation after Ischemic Stroke in Atrial Fibrillation (START): a pragmatic, adaptive randomized clinical trial.
Read more
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 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
Read the detailed description
Long-term oral anticoagulation is standard for secondary stroke prevention in patients with atrial fibrillation (AFib). However, there is limited data and no consensus on the timing of when to initiate anticoagulation therapy, and concern that starting too soon risks symptomatic hemorrhagic transformation. These data are derived almost exclusively from heparins and Vitamin K antagonists (e.g.,warfarin). Now that NOACs have become the mainstay of stroke prophylaxis in AFib and have more rapid and consistent anticoagulation and fewer strokes (hemorrhagic especially), the question of optimal timing of NOAC initiation is of increasing importance.
The primary aim is to determine the time-to-treatment interval with the lowest associated risk for adverse events in the context of anticoagulation therapy with NOACs for acute stroke patients with non-valvular AFib. The question will be investigated with a prospective, adaptive, randomized, controlled "dose-exploration" trial with the time to treatment with NOAC therapy treated as the incremental "dose".
An adaptive, pragmatic trial will be performed that will not deviate from the treating physicians' usual practice except for randomizing the time to start the NOAC. Data collection will be limited to those fields necessary for the planned primary and secondary analyses.
The composite primary outcome event will be any of the following within 30 days of the index stroke: Ischemic Events (symptomatic ischemic stroke or systemic embolism) or Hemorrhagic Events (symptomatic hemorrhagic transformation of index ischemic stroke, other symptomatic intracranial hemorrhage, or major extracranial hemorrhage).
Four time-to-treatment intervals, i.e. study arms, between 2 and 14 days will be investigated: 72 (+/- 24) hours, 132 (+/- 12) hours, 228 (+/- 12) hours, and 324 (+/- 12) hours. An innovative adaptive design will be used which includes response adaptive randomization and modeling of ischemic and hemorrhagic outcome events. The ischemic and hemorrhagic events within the composite primary endpoint are modeled separately using their known monotonic property that the risk of an event increases (ischemic) or decreases (hemorrhage) as the time-to-treatment interval lengthens. Interim analysis will occur after 100 subjects are randomized and have the primary outcome, where the primary outcome will be analyzed and new randomization probabilities will be calculated to favor the arms that have a better risk-profile. Thereafter, interim analyses will occur after 50 subjects are randomized under the new randomization probabilities, and further new randomization probabilities will be calculated to favor the arms that have a better risk-profile.
- Conditions
- Stroke
- Being tested
- Time-To-Treatment Randomization
- Keywords
- Stroke, Atrial Fibrillation, Anticoagulation, NOAC
- Medical subject headings
- Stroke, Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Time-To-Treatment RandomizationOther
The time after symptom onset to initiate treatment will be randomized to one of four possible treatment arms: 72 (+/- 24) hours, 132 (+/- 12) hours, 228 (+/- 12) hours, and 324 (+/- 12) hours.
| Study group | Role | What they receive |
|---|---|---|
| 72 hours (Day 3-4) | Experimental | Time to delay the initiation of anticoagulation is determined at randomization. The Time-To-Treatment Randomization of 72 (+/-24) hours correlates to starting treatment on Day 3-4. Receives: Other: Time-To-Treatment Randomization |
| 132 hours (Day 6) | Experimental | Time to delay the initiation of anticoagulation is determined at randomization. The Time-To-Treatment Randomization of 132 (+/- 12) hours correlates to starting treatment on Day 6. Receives: Other: Time-To-Treatment Randomization |
| 228 hours (Day 10) | Experimental | Time to delay the initiation of anticoagulation is determined at randomization. The Time-To-Treatment Randomization of 228 (+/- 12) hours correlates to starting treatment on Day 10. Receives: Other: Time-To-Treatment Randomization |
| 324 hours Day 14. | Experimental | Time to delay the initiation of anticoagulation is determined at randomization. The Time-To-Treatment Randomization of 324 (+/- 12) hours starts Day 14. Receives: Other: Time-To-Treatment Randomization |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrent IschemicEvent
Any symptomatic ischemic stroke or systemic embolism as evidenced by either CT or MRI
Measured: 30 days
Hemorrhagic Event
Any symptomatic hemorrhagic transformation of index ischemic stroke, other symptomatic intracranial hemorrhage, or major extracranial hemorrhage as evidenced by CT or MRI
Measured: 30 days
Secondary outcomes (2)
Modified Rankin Scale
A modified Rankin scale (mRS) assessment will be performed by a qualified staff member.
