<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03759938</url>
  </required_header>
  <id_info>
    <org_study_id>18/0316</org_study_id>
    <nct_id>NCT03759938</nct_id>
  </id_info>
  <brief_title>OPTIMAS: OPtimal TIMing of Anticoagulation After Acute Ischaemic Stroke : a Randomised Controlled Trial</brief_title>
  <acronym>OPTIMAS</acronym>
  <official_title>OPtimal TIMing of Anticoagulation After Acute Ischaemic Stroke: a Randomised Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University College, London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University College, London</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      OPTIMAS is a large, prospective, partially blinded randomised controlled trial of early&#xD;
      (within ≤4 days [96hrs]) or standard (between day 7 and day 14 after stroke onset) initiation&#xD;
      of anticoagulation after stroke in patients with atrial fibrillation (AF), using any licensed&#xD;
      dose of a direct oral anticoagulant (DOAC). The trial will use a non-inferiority gatekeeper&#xD;
      approach to test for non-inferiority of early anticoagulation followed by a test for&#xD;
      superiority, if non-inferiority is established.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Current guidelines do not provide clear recommendations on the timing of OAC after acute&#xD;
      AF-related stroke. Current United Kingdom (UK) guidelines for anticoagulation state that&#xD;
      &quot;delay for an arbitrary 2-week period is recommended&quot; for &quot;disabling&quot; stroke and that&#xD;
      anticoagulation can be started &quot;no later than 14 days&quot; for other strokes, at the prescriber's&#xD;
      discretion.&#xD;
&#xD;
      OPTIMAS will investigate whether early initiation of DOAC treatment, within 4 days (96hrs) of&#xD;
      onset, in patients with acute ischaemic stroke and AF is as effective as, or better than,&#xD;
      standard initiation of DOAC treatment, no sooner than day 7 (&gt;144hrs) and no later than day&#xD;
      14 (&lt;336hrs) after onset, in preventing recurrent ischaemic stroke, systemic embolism and&#xD;
      symptomatic intracranial haemorrhage (sICH)? Participants will be randomised 1:1 to the&#xD;
      intervention or control. The exact timing of initiating treatment within each group is at the&#xD;
      discretion of the treating clinician.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 18, 2019</start_date>
  <completion_date type="Anticipated">April 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">April 30, 2024</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_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</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>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.&#xD;
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.&#xD;
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.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Composite outcome of the combined incidence of:recurrent symptomatic ischaemic stroke,symptomatic intracranial haemorrhage and systemic embolism</measure>
    <time_frame>At 90 days from randomisation</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>All-cause mortality</measure>
    <time_frame>At 90 days from randomisation</time_frame>
    <description>All cause mortality reported in both arms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of vascular death</measure>
    <time_frame>At 90 days from randomisation</time_frame>
    <description>Any incidence of vascular death reported in both arms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of recurrent ischaemic stroke</measure>
    <time_frame>At 90 days from randomisation</time_frame>
    <description>Any incidence of recurrent ischaemic stroke reported in both arms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of systemic embolism</measure>
    <time_frame>At 90 days from randomisation</time_frame>
    <description>Any incidence of incidence of systemic embolism reported in both arms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of venous thromboembolism (deep vein thrombosis [DVT], pulmonary embolism [PE], cerebral venous thrombosis [CVT])</measure>
    <time_frame>At 90 days from randomisation</time_frame>
    <description>Any of Incidence of venous thromboembolism (deep vein thrombosis [DVT], pulmonary embolism [PE], cerebral venous thrombosis [CVT]) reported in both arms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional status assessed by the modified Rankin scale (mRS) in both arms</measure>
    <time_frame>At 90 days from randomisation</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive ability assessed by the Montreal Cognitive Assessment (MoCA) questionnaire in both arms</measure>
    <time_frame>At 90 days from randomisation</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life at 90 days assessed by EuroQol 5 Dimensions 5 level questionnaire [EQ-5D-5L] in both arms</measure>
