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Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST2)

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ClinicalTrials.gov Identifier: NCT02814409
Recruitment Status : Recruiting
First Posted : June 27, 2016
Last Update Posted : March 29, 2018
Sponsor:
Collaborators:
University of Glasgow
University of Edinburgh
Oxford University Hospitals NHS Trust
Information provided by (Responsible Party):
NHS Greater Glasgow and Clyde

Tracking Information
First Submitted Date  ICMJE June 23, 2016
First Posted Date  ICMJE June 27, 2016
Last Update Posted Date March 29, 2018
Actual Study Start Date  ICMJE December 15, 2016
Estimated Primary Completion Date August 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 23, 2016)
modified Rankin Scale [ Time Frame: Day 90 (+/- 7) ]
modified Rankin Scale (mRS) at day 90, determined by the Rankin Focused Assessment (RFA) method using centralised telephone interview, analysed by ordinal distribution ("shift") analysis of the scores in intervention and control groups.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02814409 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 21, 2016)
  • Full neurological recovery (modified Rankin Scale 0-1 versus 2-6). [ Time Frame: Day 90 (+/- 7) ]
  • Independent recovery (modified Rankin Scale score 0-2 versus 3-6). [ Time Frame: Day 90 (+/- 7) ]
  • Early major neurological improvement of 8 or more points, or return to the National Institutes of Health Stroke Scale (NIHSS) total score of 0 or 1 at 24 hour(s). [ Time Frame: 24 hours ]
  • Health Related Quality of Life (EuroQol five dimensions questionnaire, EQ-5D) [ Time Frame: Day 90 (+/- 7) ]
  • Barthel Index score [ Time Frame: Day 90 (+/- 7) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 23, 2016)
  • Full neurological recovery (mRS 0-1 versus 2-6). [ Time Frame: Day 90 (+/- 7) ]
  • Independent recovery (mRS score 0-2 versus 3-6). [ Time Frame: Day 90 (+/- 7) ]
  • Early major neurological improvement of 8 or more points, or return to NIHSS total score of 0 or 1 at 24 h. [ Time Frame: 24 hours ]
  • Health Related Quality of Life (EQ-5D) [ Time Frame: Day 90 (+/- 7) ]
  • Barthel Index score [ Time Frame: Day 90 (+/- 7) ]
Current Other Pre-specified Outcome Measures
 (submitted: September 21, 2016)
  • Mortality [ Time Frame: Day 90 (+/- 7) ]
  • Imaging scan up to 36 hours, combined with a neurological deterioration NIHSS≥4 points from baseline (or lowest NIHSS value baseline-24 h), or leading to death (Safe Implementation of Thrombolysis in Stroke-Monitoring study definition). [ Time Frame: 36 hours ]
  • Symptomatic Intra-Cerebral Haemorrhage (SICH) by (European Cooperative Acute Stroke Study) ECASS-2 and ECASS-3 definitions. [ Time Frame: up to day 90 ]
  • Parenchymal Haematoma type 2 (PH2) haemorrhage on post-treatment computerised tomography (CT) scan up to 36 hours after treatment. [ Time Frame: 36 hours ]
  • Intracranial haemorrhage [ Time Frame: 22-36 hours ]
    Any intracranial haemorrhage on 22-36 hours computerised tomography (CT) scan
  • Significant extracranial haemorrhage (requirement for blood transfusion or drop in haemoglobin of ≥20mg/l in the 36h after treatment). [ Time Frame: 36 hours ]
Original Other Pre-specified Outcome Measures
 (submitted: June 23, 2016)
  • Mortality [ Time Frame: Day 90 (+/- 7) ]
  • Imaging scan up to 36h, combined with a neurological deterioration NIHSS ≥4 points from baseline (or lowest NIHSS value baseline-24 h), or leading to death (SITS-MOST definition). [ Time Frame: 36 hours ]
  • SICH by ECASS-2 and ECASS-3 definitions. [ Time Frame: up to day 90 ]
  • PH2 haemorrhage on post-treatment CT up to 36h after treatment. [ Time Frame: 36 hours ]
  • Intracranial haemorrhage [ Time Frame: 22-36 hours ]
    Any intracranial haemorrhage on 22-36h CT
  • Significant extracranial haemorrhage (requirement for blood transfusion or drop in haemoglobin of ≥20mg/l in the 36h after treatment). [ Time Frame: 36 hours ]
 
