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Stroke, AcuteOPTIMASNCT03759938

OPTIMAS: OPtimal TIMing of Anticoagulation After Acute Ischaemic Stroke : a Randomised Controlled Trial

A study testing Direct oral anticoagulant (DOAC) in people with Stroke, Acute and Atrial Fibrillation, run by University College, London at 44 sites in United Kingdom.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

OPTIMAS is a large, prospective, partially blinded randomised controlled trial of early (within ≤4 days [96hrs]) or standard (between day 7 and day 14 after stroke onset) initiation of anticoagulation after stroke in patients with atrial fibrillation (AF), using any licensed dose of a direct oral anticoagulant (DOAC). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Stroke, Acute, Atrial Fibrillation
What is being tested?
Direct oral anticoagulant (DOAC)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3,648 participants
Where
44 sitesUnited Kingdom
Study dates
18 Jun 2019to 31 Oct 2024
Phase
Interventional
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Aged 18 years or over
  • Clinical diagnosis of acute ischaemic stroke
  • AF, confirmed by any of:
  • 12-lead ECG recording
  • Inpatient ECG telemetry
  • Other prolonged ECG monitoring technique (e.g. Holter monitor)
Show all 9Show fewer
  • Known diagnosis of atrial fibrillation verified by medical records (e.g. primary care records, letter from secondary care)
  • Eligibility to commence DOAC in accordance with approved prescribing recommendations confirmed by treating physician
  • Uncertainty on the part of the treating physician regarding early versus standard initiation of DOAC.

Who cannot join

  • Contraindication to anticoagulation:
  • Coagulopathy or current or recent anticoagulation with vitamin K antagonist (VKA) leading to INR ≥1.7 at randomisation.
  • Thrombocytopenia (platelets < 75 x 10⁹/L)
  • Other coagulopathy or bleeding tendency (based on clinical history or laboratory parameters) judged to contraindicate anticoagulation by treating clinician
  • Contraindication to early anticoagulation
  • Known presence of haemorrhagic transformation with parenchymal haematoma occupying >30% of the infarct volume and exerting significant mass effect (i.e. PH2) (NB: HI1, HI2 and PH1 are not considered contraindications)
Show all 25Show fewer
  • Presence of clinically significant intracranial haemorrhage unrelated to qualifying infarct
  • Any other contraindication to early anticoagulation as judged by the treating clinician
  • Contraindication to use of DOAC:
  • Known allergy or intolerance to both Factor Xa inhibitor and direct thrombin inhibitor
  • Definite indication for VKA treatment e.g. mechanical heart valve, valvular AF, antiphospholipid syndrome
  • Severe renal impairment with creatinine clearance (Cockcroft \& Gault formula) <15 mL/min (i.e. 14 mL/min or less)
  • Liver function tests ALT > 2x ULN
  • Cirrhotic patients with Child Pugh score equating to grade B or C
  • Patient is taking medication with significant interaction with DOAC, including:
  • Azole antifungals (e.g. ketoconazole, itraconazole)
  • HIV protease inhibitors (e.g. ritonavir)
  • Strong CYP3A4 inducers (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital or St. John's Wort)
  • Dronedarone
  • Pregnant or breastfeeding women
  • Presence on acute brain imaging of non-stroke pathology judged likely to explain clinical presentation (e.g. mass lesion, encephalitis)
  • Inability for patient to be followed up within 90 days of trial entry
  • Patient or representative refusal to consent to study procedures, including the site informing GP and healthcare professional responsible for anticoagulation care of participants
  • Any other reason that the PI considers would make the patient unsuitable to enter OPTIMAS.
  • Note that current DOAC treatment is NOT an exclusion criterion, as long as the treating physician considers it appropriate to restart (or continue) according to the timings specified in the OPTIMAS trial protocol. Continuation of the DOAC would be recorded as a start time of zero hours.

Trial locations and contacts

44 sites in 1 country.