    <time_frame>At 90 days from randomisation</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient reported outcomes assessed by the Patient-Reported Outcomes Measurement Information System Global Health questionnaire (PROMIS-10) in both arms.</measure>
    <time_frame>At 90 days from randomisation</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ongoing anticoagulation</measure>
    <time_frame>At 90 days from randomisation</time_frame>
    <description>Ongoing anticoagulation will be assessed based on patient self-reporting and follow up patient medical records if necessary in both arms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first incidence of primary outcome component (recurrent ischaemic stroke, systemic embolism, or sICH)</measure>
    <time_frame>At 90 days from randomisation</time_frame>
    <description>Time to first incidence of primary outcome component (recurrent ischaemic stroke, systemic embolism, or sICH) reported in both arms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay for stroke-related care</measure>
    <time_frame>At 90 days from randomisation</time_frame>
    <description>Length of hospital stay for stroke-related care in both arms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health and social care resource use</measure>
    <time_frame>At 90 days from randomisation</time_frame>
    <description>Health and social care resources (assessed by a study specific questionnaire) in both arms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of symptomatic intracranial haemorrhage (sICH)</measure>
    <time_frame>At 90 days from randomisation</time_frame>
    <description>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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of major extracranial bleeding</measure>
    <time_frame>At 90 days from randomisation</time_frame>
    <description>Incidence of major extracranial bleeding reported in both arms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of all major bleeding (intracranial and extracranial)</measure>
    <time_frame>At 90 days from randomisation</time_frame>
    <description>Incidence of all major bleeding (intracranial and extracranial) reported during the study period, in both arms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of clinically relevant non-major bleeding</measure>
    <time_frame>At 90 days from randomisation</time_frame>
    <description>Incidence of clinically relevant non-major bleeding reported in both arms</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Ongoing anticoagulation at 90 days</measure>
    <time_frame>At 90 days from randomisation</time_frame>
    <description>Ongoing anticoagulation at 90 days assessed by patient self-reporting and/ or follow up patient medical records if necessary.</description>
  </other_outcome>
  <other_outcome>
    <measure>Individual cognitive domain subscores</measure>
    <time_frame>At 90 days from randomisation</time_frame>
    <description>Individual cognitive domain subscores measured using the MoCA questionnaire</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">3478</enrollment>
  <condition>Stroke, Acute</condition>
  <condition>Atrial Fibrillation</condition>
  <arm_group>
    <arm_group_label>Early initiation of DOAC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard Initiation of DOAC</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Direct oral anticoagulant (DOAC)</intervention_name>
    <description>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.</description>
    <arm_group_label>Early initiation of DOAC</arm_group_label>
    <arm_group_label>Standard Initiation of DOAC</arm_group_label>
    <other_name>dabigatran, apixaban, edoxaban, rivaroxaban</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Aged 18 years or over&#xD;
&#xD;
          2. Clinical diagnosis of acute ischaemic stroke&#xD;
&#xD;
          3. AF, confirmed by any of:&#xD;
&#xD;
               1. 12-lead ECG recording&#xD;
&#xD;
               2. Inpatient ECG telemetry&#xD;
&#xD;
               3. Other prolonged ECG monitoring technique (e.g. Holter monitor)&#xD;
&#xD;
               4. Known diagnosis of atrial fibrillation verified by medical records (e.g. primary&#xD;
                  care records, letter from secondary care)&#xD;
&#xD;
          4. Eligibility to commence DOAC in accordance with approved prescribing recommendations&#xD;
             confirmed by treating physician&#xD;
&#xD;
          5. Uncertainty on the part of the treating physician regarding early versus standard&#xD;
             initiation of DOAC.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Contraindication to anticoagulation:&#xD;
&#xD;
               1. Coagulopathy or current or recent anticoagulation with vitamin K antagonist (VKA)&#xD;
                  leading to INR ≥1.7 at randomisation.&#xD;
&#xD;
               2. Thrombocytopenia (platelets &lt; 75 x 10⁹/L)&#xD;
&#xD;
               3. Other coagulopathy or bleeding tendency (based on clinical history or laboratory&#xD;
                  parameters) judged to contraindicate anticoagulation by treating clinician&#xD;
&#xD;
          2. Contraindication to early anticoagulation&#xD;