Measured: 30 days
Modified Rankin Scale
A modified Rankin scale (mRS) assessment will be performed by a qualified staff member.
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2017 (estimated)
- Study start14 Jun 2017
- Primary completion3 Aug 2023
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by University of Texas at AustinThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas at Austin
- Sponsor type
- University, hospital or other
- Collaborators
- Lone Star Stroke Research Consortium, Texas Department of State Health Services
- Responsible party
- Principal investigator, Steven Warach, MD, PhD, University of Texas at Austin
- Investigators
- Steven Warach, MD, PhD, Principal investigator, University of Texas at AustinTruman J Milling, MD, Principal investigator, University of Texas at AustinPatrick Lawrence, BS, Study chair, University of Texas at Austin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03021928
- Sponsor's protocol ID
- 2017-09-0035
- Acronym
- START
- Status last verified
- Aug 2023
- First submitted
- 12 Jan 2017
- Last updated
- 8 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Jorgensen HS, Nakayama H, Reith J, Raaschou HO, Olsen TS. Acute stroke with atrial fibrillation. The Copenhagen Stroke Study. Stroke. 1996 Oct;27(10):1765-9. doi: 10.1161/01.str.27.10.1765.
PubMed 8841326Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD, Fang MC, Fisher M, Furie KL, Heck DV, Johnston SC, Kasner SE, Kittner SJ, Mitchell PH, Rich MW, Richardson D, Schwamm LH, Wilson JA; American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Council on Peripheral Vascular Disease. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014 Jul;45(7):2160-236. doi: 10.1161/STR.0000000000000024. Epub 2014 May 1.
PubMed 24788967The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group. Lancet. 1997 May 31;349(9065):1569-81.
PubMed 9174558Lee JH, Park KY, Shin JH, Cha JK, Kim HY, Kwon JH, Oh HG, Lee KB, Kim DE, Ha SW, Cho KH, Sohn SI, Oh MS, Yu KH, Lee BC, Kwon SU. Symptomatic hemorrhagic transformation and its predictors in acute ischemic stroke with atrial fibrillation. Eur Neurol. 2010;64(4):193-200. doi: 10.1159/000319048. Epub 2010 Aug 12.
PubMed 20714158January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy CW; ACC/AHA Task Force Members. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation. 2014 Dec 2;130(23):2071-104. doi: 10.1161/CIR.0000000000000040. Epub 2014 Mar 28. No abstract available.
PubMed 24682348Sandercock PA, Counsell C, Kane EJ. Anticoagulants for acute ischaemic stroke. Cochrane Database Syst Rev. 2015 Mar 12;2015(3):CD000024. doi: 10.1002/14651858.CD000024.pub4.
PubMed 25764172Kim TH, Kim JY, Mun HS, Lee HY, Roh YH, Uhm JS, Pak HN, Lee MH, Joung B. Heparin bridging in warfarin anticoagulation therapy initiation could increase bleeding in non-valvular atrial fibrillation patients: a multicenter propensity-matched analysis. J Thromb Haemost. 2015 Feb;13(2):182-90. doi: 10.1111/jth.12810. Epub 2015 Jan 7.
PubMed 25472735Diener HC, Connolly SJ, Ezekowitz MD, Wallentin L, Reilly PA, Yang S, Xavier D, Di Pasquale G, Yusuf S; RE-LY study group. Dabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischaemic attack or stroke: a subgroup analysis of the RE-LY trial. Lancet Neurol. 2010 Dec;9(12):1157-1163. doi: 10.1016/S1474-4422(10)70274-X. Epub 2010 Nov 6.