Descriptive Information
Brief Title  ICMJE Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis
Official Title  ICMJE Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST 2)
Brief Summary The principle research question is: in patients with acute ischaemic stroke eligible for intravenous (IV) thrombolysis, is tenecteplase superior in efficacy to alteplase, based on functional outcome as assessed by modified Rankin Scale distribution at day 90?
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Ischemic Stroke
Intervention  ICMJE
  • Drug: Intravenous recombinant tissue plasminogen activator (rtPA) Alteplase
  • Drug: Intravenous Tenecteplase
Study Arms  ICMJE
  • Active Comparator: Alteplase - standard care
    Alteplase 0.9 mg/kg with 10% of the total dose administered as an initial intravenous bolus and remaining 90% of the total dose administered as an intravenous infusion over 1 hour (maximum dose 90mg).
    Intervention: Drug: Intravenous recombinant tissue plasminogen activator (rtPA) Alteplase
  • Experimental: Tenecteplase
    Tenecteplase 0.25mg/kg administered as a single rapid intravenous bolus (maximum dose 25mg).
    Intervention: Drug: Intravenous Tenecteplase
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 23, 2016)
1870
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2019
Estimated Primary Completion Date August 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  • Eligible for intravenous thrombolysis.
  • Male or non-pregnant female ≥18 years of age.
  • <4.5h after symptom onset.
  • Consent of patient or legal representative.
  • Independent prior to the stroke (estimated modified Rankin Scale 0-1).

Exclusion criteria:

  • Eligible for intravenous thrombolysis: Evidence of intracranial haemorrhage or significant non-stroke intracranial pathology likely to account for clinical presentation or represent a risk of intracerebral haemorrhage (eg Central Nervous System neoplasm) on pre-treatment computerised tomography (CT) scan; Stroke within the previous 14 days, thrombolytic therapy within the past 14 days, or hypodensity on pre-treatment computerised tomography (CT) scan consistent with recent cerebral ischaemia other than the presenting event; Systolic blood pressure more than 185 or diastolic blood pressure more than 110 mmHg, or aggressive management (intravenous pharmacotherapy) necessary to reduce blood pressure to these limits; Clinical history suggestive of subarachnoid haemorrhage even if no blood is evident on computerised tomography (CT) scan; High risk of haemorrhage, including major surgery, trauma or gastrointestinal or urinary tract haemorrhage within the previous 21 days; Arterial puncture at a non-compressible site within the previous 7 days; Prolonged cardiopulmonary resuscitation (> 2 minutes) within the previous 14 days; Acute pericarditis and/or subacute bacterial endocarditis; acute pancreatitis; Severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) and active hepatitis; Active peptic ulceration; Known history of haemorrhagic stroke; Known defect of clotting or platelet function (other than antiplatelet therapy); Hypo- or hyperglycaemia (blood glucose <2 mmol/l or >18 mmol/l) sufficient to account for neurological symptoms; Seizure at onset of symptoms unless brain imaging identifies positive evidence of significant brain ischaemia (eg early ischaemic change or hyperdense vessel on plain computerised tomography (CT) scan, computerised tomography angiography (CTA) scan confirmed arterial occlusion); Pregnancy (for women of child-bearing potential a negative pregnancy test will be required prior to randomisation); Inadequate haemostasis: Taking warfarin and international normalised ratio (INR) >1.3, Taking a Direct Oral Anticoagulant (dabigatran, rivaroxaban, apixaban, edoxaban) unless known to be >12 hours since last dose and with normal coagulation assays, Low molecular weight heparin (at doses other than prophylaxis of venous thromboembolism) administered within the preceding 48 hours, Unfractionated heparin administered within the previous 48 hours and activated partial thromboplastin time (APTT) is prolonged.
  • Acute endovascular treatment for stroke planned.
  • Any major medical condition likely to limit survival to day 90.
  • Unavailable for day 90 follow-up.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Alicia Murray, BSc, PhD Alicia.Murray@glasgow.ac.uk
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02814409
Other Study ID Numbers  ICMJE NorthGlasgowU
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party NHS Greater Glasgow and Clyde
Study Sponsor  ICMJE NHS Greater Glasgow and Clyde
Collaborators  ICMJE
  • University of Glasgow
  • University of Edinburgh
  • Oxford University Hospitals NHS Trust
Investigators  ICMJE
Principal Investigator: Keith Muir, MD, FRCP University of Glasgow
PRS Account NHS Greater Glasgow and Clyde
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP