ATTEST 2: A trial comparing the new clot busting drug treatment tenecteplase with standard clot busting treatment

Phase 1

• Conditions: Acute ischaemic stroke; MedDRA version: 21.1Level: PTClassification code 10061256Term: Ischaemic strokeSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2016-002075-10-GB
• Lead Sponsor: HS Greater Glasgow & Clyde

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-09-14
• Last Update Posted: 16 December 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 1870

Inclusion Criteria

1) Eligible for IV thrombolysis.
2) Male or non-pregnant female =18 years of age.
3) <4.5h after symptom onset.
4) Consent of patient or legal representative.
5) Independent prior to the stroke (estimated mRS 0-2).

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 600
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1300

Exclusion Criteria

1) Contraindications to thrombolytic therapy:
(i) Evidence of intracranial haemorrhage or significant non-stroke intracranial pathology likely to account for clinical presentation or represent a risk of intracerebral haemorrhage (eg CNS neoplasm) on pre-treatment CT
(ii) Stroke within the previous 14 days, thrombolytic therapy within the past 14 days, or hypodensity on pre-treatment CT consistent with recent cerebral ischaemia other than the presenting event
(iii) systolic blood pressure >185 or diastolic BP >110 mm Hg, or aggressive management (intravenous pharmacotherapy) necessary to reduce BP to these limits
(iv) Clinical history suggestive of subarachnoid haemorrhage even if no blood is evident on CT
(v) 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 (> 2minutes) 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)
(vi) Hypo- (< 50 mg/dL or <2.8 mmol/L) or hyperglycaemia (>400 mg/dL or >22.2 mmol/L) sufficient to account for neurological symptoms.
(vii) Seizure at onset of symptoms unless brain imaging identifies positive evidence of significant brain ischaemia (eg early ischaemic change or hyperdense vessel on plain CT, CTA confirmed arterial occlusion)
(viii) Pregnancy (For women of child-bearing potential a negative pregnancy test will be required prior to randomisation).
(ix) Inadequate haemostasis:
?- Taking warfarin and 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 APTT is prolonged.
2) Any major medical condition likely to limit survival to day 90.
3) Unavailable for day 90 follow-up.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The principle research question is: in patients with acute ischaemic stroke eligible for IV thrombolysis, is tenecteplase superior in efficacy to alteplase, based on functional outcome as assessed by modified Rankin Scale distribution at day 90?<br><br>;Secondary Objective: Secondary research questions are concerned with the safety of tenecteplase, including: is tenecteplase associated with a lower risk of symptomatic ICH compared to alteplase?;Primary end point(s): The primary outcome is 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 of scores in intervention and control groups.;Timepoint(s) of evaluation of this end point: Day 90 after stroke