44 sites in 1 country

United Kingdom44 sites

  • Bronglais General Hospital, Hywel Dda University Health Board

    Aberystwyth, SY23 1ER

  • Royal United Hospitals Bath NHS Foundation Trust

    Bath, BA1 3NG

  • Queen Elizabeth Hospital,University Hospitals Birmingham NHS Foundation

    Birmingham, B15 2TH

  • Royal Bournemouth Hospital, Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust

    Bournemouth, BH7 7DW

  • Bradford Royal Infirmary, Bradford Teaching Hospitals NHS Foundation Trust

    Bradford, BD9 6RJ

  • Broomfield Hospital, Mid Essex Hospital Services NHS Trust

    Broomfield, CM1 7ET

  • West Suffolk Hospital, West Suffolk NHS Foundation Trust

    Bury St Edmunds, IP33 2QZ

  • Addenbrooke's Hospital NHS Trust

    Cambridge, CB2 0QQ

  • Glangwili General Hospita, Hywel Dda University Health Boardl

    Carmarthen, SA31 2AF

  • St Peter's Hospital, Ashford and St. Peter's Hospitals NHS Foundation Trust

    Chertsey, KT16 0PZ

  • Royal Derby Hospital, University Hospitals of Derby and Burton NHS Foundation Trust

    Derby, DE22 3NE

  • Royal Devon & Exeter NHS Foundation Trust

    Exeter, EX2 5DW

  • Withybush General Hospital, Hywel Dda University Health Board

    Haverfordwest, SA61 2PZ

  • Wycombe Hospital, Buckinghamshire Healthcare NHS Trust

    High Wycombe, HP11 2TT

  • Queen Elizabeth Hospital Kings Lynn NHS Trust

    Kings Lynn, PE30 4ET

  • Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust

    Leicester, LE1 5WW

  • Royal Liverpool and Broadgreen University Hospitals NHS Trust

    Liverpool, L7 8XP

  • Prince Philip Hospital, Hywel Dda University Health Board

    Llanelli, SA14 8QF

  • The Royal London Hospital, Barts Health NHS Trust

    London, E1 1FR

  • Northwick Park Hospital, London North West Healthcare NHS Trust

    London, HA1 3UJ

  • University College London Hospitals NHS Foundation Trust

    London, NW1 2BU

  • St George's University Hospitals NHS Foundation Trust

    London, SW17 0QT

  • Charing Cross Hospital, Imperial College Healthcare NHS Trust

    London, W6 8RF

  • Luton and Dunstable University Hospital NHS Foundation Trust

    Luton, LU4 0DZ

  • The James Cook University Hospital, South Tees Hospitals NHS Foundation Trust

    Middlesbrough, TS4 3BW

  • Milton Keynes University Hospital NHS Foundation Trust

    Milton Keynes, MK6 5LD

  • Nottingham University Hospitals NHS Trust

    Nottingham, NG7 2UH

  • Derriford Hospital University Hospitals Plymouth NHS Trust

    Plymouth, PL6 8DH

  • Poole Hospital NHS Foundation Trust

    Poole, BH15 2JB

  • Royal Preston Hospital, Lancashire Teaching Hospitals

    Preston, PR2 9HT

  • Royal Berkshire NHS Foundation Trust

    Reading, RG1 5AN

  • Salford Royal Hospital, Salford Royal NHS Foundation Trust

    Salford, M6 8HD

  • Salisbury District Hospital, Salisbury NHS Foundation Trust

    Salisbury, SP2 8BJ

  • Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust

    Sheffield, S10 2JF

  • University Hospital Southampton NHS Foundation Trust

    Southampton, SO16 6YD

  • Southend University Hospital NHS Foundation Trust

    Southend-on-Sea, SS0 0RY

  • Kings Mill Hospital, Sherwood Forest Hospitals NHS Foundation Trust

    Sutton in Ashfield, NG17 4JL

  • Morriston Hospital, Swansea Bay University Health Board

    Swansea, SA6 6NL

  • Torbay Hospital, Torbay and South Devon NHS Foundation

    Torquay, TQ2 7AA

  • Arrowe Park Hospital, Wirral University Teaching Hospital NHS Foundation Trust

    Upton, CH49 5PE

  • Watford General Hospital, West Hertfordshire Hospitals NHS Trust

    Watford, WD18 0HB

  • Royal Hampshire County Hospital, Hampshire Hospitals NHS Foundation Trust

    Winchester, SO22 5DG

  • Wrexham Maelor Hospital, Betsi Cadwaladr University Health Board

    Wrexham, LL 13 7TD

  • York Teaching Hospital NHS Foundation Trust

    York, YO31 8HE

Other trials in United Kingdom

About this study

Official title: OPtimal TIMing of Anticoagulation After Acute Ischaemic Stroke: a Randomised Controlled Trial

OPTIMAS is a large, prospective, partially blinded randomised controlled trial of early (within ≤4 days [96hrs]) or standard (between day 7 and day 14 after stroke onset) initiation of anticoagulation after stroke in patients with atrial fibrillation (AF), using any licensed dose of a direct oral anticoagulant (DOAC). The trial will use a non-inferiority gatekeeper approach to test for non-inferiority of early anticoagulation followed by a test for superiority, if non-inferiority is established.