&#xD;
               1. Known presence of haemorrhagic transformation with parenchymal haematoma&#xD;
                  occupying &gt;30% of the infarct volume and exerting significant mass effect (i.e.&#xD;
                  PH2) (NB: HI1, HI2 and PH1 are not considered contraindications)&#xD;
&#xD;
               2. Presence of clinically significant intracranial haemorrhage unrelated to&#xD;
                  qualifying infarct&#xD;
&#xD;
               3. Any other contraindication to early anticoagulation as judged by the treating&#xD;
                  clinician&#xD;
&#xD;
          3. Contraindication to use of DOAC:&#xD;
&#xD;
               1. Known allergy or intolerance to both Factor Xa inhibitor and direct thrombin&#xD;
                  inhibitor&#xD;
&#xD;
               2. Definite indication for VKA treatment e.g. mechanical heart valve, valvular AF,&#xD;
                  antiphospholipid syndrome&#xD;
&#xD;
               3. Severe renal impairment with creatinine clearance (Cockcroft &amp; Gault formula) &lt;15&#xD;
                  mL/min (i.e. 14 mL/min or less)&#xD;
&#xD;
               4. Liver function tests ALT &gt; 2x ULN&#xD;
&#xD;
               5. Cirrhotic patients with Child Pugh score equating to grade B or C&#xD;
&#xD;
               6. Patient is taking medication with significant interaction with DOAC, including:&#xD;
&#xD;
                    -  Azole antifungals (e.g. ketoconazole, itraconazole)&#xD;
&#xD;
                    -  HIV protease inhibitors (e.g. ritonavir)&#xD;
&#xD;
                    -  Strong CYP3A4 inducers (e.g. rifampicin, phenytoin, carbamazepine,&#xD;
                       phenobarbital or St. John's Wort)&#xD;
&#xD;
                    -  Dronedarone&#xD;
&#xD;
          4. Pregnant or breastfeeding women&#xD;
&#xD;
          5. Presence on acute brain imaging of non-stroke pathology judged likely to explain&#xD;
             clinical presentation (e.g. mass lesion, encephalitis)&#xD;
&#xD;
          6. Inability for patient to be followed up within 90 days of trial entry&#xD;
&#xD;
          7. Patient or representative refusal to consent to study procedures, including the site&#xD;
             informing GP and healthcare professional responsible for anticoagulation care of&#xD;
             participants&#xD;
&#xD;
          8. Any other reason that the PI considers would make the patient unsuitable to enter&#xD;
             OPTIMAS.&#xD;
&#xD;
        Note that current DOAC treatment is NOT an exclusion criterion, as long as the treating&#xD;
        physician considers it appropriate to restart (or continue) according to the timings&#xD;
        specified in the OPTIMAS trial protocol. Continuation of the DOAC would be recorded as a&#xD;
        start time of zero hours.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David Werring, Prof</last_name>
    <role>Study Chair</role>
    <affiliation>UCL</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Marisa Chau</last_name>
    <phone>+44 20 7670 4618</phone>
    <phone_ext>64618</phone_ext>
    <email>ctu.optimas@ucl.ac.uk</email>
  </overall_contact>
  <location>
    <facility>
      <name>Bronglais General Hospital, Hywel Dda University Health Board</name>
      <address>
        <city>Aberystwyth</city>
        <zip>SY23 1ER</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Phil Jones</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal United Hospitals Bath NHS Foundation Trust</name>
      <address>
        <city>Bath</city>
        <zip>BA1 3NG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lukuman Gbadamoshi</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth Hospital,University Hospitals Birmingham NHS Foundation</name>
      <address>
        <city>Birmingham</city>
        <zip>B15 2TH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dom Sims</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal Bournemouth Hospital, Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust</name>
      <address>
        <city>Bournemouth</city>
        <zip>BH7 7DW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kamy Thavanesan</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Bradford Royal Infirmary, Bradford Teaching Hospitals NHS Foundation Trust</name>
      <address>
        <city>Bradford</city>
        <zip>BD9 6RJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stuart Maguire</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Broomfield Hospital, Mid Essex Hospital Services NHS Trust</name>
      <address>
        <city>Broomfield</city>
        <zip>CM1 7ET</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Madan Meegada</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>West Suffolk Hospital, West Suffolk NHS Foundation Trust</name>
      <address>
        <city>Bury Saint Edmunds</city>
        <zip>IP33 2QZ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Abul Azim</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Addenbrooke's Hospital NHS Trust</name>
      <address>
        <city>Cambridge</city>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eoin O'Brien</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Glangwili General Hospita, Hywel Dda University Health Boardl</name>
      <address>
        <city>Carmarthen</city>
        <zip>SA31 2AF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pagadala Sridhar</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>St Peter's Hospital, Ashford and St. Peter's Hospitals NHS Foundation Trust</name>
      <address>
        <city>Chertsey</city>
        <zip>KT16 0PZ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Giosue Gulli</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal Derby Hospital, University Hospitals of Derby and Burton NHS Foundation Trust</name>
      <address>
        <city>Derby</city>
        <zip>DE22 3NE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tim England</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal Devon &amp; Exeter NHS Foundation Trust</name>
      <address>
        <city>Exeter</city>
        <zip>EX2 5DW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Martin James</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Withybush General Hospital, Hywel Dda University Health Board</name>
      <address>
        <city>Haverfordwest</city>
        <zip>SA61 2PZ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christopher James</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Wycombe Hospital, Buckinghamshire Healthcare NHS Trust</name>
      <address>
        <city>High Wycombe</city>
        <zip>HP11 2TT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Maria Tuna</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth Hospital Kings Lynn NHS Trust</name>
      <address>
        <city>King's Lynn</city>
        <zip>PE30 4ET</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Raj Shekhar</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust</name>
      <address>
        <city>Leicester</city>
        <zip>LE1 5WW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eveson David</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal Liverpool and Broadgreen University Hospitals NHS Trust</name>
      <address>
        <city>Liverpool</city>
        <zip>L7 8XP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Aravind Manoj</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Prince Philip Hospital, Hywel Dda University Health Board</name>
      <address>
        <city>Llanelli</city>
        <zip>SA14 8QF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Senthil Subbarayan</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>The Royal London Hospital, Barts Health NHS Trust</name>
      <address>
        <city>London</city>
        <zip>E1 1FR</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sageet Amlani</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Northwick Park Hospital, London North West Healthcare NHS Trust</name>
      <address>
        <city>London</city>
        <zip>HA1 3UJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sumanjit Gill</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>University College London Hospitals NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <zip>NW1 2BU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>David Werring</last_name>
      <phone>020 3108 6255</phone>
      <email>d.werring@ucl.ac.uk</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>St George's University Hospitals NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <zip>SW17 0QT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Liqun Zhang</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Charing Cross Hospital, Imperial College Healthcare NHS Trust</name>
      <address>
        <city>London</city>
        <zip>W6 8RF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Soma Banerjee</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Luton and Dunstable University Hospital NHS Foundation Trust</name>
      <address>
        <city>Luton</city>
        <zip>LU4 0DZ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lakshmanan Sekaran</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>The James Cook University Hospital, South Tees Hospitals NHS Foundation Trust</name>
      <address>
        <city>Middlesbrough</city>
        <zip>TS4 3BW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Samer Al Hussayni</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Milton Keynes University Hospital NHS Foundation Trust</name>
      <address>
        <city>Milton Keynes</city>
        <zip>MK6 5LD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yousif Behnam</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Nottingham University Hospitals NHS Trust</name>
      <address>
        <city>Nottingham</city>
        <zip>NG7 2UH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ashit Shetty</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Derriford Hospital University Hospitals Plymouth NHS Trust</name>
      <address>
        <city>Plymouth</city>
