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

NCT03759938 | Active Not Recruiting DMC

• 1 other identifier: 18/0316
• Study Type: interventional
• Target: 3,648
• Locations: 1 country
• Sites: 44

Brief 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). 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.

Conditions

Stroke, Acute; Atrial Fibrillation

Keywords

ischaemic stroke, atrial fibrilation

Outcome Measures

Primary Outcomes (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.

  At 90 days from randomisation

Secondary Outcomes (17)

• All-cause mortality

  At 90 days from randomisation

• Incidence of vascular death

  At 90 days from randomisation

• Incidence of recurrent ischaemic stroke

  At 90 days from randomisation

• Incidence of systemic embolism

  At 90 days from randomisation

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

  At 90 days from randomisation

Other Outcomes (2)

• Ongoing anticoagulation at 90 days

  At 90 days from randomisation

• Individual cognitive domain subscores

  At 90 days from randomisation

Study Arms (2)

Early initiation of DOAC

EXPERIMENTAL

Early 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

Drug: Direct oral anticoagulant (DOAC)

Standard Initiation of DOAC

ACTIVE COMPARATOR

Standard 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).

Drug: Direct oral anticoagulant (DOAC)

Interventions

Direct oral anticoagulant (DOAC) DRUG

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.

Also known as: dabigatran, apixaban, edoxaban, rivaroxaban

Early initiation of DOAC; Standard Initiation of DOAC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 years or over
• Clinical diagnosis of acute ischaemic stroke
• AF, confirmed by any of:
• lead ECG recording
• Inpatient ECG telemetry
• Other prolonged ECG monitoring technique (e.g. Holter monitor)
• 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.

You may not qualify if:

• 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)
• 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:

Sponsors & Collaborators

• University College, London: lead

Study Sites (44)

Bronglais General Hospital, Hywel Dda University Health Board

Aberystwyth, SY23 1ER, United Kingdom

Location

Royal United Hospitals Bath NHS Foundation Trust

Bath, BA1 3NG, United Kingdom

Location

Queen Elizabeth Hospital,University Hospitals Birmingham NHS Foundation

Birmingham, B15 2TH, United Kingdom

Location

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

Bournemouth, BH7 7DW, United Kingdom

Location

Bradford Royal Infirmary, Bradford Teaching Hospitals NHS Foundation Trust

Bradford, BD9 6RJ, United Kingdom

Location

Broomfield Hospital, Mid Essex Hospital Services NHS Trust

Broomfield, CM1 7ET, United Kingdom

Location

West Suffolk Hospital, West Suffolk NHS Foundation Trust

Bury St Edmunds, IP33 2QZ, United Kingdom

Location

Addenbrooke's Hospital NHS Trust

Cambridge, CB2 0QQ, United Kingdom

Location

Glangwili General Hospita, Hywel Dda University Health Boardl

Carmarthen, SA31 2AF, United Kingdom

Location

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

Chertsey, KT16 0PZ, United Kingdom

Location

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

Derby, DE22 3NE, United Kingdom

Location

Royal Devon & Exeter NHS Foundation Trust

Exeter, EX2 5DW, United Kingdom

Location

Withybush General Hospital, Hywel Dda University Health Board

Haverfordwest, SA61 2PZ, United Kingdom

Location

Wycombe Hospital, Buckinghamshire Healthcare NHS Trust

High Wycombe, HP11 2TT, United Kingdom

Location

Queen Elizabeth Hospital Kings Lynn NHS Trust

Kings Lynn, PE30 4ET, United Kingdom

Location

Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust

Leicester, LE1 5WW, United Kingdom

Location

Royal Liverpool and Broadgreen University Hospitals NHS Trust

Liverpool, L7 8XP, United Kingdom

Location

Prince Philip Hospital, Hywel Dda University Health Board

Llanelli, SA14 8QF, United Kingdom

Location

The Royal London Hospital, Barts Health NHS Trust

London, E1 1FR, United Kingdom

Location

Northwick Park Hospital, London North West Healthcare NHS Trust

London, HA1 3UJ, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, NW1 2BU, United Kingdom