Read the detailed description

Current guidelines do not provide clear recommendations on the timing of OAC after acute AF-related stroke. Current United Kingdom (UK) guidelines for anticoagulation state that "delay for an arbitrary 2-week period is recommended" for "disabling" stroke and that anticoagulation can be started "no later than 14 days" for other strokes, at the prescriber's discretion.

OPTIMAS will investigate whether early initiation of DOAC treatment, within 4 days (96hrs) of onset, in patients with acute ischaemic stroke and AF is as effective as, or better than, standard initiation of DOAC treatment, no sooner than day 7 (>144hrs) and no later than day 14 (<336hrs) after onset, in preventing recurrent ischaemic stroke, systemic embolism and symptomatic intracranial haemorrhage (sICH)? Participants will be randomised 1:1 to the intervention or control. The exact timing of initiating treatment within each group is at the discretion of the treating clinician.

Being tested
Direct oral anticoagulant (DOAC)
Keywords
ischaemic stroke, atrial fibrilation
Medical subject headings
Stroke, Atrial Fibrillation, Ischemic Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Direct oral anticoagulant (DOAC)Drug

    Also called dabigatran, apixaban, edoxaban, rivaroxaban

    Any of the DOACs listed above may be used for treatment in either study arm. The DOAC will be supplied from normal hospital stock, using local hospital prescriptions.

Study groups in NCT03759938
Study groupRoleWhat they receive
Early initiation of DOACExperimentalEarly initiation of any direct oral anticoagulant (DOAC) at a dose licensed for stroke prevention in AF, within four days (96hrs) of onset of acute ischaemic stroke
Receives: Drug: Direct oral anticoagulant (DOAC)
Standard Initiation of DOACActive comparatorStandard initiation of any DOAC at a dose licensed for stroke prevention in AF, no sooner than day 7 and no later than day 14 after the onset of acute ischaemic stroke (i.e. between 144hrs and 336hrs from onset).
Receives: Drug: Direct oral anticoagulant (DOAC)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Composite outcome of the combined incidence of:recurrent symptomatic ischaemic stroke,symptomatic intracranial haemorrhage and systemic embolism

    OPTIMAS will investigate whether early initiation of DOAC treatment in patients with acute ischaemic stroke and atrial fibrillation is as effective as, or better than, standard initiation of DOAC treatment in preventing recurrent ischaemic stroke, systemic embolism and sICH.

    Measured: At 90 days from randomisation

Secondary outcomes (17)

  1. All-cause mortality

    All cause mortality reported in both arms

    Measured: At 90 days from randomisation

  2. Incidence of vascular death

    Any incidence of vascular death reported in both arms

    Measured: At 90 days from randomisation

  3. Incidence of recurrent ischaemic stroke

    Any incidence of recurrent ischaemic stroke reported in both arms

    Measured: At 90 days from randomisation

  4. Incidence of systemic embolism

    Any incidence of incidence of systemic embolism reported in both arms

    Measured: At 90 days from randomisation

  5. Incidence of venous thromboembolism (deep vein thrombosis [DVT], pulmonary embolism [PE], cerebral venous thrombosis [CVT])

    Any of Incidence of venous thromboembolism (deep vein thrombosis [DVT], pulmonary embolism [PE], cerebral venous thrombosis [CVT]) reported in both arms

    Measured: At 90 days from randomisation

  6. Functional status assessed by the modified Rankin scale (mRS) in both arms

    The Modified Rankin Scale measures the degree of disability and dependence following a stroke. The scale consists of 7 category descriptions, where 0 means no symptoms, 1 means no significant disability, 2 means slight disability, 3 means moderate disability, 4 means moderately severe disability, 5 means severe disability and 6 means death. The assessment is carried out by asking the participant or their carer about their activities of daily living.