PubMed 21059484You JJ, Singer DE, Howard PA, Lane DA, Eckman MH, Fang MC, Hylek EM, Schulman S, Go AS, Hughes M, Spencer FA, Manning WJ, Halperin JL, Lip GYH. Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e531S-e575S. doi: 10.1378/chest.11-2304.
PubMed 22315271Connolly SJ, Milling TJ Jr, Eikelboom JW, Gibson CM, Curnutte JT, Gold A, Bronson MD, Lu G, Conley PB, Verhamme P, Schmidt J, Middeldorp S, Cohen AT, Beyer-Westendorf J, Albaladejo P, Lopez-Sendon J, Goodman S, Leeds J, Wiens BL, Siegal DM, Zotova E, Meeks B, Nakamya J, Lim WT, Crowther M; ANNEXA-4 Investigators. Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors. N Engl J Med. 2016 Sep 22;375(12):1131-41. doi: 10.1056/NEJMoa1607887. Epub 2016 Aug 30.
PubMed 27573206Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, Camm AJ, Weitz JI, Lewis BS, Parkhomenko A, Yamashita T, Antman EM. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014 Mar 15;383(9921):955-62. doi: 10.1016/S0140-6736(13)62343-0. Epub 2013 Dec 4.
PubMed 24315724Paciaroni M, Agnelli G, Falocci N, Caso V, Becattini C, Marcheselli S, Rueckert C, Pezzini A, Poli L, Padovani A, Csiba L, Szabo L, Sohn SI, Tassinari T, Abdul-Rahim AH, Michel P, Cordier M, Vanacker P, Remillard S, Alberti A, Venti M, Scoditti U, Denti L, Orlandi G, Chiti A, Gialdini G, Bovi P, Carletti M, Rigatelli A, Putaala J, Tatlisumak T, Masotti L, Lorenzini G, Tassi R, Guideri F, Martini G, Tsivgoulis G, Vadikolias K, Liantinioti C, Corea F, Del Sette M, Ageno W, De Lodovici ML, Bono G, Baldi A, D'Anna S, Sacco S, Carolei A, Tiseo C, Acciarresi M, D'Amore C, Imberti D, Zabzuni D, Doronin B, Volodina V, Consoli D, Galati F, Pieroni A, Toni D, Monaco S, Baronello MM, Barlinn K, Pallesen LP, Kepplinger J, Bodechtel U, Gerber J, Deleu D, Melikyan G, Ibrahim F, Akhtar N, Mosconi MG, Bubba V, Silvestri I, Lees KR. Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Effect of Anticoagulation and Its Timing: The RAF Study. Stroke. 2015 Aug;46(8):2175-82. doi: 10.1161/STROKEAHA.115.008891. Epub 2015 Jun 30.
PubMed 26130094Abdul-Rahim AH, Fulton RL, Frank B, Tatlisumak T, Paciaroni M, Caso V, Diener HC, Lees KR; VISTA collaborators. Association of improved outcome in acute ischaemic stroke patients with atrial fibrillation who receive early antithrombotic therapy: analysis from VISTA. Eur J Neurol. 2015 Jul;22(7):1048-55. doi: 10.1111/ene.12577. Epub 2014 Oct 16.
PubMed 25319957Shibazaki K, Kimura K, Aoki J, Saji N, Sakai K. Early initiation of new oral anticoagulants in acute stroke and TIA patients with nonvalvular atrial fibrillation. J Neurol Sci. 2013 Aug 15;331(1-2):90-3. doi: 10.1016/j.jns.2013.05.016. Epub 2013 Jun 3.
PubMed 23743245Bohmann F, Mirceska A, Pfeilschifter J, Lindhoff-Last E, Steinmetz H, Foerch C, Pfeilschifter W. No influence of dabigatran anticoagulation on hemorrhagic transformation in an experimental model of ischemic stroke. PLoS One. 2012;7(7):e40804. doi: 10.1371/journal.pone.0040804. Epub 2012 Jul 24.