Location

St George's University Hospitals NHS Foundation Trust

London, SW17 0QT, United Kingdom

Location

Charing Cross Hospital, Imperial College Healthcare NHS Trust

London, W6 8RF, United Kingdom

Location

Luton and Dunstable University Hospital NHS Foundation Trust

Luton, LU4 0DZ, United Kingdom

Location

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

Middlesbrough, TS4 3BW, United Kingdom

Location

Milton Keynes University Hospital NHS Foundation Trust

Milton Keynes, MK6 5LD, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, NG7 2UH, United Kingdom

Location

Derriford Hospital University Hospitals Plymouth NHS Trust

Plymouth, PL6 8DH, United Kingdom

Location

Poole Hospital NHS Foundation Trust

Poole, BH15 2JB, United Kingdom

Location

Royal Preston Hospital, Lancashire Teaching Hospitals

Preston, PR2 9HT, United Kingdom

Location

Royal Berkshire NHS Foundation Trust

Reading, RG1 5AN, United Kingdom

Location

Salford Royal Hospital, Salford Royal NHS Foundation Trust

Salford, M6 8HD, United Kingdom

Location

Salisbury District Hospital, Salisbury NHS Foundation Trust

Salisbury, SP2 8BJ, United Kingdom

Location

Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, S10 2JF, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust

Southampton, SO16 6YD, United Kingdom

Location

Southend University Hospital NHS Foundation Trust

Southend-on-Sea, SS0 0RY, United Kingdom

Location

Kings Mill Hospital, Sherwood Forest Hospitals NHS Foundation Trust

Sutton in Ashfield, NG17 4JL, United Kingdom

Location

Morriston Hospital, Swansea Bay University Health Board

Swansea, SA6 6NL, United Kingdom

Location

Torbay Hospital, Torbay and South Devon NHS Foundation

Torquay, TQ2 7AA, United Kingdom

Location

Arrowe Park Hospital, Wirral University Teaching Hospital NHS Foundation Trust

Upton, CH49 5PE, United Kingdom

Location

Watford General Hospital, West Hertfordshire Hospitals NHS Trust

Watford, WD18 0HB, United Kingdom

Location

Royal Hampshire County Hospital, Hampshire Hospitals NHS Foundation Trust

Winchester, SO22 5DG, United Kingdom

Location

Wrexham Maelor Hospital, Betsi Cadwaladr University Health Board

Wrexham, LL 13 7TD, United Kingdom

Location

York Teaching Hospital NHS Foundation Trust

York, YO31 8HE, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 40402086 DERIVED

• 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.

  PMID: 39966982 DERIVED

• 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.

  PMID: 39491870 DERIVED

• 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.

  PMID: 35018878 DERIVED

MeSH Terms

Conditions

Stroke; Atrial Fibrillation; Ischemic Stroke

Interventions

N(4)-oleylcytosine arabinoside; Dabigatran; apixaban; edoxaban; Rivaroxaban

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Heart Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines

Study Officials

• David Werring, Prof

  UCL

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The Event Adjudication Committee is a study group (of at least three members) responsible for the review of clinical events to ensure consistent, standardized, objective and unbiased results throughout all participating sites and minimise the likelihood of discrepant interpretations. This group consists of a panel of experts who have the relevant therapeutic area expertise, are experienced in clinical trials, and have been trained on the specific study protocol. The Event Adjudication Committee will centrally review events reported using all available clinical and imaging data and evaluate efficacy and/ or safety endpoints in a blinded and unbiased manner on a regular basis to ensure accurate, consistent and standardized assessments of important study events such as recurrent symptomatic ischaemic stroke, systemic embolism and death.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: November 27, 2018
• First Posted: November 30, 2018
• Study Start: June 18, 2019
• Primary Completion: May 30, 2024
• Study Completion: October 31, 2024
• Last Updated: May 14, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (44)