OPtimal TIMing of Anticoagulation After Acute Ischaemic Stroke: a Randomised Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 3,648
- 试验地点
- 44
- 主要终点
- Composite outcome of the combined incidence of:recurrent symptomatic ischaemic stroke,symptomatic intracranial haemorrhage and systemic embolism
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
- •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.
排除标准
- •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:
- •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.
研究组 & 干预措施
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
干预措施: Direct oral anticoagulant (DOAC) (Drug)
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).
干预措施: Direct oral anticoagulant (DOAC) (Drug)
结局指标
主要结局
Composite outcome of the combined incidence of:recurrent symptomatic ischaemic stroke,symptomatic intracranial haemorrhage and systemic embolism
时间窗: At 90 days from randomisation
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.
次要结局
- All-cause mortality(At 90 days from randomisation)
- Incidence of systemic embolism(At 90 days from randomisation)
- Incidence of vascular death(At 90 days from randomisation)
- Incidence of recurrent ischaemic stroke(At 90 days from randomisation)
- Functional status assessed by the modified Rankin scale (mRS) in both arms(At 90 days from randomisation)
- Quality of life at 90 days assessed by EuroQol 5 Dimensions 5 level questionnaire [EQ-5D-5L] in both arms(At 90 days from randomisation)
- Incidence of symptomatic intracranial haemorrhage (sICH)(At 90 days from randomisation)
- Incidence of major extracranial bleeding(At 90 days from randomisation)
- Incidence of clinically relevant non-major bleeding(At 90 days from randomisation)
- Cognitive ability assessed by the Montreal Cognitive Assessment (MoCA) questionnaire in both arms(At 90 days from randomisation)
- Incidence of all major bleeding (intracranial and extracranial)(At 90 days from randomisation)
- Time to first incidence of primary outcome component (recurrent ischaemic stroke, systemic embolism, or sICH)(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)
- Ongoing anticoagulation(At 90 days from randomisation)
- Length of hospital stay for stroke-related care(At 90 days from randomisation)
- Health and social care resource use(At 90 days from randomisation)
- Patient reported outcomes assessed by the Patient-Reported Outcomes Measurement Information System Global Health questionnaire (PROMIS-10) in both arms.(At 90 days from randomisation)