PubMed 22911709
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimal Delay Time to Initiate Anticoagulation After Ischemic Stroke in Atrial Fibrillation
- ClinicalTrials.gov ID
- NCT03021928
- Acronym / sponsor ID
- START / 2017-09-0035
- Conditions
- Stroke
- Keywords
- Stroke, Atrial Fibrillation, Anticoagulation, NOAC
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (actual)
- Lead sponsor
- University of Texas at AustinUniversity, hospital or other
- Collaborators
- Lone Star Stroke Research Consortium, Texas Department of State Health Services
- Study start
- 14 Jun 2017 (actual)
- Primary completion
- 3 Aug 2023 (actual)
- Study completion
- Dec 2023 (estimated)
- First posted
- 16 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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
Detailed description
Long-term oral anticoagulation is standard for secondary stroke prevention in patients with atrial fibrillation (AFib). However, there is limited data and no consensus on the timing of when to initiate anticoagulation therapy, and concern that starting too soon risks symptomatic hemorrhagic transformation. These data are derived almost exclusively from heparins and Vitamin K antagonists (e.g.,warfarin). Now that NOACs have become the mainstay of stroke prophylaxis in AFib and have more rapid and consistent anticoagulation and fewer strokes (hemorrhagic especially), the question of optimal timing of NOAC initiation is of increasing importance.
The primary aim is to determine the time-to-treatment interval with the lowest associated risk for adverse events in the context of anticoagulation therapy with NOACs for acute stroke patients with non-valvular AFib. The question will be investigated with a prospective, adaptive, randomized, controlled "dose-exploration" trial with the time to treatment with NOAC therapy treated as the incremental "dose".
An adaptive, pragmatic trial will be performed that will not deviate from the treating physicians' usual practice except for randomizing the time to start the NOAC. Data collection will be limited to those fields necessary for the planned primary and secondary analyses.
The composite primary outcome event will be any of the following within 30 days of the index stroke: Ischemic Events (symptomatic ischemic stroke or systemic embolism) or Hemorrhagic Events (symptomatic hemorrhagic transformation of index ischemic stroke, other symptomatic intracranial hemorrhage, or major extracranial hemorrhage).
Four time-to-treatment intervals, i.e. study arms, between 2 and 14 days will be investigated: 72 (+/- 24) hours, 132 (+/- 12) hours, 228 (+/- 12) hours, and 324 (+/- 12) hours. An innovative adaptive design will be used which includes response adaptive randomization and modeling of ischemic and hemorrhagic outcome events. The ischemic and hemorrhagic events within the composite primary endpoint are modeled separately using their known monotonic property that the risk of an event increases (ischemic) or decreases (hemorrhage) as the time-to-treatment interval lengthens. Interim analysis will occur after 100 subjects are randomized and have the primary outcome, where the primary outcome will be analyzed and new randomization probabilities will be calculated to favor the arms that have a better risk-profile. Thereafter, interim analyses will occur after 50 subjects are randomized under the new randomization probabilities, and further new randomization probabilities will be calculated to favor the arms that have a better risk-profile.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 72 hours (Day 3-4) | Experimental | Other: Time-To-Treatment RandomizationTime to delay the initiation of anticoagulation is determined at randomization. The Time-To-Treatment Randomization of 72 (+/-24) hours correlates to starting treatment on Day 3-4. |
| 132 hours (Day 6) | Experimental | Other: Time-To-Treatment RandomizationTime to delay the initiation of anticoagulation is determined at randomization. The Time-To-Treatment Randomization of 132 (+/- 12) hours correlates to starting treatment on Day 6. |
| 228 hours (Day 10) | Experimental | Other: Time-To-Treatment RandomizationTime to delay the initiation of anticoagulation is determined at randomization. The Time-To-Treatment Randomization of 228 (+/- 12) hours correlates to starting treatment on Day 10. |
| 324 hours Day 14. | Experimental | Other: Time-To-Treatment RandomizationTime to delay the initiation of anticoagulation is determined at randomization. The Time-To-Treatment Randomization of 324 (+/- 12) hours starts Day 14. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Time-To-Treatment RandomizationThe time after symptom onset to initiate treatment will be randomized to one of four possible treatment arms: 72 (+/- 24) hours, 132 (+/- 12) hours, 228 (+/- 12) hours, and 324 (+/- 12) hours. | Other | 132 hours (Day 6), 228 hours (Day 10), 324 hours Day 14., 72 hours (Day 3-4) |
Primary outcome
Recurrent IschemicEvent
Time frame: 30 days
Any symptomatic ischemic stroke or systemic embolism as evidenced by either CT or MRI
Hemorrhagic Event
Time frame: 30 days
Any symptomatic hemorrhagic transformation of index ischemic stroke, other symptomatic intracranial hemorrhage, or major extracranial hemorrhage as evidenced by CT or MRI
2 secondary outcomes
Modified Rankin Scale
Time frame: 30 days
Modified Rankin Scale
Time frame: 90 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2023.