    Measured: At 90 days from randomisation

  7. Cognitive ability assessed by the Montreal Cognitive Assessment (MoCA) questionnaire in both arms

    The Montreal Cognitive Assessment is a questionnaire widely used as a screening assessment for detecting cognitive impairment. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. An abbreviated version of the MoCA assessing attention, verbal learning, memory, executive functions/language and orientation can be performed over the phone. MoCA scores range between 0 and 30. A score of 26 or over is considered to be normal. In a study and people with mild cognitive impairment (MCI) scored an average of 22.1.

    Measured: At 90 days from randomisation

  8. Quality of life at 90 days assessed by EuroQol 5 Dimensions 5 level questionnaire [EQ-5D-5L] in both arms

    The EQ-5D-5L includes 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The EQ VAS records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. In instances in which the participant struggles with giving answers on their own, the participant's next-of-kin or a friend who knows the participant well will be asked to complete the EQ-5D-5L proxy version. The proxy is asked to rate how they think the participant would rate their own health-related quality of life, if the participant were able to communicate it. In case a proxy is not available, the research team member who was looking after the participant will complete it on their behalf.

    Measured: At 90 days from randomisation

  9. Patient reported outcomes assessed by the Patient-Reported Outcomes Measurement Information System Global Health questionnaire (PROMIS-10) in both arms.

    The PROMIS Global-10 short form consists of 10 items that assess general domains of health and functioning including overall physical health, mental health, social health, pain, fatigue, and overall perceived quality of life. The scoring system of the PROMIS Global-10 allows each of the individual items to be examined separately to provide specific information about perceptions of physical function, pain, fatigue, emotional distress, social health and general perceptions of health where 0 means never experienced this problem or symptoms and 1 means always. The higher score for each response indicate better health.

    Measured: At 90 days from randomisation

  10. Ongoing anticoagulation

    Ongoing anticoagulation will be assessed based on patient self-reporting and follow up patient medical records if necessary in both arms

    Measured: At 90 days from randomisation

  11. Time to first incidence of primary outcome component (recurrent ischaemic stroke, systemic embolism, or sICH)

    Time to first incidence of primary outcome component (recurrent ischaemic stroke, systemic embolism, or sICH) reported in both arms

    Measured: At 90 days from randomisation

  12. Length of hospital stay for stroke-related care

    Length of hospital stay for stroke-related care in both arms

    Measured: At 90 days from randomisation

  13. Health and social care resource use

    Health and social care resources (assessed by a study specific questionnaire) in both arms

    Measured: At 90 days from randomisation

  14. Incidence of symptomatic intracranial haemorrhage (sICH)

    Incidence of symptomatic intracranial haemorrhage (sICH) classified according to site intracerebral haemorrhage (within the brain parenchyma); subdural haemorrhage; extradural haemorrhage; subarachnoid haemorrhage; and haemorrhagic transformation of a brain infarct, in both arms

    Measured: At 90 days from randomisation

  15. Incidence of major extracranial bleeding

    Incidence of major extracranial bleeding reported in both arms

    Measured: At 90 days from randomisation

  16. Incidence of all major bleeding (intracranial and extracranial)

    Incidence of all major bleeding (intracranial and extracranial) reported during the study period, in both arms

    Measured: At 90 days from randomisation

  17. Incidence of clinically relevant non-major bleeding

    Incidence of clinically relevant non-major bleeding reported in both arms

    Measured: At 90 days from randomisation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Nov 2018
  2. Study start18 Jun 2019
  3. Primary completion30 May 2024 (estimated)
  4. Study completion31 Oct 2024 (estimated)