        <zip>PL6 8DH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alex Shah</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Poole Hospital NHS Foundation Trust</name>
      <address>
        <city>Poole</city>
        <zip>BH15 2JB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Suzanne Ragab</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal Preston Hospital, Lancashire Teaching Hospitals</name>
      <address>
        <city>Preston</city>
        <zip>PR2 9HT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hedley Emsley</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal Berkshire NHS Foundation Trust</name>
      <address>
        <city>Reading</city>
        <zip>RG1 5AN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nagaratnam Kirubanathan</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Salford Royal Hospital, Salford Royal NHS Foundation Trust</name>
      <address>
        <city>Salford</city>
        <zip>M6 8HD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Amit Kishore</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Salisbury District Hospital, Salisbury NHS Foundation Trust</name>
      <address>
        <city>Salisbury</city>
        <zip>SP2 8BJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Toby Black</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust</name>
      <address>
        <city>Sheffield</city>
        <zip>S10 2JF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kirsty Harkness</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>University Hospital Southampton NHS Foundation Trust</name>
      <address>
        <city>Southampton</city>
        <zip>SO16 6YD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Richard Marigold</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Southend University Hospital NHS Foundation Trust</name>
      <address>
        <city>Southend-on-Sea</city>
        <zip>SS0 0RY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Paul Guyler</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Kings Mill Hospital, Sherwood Forest Hospitals NHS Foundation Trust</name>
      <address>
        <city>Sutton in Ashfield</city>
        <zip>NG17 4JL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Martin Cooper</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Morriston Hospital, Swansea Bay University Health Board</name>
      <address>
        <city>Swansea</city>
        <zip>SA6 6NL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Manju Krishnan</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Torbay Hospital, Torbay and South Devon NHS Foundation</name>
      <address>
        <city>Torquay</city>
        <zip>TQ2 7AA</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>John France</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Arrowe Park Hospital, Wirral University Teaching Hospital NHS Foundation Trust</name>
      <address>
        <city>Upton</city>
        <zip>CH49 5PE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Brian Menezes</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Watford General Hospital, West Hertfordshire Hospitals NHS Trust</name>
      <address>
        <city>Watford</city>
        <zip>WD18 0HB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mohit Bhandari</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal Hampshire County Hospital, Hampshire Hospitals NHS Foundation Trust</name>
      <address>
        <city>Winchester</city>
        <zip>SO22 5DG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lucy Sykes</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Wrexham Maelor Hospital, Betsi Cadwaladr University Health Board</name>
      <address>
        <city>Wrexham</city>
        <zip>LL 13 7TD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Walee Sayed</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>York Teaching Hospital NHS Foundation Trust</name>
      <address>
        <city>York</city>
        <zip>YO31 8HE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ruhail Mir</last_name>
    </contact>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>November 27, 2018</study_first_submitted>
  <study_first_submitted_qc>November 29, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 30, 2018</study_first_posted>
  <last_update_submitted>March 14, 2023</last_update_submitted>
  <last_update_submitted_qc>March 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ischaemic stroke, atrial fibrilation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
    <mesh_term>Ischemic Stroke</mesh_term>
    <mesh_term>Atrial Fibrillation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rivaroxaban</mesh_term>
    <mesh_term>Apixaban</mesh_term>
    <mesh_term>Edoxaban</mesh_term>
    <mesh_term>Dabigatran</mesh_term>
    <mesh_term>Anticoagulants</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03759938
org study id: 18/0316
nct id: NCT03759938
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
intervention 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
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: 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.