- Background: PubMed 8841326Jorgensen HS, Nakayama H, Reith J, Raaschou HO, Olsen TS. Acute stroke with atrial fibrillation. The Copenhagen Stroke Study. Stroke. 1996 Oct;27(10):1765-9. doi: 10.1161/01.str.27.10.1765.
- Background: PubMed 24788967Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD, Fang MC, Fisher M, Furie KL, Heck DV, Johnston SC, Kasner SE, Kittner SJ, Mitchell PH, Rich MW, Richardson D, Schwamm LH, Wilson JA; American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Council on Peripheral Vascular Disease. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014 Jul;45(7):2160-236. doi: 10.1161/STR.0000000000000024. Epub 2014 May 1.
- Background: PubMed 9174558The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group. Lancet. 1997 May 31;349(9065):1569-81.
- Background: PubMed 20714158Lee JH, Park KY, Shin JH, Cha JK, Kim HY, Kwon JH, Oh HG, Lee KB, Kim DE, Ha SW, Cho KH, Sohn SI, Oh MS, Yu KH, Lee BC, Kwon SU. Symptomatic hemorrhagic transformation and its predictors in acute ischemic stroke with atrial fibrillation. Eur Neurol. 2010;64(4):193-200. doi: 10.1159/000319048. Epub 2010 Aug 12.
- Background: PubMed 24682348January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy CW; ACC/AHA Task Force Members. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation. 2014 Dec 2;130(23):2071-104. doi: 10.1161/CIR.0000000000000040. Epub 2014 Mar 28. No abstract available.
- Background: PubMed 25764172Sandercock PA, Counsell C, Kane EJ. Anticoagulants for acute ischaemic stroke. Cochrane Database Syst Rev. 2015 Mar 12;2015(3):CD000024. doi: 10.1002/14651858.CD000024.pub4.
- Background: PubMed 25472735Kim TH, Kim JY, Mun HS, Lee HY, Roh YH, Uhm JS, Pak HN, Lee MH, Joung B. Heparin bridging in warfarin anticoagulation therapy initiation could increase bleeding in non-valvular atrial fibrillation patients: a multicenter propensity-matched analysis. J Thromb Haemost. 2015 Feb;13(2):182-90. doi: 10.1111/jth.12810. Epub 2015 Jan 7.
- Background: PubMed 21059484Diener HC, Connolly SJ, Ezekowitz MD, Wallentin L, Reilly PA, Yang S, Xavier D, Di Pasquale G, Yusuf S; RE-LY study group. Dabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischaemic attack or stroke: a subgroup analysis of the RE-LY trial. Lancet Neurol. 2010 Dec;9(12):1157-1163. doi: 10.1016/S1474-4422(10)70274-X. Epub 2010 Nov 6.
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- Website for the Lone Star Stroke ConsortiumLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven Warach, MD, PhD principal investigator
University of Texas at Austin
Truman J Milling, MD principal investigator
University of Texas at Austin
Patrick Lawrence, BS study chair
University of Texas at Austin
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Time-To-Treatment Randomization in people with Stroke, run by University of Texas at Austin at 15 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recurrent IschemicEvent (time frame: 30 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03021928, which also lists 16 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Aug 2023.