Resources

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 N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Patients will be randomised in a 1:1 ratio to intervention or control arms of the study. Participants and their physicians will not be blinded to study arm allocation.The exact timing of anticoagulation within the period specified for the allocated study arm is at the discretion of the treating physician, as is the choice of DOAC. Apart from the timing of DOAC initiation, the DOAC should be prescribed in accordance with usual clinical practice
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
3,648 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03759938
Sponsor's protocol ID
18/0316
Acronym
OPTIMAS
Status last verified
May 2024
First submitted
27 Nov 2018
Last updated
14 May 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Lyon J, Nash PS, Ahmed N, Aram L, Balogun M, Bennett K, Best JG, Bordea E, Caverly E, Chau M, Cohen H, Cullen M, Dehbi HM, Dore CJ, Engelter ST, Fenner R, Ford GA, Gill A, Hunter R, James M, Jayanthi A, Massingham S, Murray ML, Mazurczak I, Ndoutoumou A, Norrving BG, Philip J, Sims H, Sprigg N, Vanniyasingam T, Freemantle N, Lip GYH, Werring DJ; OPTIMAS Investigators. Early Versus Delayed Anticoagulation in Acute Ischemic Stroke According to Atrial Fibrillation Subtype and Time of Diagnosis: Subgroup Analysis of the OPTIMAS Randomized Controlled Trial. Stroke. 2026 Jun;57(6):1513-1525. doi: 10.1161/STROKEAHA.125.055037. Epub 2026 Apr 1.

    PubMed 41919368

  • Nash PS, Dehbi HM, Ahmed N, Arram L, Best JG, Balogun M, Bennett K, Bordea E, Caverly E, Chau M, Cohen H, Cullen M, Dore CJ, Engelter ST, Fenner R, Ford GA, Gill A, Hunter R, James M, Jayanthi A, Lip GYH, Massingham S, Murray ML, Mazurczak I, Ndoutoumou A, Norrving B, Philip J, Sims H, Sprigg N, Vanniyasingam T, Freemantle N, Wheeler DC, Werring DJ; OPTIMAS Investigators. Anticoagulation Timing in Acute Stroke With Atrial Fibrillation According to Chronic Kidney Disease: The OPTIMAS Trial. Stroke. 2025 Aug;56(8):1970-1979. doi: 10.1161/STROKEAHA.125.051457. Epub 2025 May 22.

    PubMed 40402086

  • Ahmed N, Dehbi HM, Freemantle N, Best J, Nash PS, Ruffle JK, Doig D, Werring DJ. Optimal timing of anticoagulation after acute ischaemic stroke with atrial fibrillation (OPTIMAS): statistical analysis plan for a randomised controlled trial. Trials. 2025 Feb 19;26(1):58. doi: 10.1186/s13063-025-08761-6.

    PubMed 39966982

  • Werring DJ, Dehbi HM, Ahmed N, Arram L, Best JG, Balogun M, Bennett K, Bordea E, Caverly E, Chau M, Cohen H, Cullen M, Dore CJ, Engelter ST, Fenner R, Ford GA, Gill A, Hunter R, James M, Jayanthi A, Lip GYH, Massingham S, Murray ML, Mazurczak I, Nash PS, Ndoutoumou A, Norrving B, Sims H, Sprigg N, Vanniyasingam T, Freemantle N; OPTIMAS investigators. Optimal timing of anticoagulation after acute ischaemic stroke with atrial fibrillation (OPTIMAS): a multicentre, blinded-endpoint, phase 4, randomised controlled trial. Lancet. 2024 Oct 23:S0140-6736(24)02197-4. doi: 10.1016/S0140-6736(24)02197-4. Online ahead of print.

    PubMed 39491870

  • Best JG, Arram L, Ahmed N, Balogun M, Bennett K, Bordea E, Campos MG, Caverly E, Chau M, Cohen H, Dehbi HM, Dore CJ, Engelter ST, Fenner R, Freemantle N, Hunter R, James M, Lip GY, Murray ML, Norrving B, Sprigg N, Veltkamp R, Zaczyk I, Werring DJ; OPTIMAS investigators. Optimal timing of anticoagulation after acute ischemic stroke with atrial fibrillation (OPTIMAS): Protocol for a randomized controlled trial. Int J Stroke. 2022 Jun;17(5):583-589. doi: 10.1177/17474930211057722. Epub 2022 Jan 12.

    PubMed 35018878

Questions about this trial

What is this clinical trial studying?

A study testing Direct oral anticoagulant (DOAC) in people with Stroke, Acute and Atrial Fibrillation, run by University College, London at 44 sites in United Kingdom.

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 9 inclusion and 25 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 14 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 44 sites in United Kingdom. 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.

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?

Composite outcome of the combined incidence of:recurrent symptomatic ischaemic stroke,symptomatic intracranial haemorrhage and systemic embolism (time frame: At 90 days from randomisation). 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 NCT03759938, which also lists 5 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 14 May 2024.

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