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
description: 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.
measure: All-cause mortality
time frame: At 90 days from randomisation
description: All cause mortality reported in both arms
measure: Incidence of vascular death
time frame: At 90 days from randomisation
description: Any incidence of vascular death reported in both arms
measure: Incidence of recurrent ischaemic stroke
time frame: At 90 days from randomisation
description: Any incidence of recurrent ischaemic stroke reported in both arms
measure: Incidence of systemic embolism
time frame: At 90 days from randomisation
description: Any incidence of incidence of systemic embolism reported in both arms
measure: Incidence of venous thromboembolism (deep vein thrombosis [DVT], pulmonary embolism [PE], cerebral venous thrombosis [CVT])
time frame: At 90 days from randomisation
description: Any of Incidence of venous thromboembolism (deep vein thrombosis [DVT], pulmonary embolism [PE], cerebral venous thrombosis [CVT]) reported in both arms
measure: Functional status assessed by the modified Rankin scale (mRS) in both arms
time frame: At 90 days from randomisation
description: 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.
measure: Cognitive ability assessed by the Montreal Cognitive Assessment (MoCA) questionnaire in both arms
time frame: At 90 days from randomisation
description: 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.
measure: Quality of life at 90 days assessed by EuroQol 5 Dimensions 5 level questionnaire [EQ-5D-5L] in both arms
time frame: At 90 days from randomisation
description: 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.
measure: Patient reported outcomes assessed by the Patient-Reported Outcomes Measurement Information System Global Health questionnaire (PROMIS-10) in both arms.
time frame: At 90 days from randomisation
description: 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.
measure: Ongoing anticoagulation
time frame: At 90 days from randomisation
description: Ongoing anticoagulation will be assessed based on patient self-reporting and follow up patient medical records if necessary in both arms
measure: Time to first incidence of primary outcome component (recurrent ischaemic stroke, systemic embolism, or sICH)
time frame: At 90 days from randomisation
description: Time to first incidence of primary outcome component (recurrent ischaemic stroke, systemic embolism, or sICH) reported in both arms
measure: Length of hospital stay for stroke-related care
time frame: At 90 days from randomisation
description: Length of hospital stay for stroke-related care in both arms
measure: Health and social care resource use
time frame: At 90 days from randomisation
description: Health and social care resources (assessed by a study specific questionnaire) in both arms
measure: Incidence of symptomatic intracranial haemorrhage (sICH)
time frame: At 90 days from randomisation
description: 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
measure: Incidence of major extracranial bleeding
time frame: At 90 days from randomisation
description: Incidence of major extracranial bleeding reported in both arms
measure: Incidence of all major bleeding (intracranial and extracranial)
time frame: At 90 days from randomisation
description: Incidence of all major bleeding (intracranial and extracranial) reported during the study period, in both arms
measure: Incidence of clinically relevant non-major bleeding
time frame: At 90 days from randomisation
description: Incidence of clinically relevant non-major bleeding reported in both arms
measure: Ongoing anticoagulation at 90 days
time frame: At 90 days from randomisation
description: Ongoing anticoagulation at 90 days assessed by patient self-reporting and/ or follow up patient medical records if necessary.
measure: Individual cognitive domain subscores
time frame: At 90 days from randomisation
description: Individual cognitive domain subscores measured using the MoCA questionnaire
arm group label: Early initiation of DOAC
arm group type: Experimental
description: 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
arm group label: Standard Initiation of DOAC
arm group type: Active Comparator
description: 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).
intervention type: Drug
intervention name: Direct oral anticoagulant (DOAC)
description: 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.
arm group label: Early initiation of DOAC
arm group label: Standard Initiation of DOAC
other name: dabigatran, apixaban, edoxaban, rivaroxaban
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: David Werring, Prof
role: Study Chair
affiliation: UCL
last name: Marisa Chau
phone: +44 20 7670 4618
phone ext: 64618
email: ctu.optimas@ucl.ac.uk
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status: Recruiting
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country: United Kingdom
responsible party type: Sponsor
mesh term: Stroke
mesh term: Ischemic Stroke
mesh term: Atrial Fibrillation
mesh term: Rivaroxaban
mesh term: Apixaban
mesh term: Edoxaban
mesh term: Dabigatran
mesh term: Anticoagulants
sharing ipd: No