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

NCT ID: NCT03759938

Last Updated: 2024-05-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

3648 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-06-18

Study Completion Date

2024-10-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Stroke, Acute Atrial Fibrillation

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
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.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Early initiation of DOAC

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

Group Type EXPERIMENTAL

Direct oral anticoagulant (DOAC)

Intervention Type 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.

Standard Initiation of DOAC

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).

Group Type ACTIVE_COMPARATOR

Direct oral anticoagulant (DOAC)

Intervention Type 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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Direct oral anticoagulant (DOAC)

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.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

dabigatran, apixaban, edoxaban, rivaroxaban

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Aged 18 years or over
2. Clinical diagnosis of acute ischaemic stroke
3. AF, confirmed by any of:

1. 12-lead ECG recording
2. Inpatient ECG telemetry
3. Other prolonged ECG monitoring technique (e.g. Holter monitor)
4. Known diagnosis of atrial fibrillation verified by medical records (e.g. primary care records, letter from secondary care)
4. Eligibility to commence DOAC in accordance with approved prescribing recommendations confirmed by treating physician
5. Uncertainty on the part of the treating physician regarding early versus standard initiation of DOAC.

Exclusion Criteria

1. Contraindication to anticoagulation:

1. Coagulopathy or current or recent anticoagulation with vitamin K antagonist (VKA) leading to INR ≥1.7 at randomisation.
2. Thrombocytopenia (platelets \< 75 x 10⁹/L)
3. Other coagulopathy or bleeding tendency (based on clinical history or laboratory parameters) judged to contraindicate anticoagulation by treating clinician
2. Contraindication to early anticoagulation

1. 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)
2. Presence of clinically significant intracranial haemorrhage unrelated to qualifying infarct
3. Any other contraindication to early anticoagulation as judged by the treating clinician
3. Contraindication to use of DOAC:

1. Known allergy or intolerance to both Factor Xa inhibitor and direct thrombin inhibitor
2. Definite indication for VKA treatment e.g. mechanical heart valve, valvular AF, antiphospholipid syndrome
3. Severe renal impairment with creatinine clearance (Cockcroft \& Gault formula) \<15 mL/min (i.e. 14 mL/min or less)
4. Liver function tests ALT \> 2x ULN
5. Cirrhotic patients with Child Pugh score equating to grade B or C
6. 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
4. Pregnant or breastfeeding women
5. Presence on acute brain imaging of non-stroke pathology judged likely to explain clinical presentation (e.g. mass lesion, encephalitis)
6. Inability for patient to be followed up within 90 days of trial entry
7. Patient or representative refusal to consent to study procedures, including the site informing GP and healthcare professional responsible for anticoagulation care of participants
8. 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University College, London

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

David Werring, Prof

Role: STUDY_CHAIR

UCL

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Bronglais General Hospital, Hywel Dda University Health Board

Aberystwyth, , United Kingdom

Site Status

Royal United Hospitals Bath NHS Foundation Trust

Bath, , United Kingdom

Site Status

Queen Elizabeth Hospital,University Hospitals Birmingham NHS Foundation

Birmingham, , United Kingdom

Site Status

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

Bournemouth, , United Kingdom

Site Status

Bradford Royal Infirmary, Bradford Teaching Hospitals NHS Foundation Trust

Bradford, , United Kingdom

Site Status

Broomfield Hospital, Mid Essex Hospital Services NHS Trust

Broomfield, , United Kingdom

Site Status

West Suffolk Hospital, West Suffolk NHS Foundation Trust

Bury St Edmunds, , United Kingdom

Site Status

Addenbrooke's Hospital NHS Trust

Cambridge, , United Kingdom

Site Status

Glangwili General Hospita, Hywel Dda University Health Boardl

Carmarthen, , United Kingdom

Site Status

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

Chertsey, , United Kingdom

Site Status

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

Derby, , United Kingdom

Site Status

Royal Devon & Exeter NHS Foundation Trust

Exeter, , United Kingdom

Site Status

Withybush General Hospital, Hywel Dda University Health Board

Haverfordwest, , United Kingdom

Site Status

Wycombe Hospital, Buckinghamshire Healthcare NHS Trust

High Wycombe, , United Kingdom

Site Status

Queen Elizabeth Hospital Kings Lynn NHS Trust

Kings Lynn, , United Kingdom

Site Status

Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust

Leicester, , United Kingdom

Site Status

Royal Liverpool and Broadgreen University Hospitals NHS Trust

Liverpool, , United Kingdom

Site Status

Prince Philip Hospital, Hywel Dda University Health Board

Llanelli, , United Kingdom

Site Status

The Royal London Hospital, Barts Health NHS Trust

London, , United Kingdom

Site Status

Northwick Park Hospital, London North West Healthcare NHS Trust

London, , United Kingdom

Site Status

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Site Status

St George's University Hospitals NHS Foundation Trust

London, , United Kingdom

Site Status

Charing Cross Hospital, Imperial College Healthcare NHS Trust

London, , United Kingdom

Site Status

Luton and Dunstable University Hospital NHS Foundation Trust

Luton, , United Kingdom

Site Status

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

Middlesbrough, , United Kingdom

Site Status

Milton Keynes University Hospital NHS Foundation Trust

Milton Keynes, , United Kingdom

Site Status

Nottingham University Hospitals NHS Trust

Nottingham, , United Kingdom

Site Status

Derriford Hospital University Hospitals Plymouth NHS Trust

Plymouth, , United Kingdom

Site Status

Poole Hospital NHS Foundation Trust

Poole, , United Kingdom

Site Status

Royal Preston Hospital, Lancashire Teaching Hospitals

Preston, , United Kingdom

Site Status

Royal Berkshire NHS Foundation Trust

Reading, , United Kingdom

Site Status

Salford Royal Hospital, Salford Royal NHS Foundation Trust

Salford, , United Kingdom

Site Status

Salisbury District Hospital, Salisbury NHS Foundation Trust

Salisbury, , United Kingdom

Site Status

Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, , United Kingdom

Site Status

University Hospital Southampton NHS Foundation Trust

Southampton, , United Kingdom

Site Status

Southend University Hospital NHS Foundation Trust

Southend-on-Sea, , United Kingdom

Site Status

Kings Mill Hospital, Sherwood Forest Hospitals NHS Foundation Trust

Sutton in Ashfield, , United Kingdom

Site Status

Morriston Hospital, Swansea Bay University Health Board

Swansea, , United Kingdom

Site Status

Torbay Hospital, Torbay and South Devon NHS Foundation

Torquay, , United Kingdom

Site Status

Arrowe Park Hospital, Wirral University Teaching Hospital NHS Foundation Trust

Upton, , United Kingdom

Site Status

Watford General Hospital, West Hertfordshire Hospitals NHS Trust

Watford, , United Kingdom

Site Status

Royal Hampshire County Hospital, Hampshire Hospitals NHS Foundation Trust

Winchester, , United Kingdom

Site Status

Wrexham Maelor Hospital, Betsi Cadwaladr University Health Board

Wrexham, , United Kingdom

Site Status

York Teaching Hospital NHS Foundation Trust

York, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 40402086 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39966982 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39491870 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35018878 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

18/0316

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.