None listed
Conditions
Brief summary
The distal ischaemic stroke thrombectomy against medical therapy trial is the last FRONTIER in stroke trial and builds on the success of Australian led thrombectomy trial, EXTEND IA. It is an Australian led trial in the Asia-Pacific region (FRONTIER-AP) which seeks to answer an important clinical conundrum on the optimal treatment approach for patients with clot in medium sized vessels (MVO) in the brain. Following the results of multiple randomized clinical trials some states in Australia have structured clinical pathways for treatment of patients with large vessel occlusion (LVO). Such knowledge does not exist for MVO. There is clinical equipoise to proceed with phase II clinical trials given the conflicting data from observations from multiple observational studies and small sample size of data from randomised clinical trial . Our primary hypothesis is that the clinical outcome of ischaemic stroke patients treated with endovascular therapy within 9 hours will be superior compared with that of standard medical therapy. This trial will require moderately large sample (n=240) and thus may not be achievable even in our large network of collaborators in Australia. We will leverage the opportunity provided by the International Clinical Trial Collaborations (ICTC) to recruit 50% of the patients for this trial by our international partners. If the trial shows superiority of thrombectomy for MVO then it may lead to significant restructuring of acute stroke care across multiple states as the current model of care is that hospitals that provide thrombolysis therapy can treat patients with MVO. In anticipation of this change we have built an implementation phase into this grant incorporating statistical analysis, health economics analysis, operational research and geospatial analysis. We will also seek support from Stroke Foundation and engage with their network of consumers to determine their perception of the impact on new model of care and other changes that they would like to see given their experiences These analyses will inform the scalability of our findings as well as design of phase III such that full implementation will be achievable. Within the first 12 months, we would have the trial registration, submit the trial to Australasian Stroke Trial Network, develop educational material for trialists and clinicians to recognise MVO, published protocol paper as well as recruitment of the initial group of patients .
Interventions
Patients randomised to the thrombectomy arm will have clot extraction by Stent retriever or aspiration catheter. This will be performed by certified interventional radiologist. In brief, it involves performing digital subtraction angiography, navigating the catheter to the site of the clot and performing the extraction. The procedure is anticipated to be around 1 hour but can take up to 2 hours on average. The standard care arm is alteplase or tenecteplase within 4.5 hours and between 4.5 - 9 hours, it’s alteplase or tenecteplase or best medical therapy according to the local guidelines. Post-intervention: A non-contrast Computed Tomography (CT) and CT Angiography will be performed 24 to 48 hr post intervention. At the investigator’s discretion, a repeat CT Perfusion or Magnetic Resonance Imaging (MRI) may be performed at 24 to 48 hr. For MRI (if used for baseline selection and at 24 to 48hrs), an initial scout view will be followed by isotropic Difiusion-weighted Imaging/DWI (created from DWI images obtained with diffusion sensitizing gradients applied in 3 orthogonal planes) using b values between 0 sec/mm2, equivalent to a T2-weighted image, and 1000 sec/mm2. Whole brain imaging will use 25 contiguous axial slices each 5 mm in thickness. The imaging time for DWI is approximately 3 minutes. Time of Flight MR Angiography will be obtained to determine the presence or absence of medium vessel occlusion (MVO). A T2*-weighted gradient echo sequence will be performed to assess for presence of intracerebral haemorrhage (ICH). A FLAIR sequence is also acquired. This protocol is identical between the acute and sub-acute (24 h) imaging.
Sponsors
Medical Research Future Fund International Clinical Trial and Cohort
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion criteria: 1. Patients presenting with acute ischaemic stroke within 9 hours of stroke onset 2. (NIHSS greater if equal to 5 or dysphasia if NIHSS less than 5) 3. Pre-stroke modified Rankin Score (mRS) score of 0 or 1 or 2 4. Patient’s age is equal or greater than 18 years (or as per local requirements) 5. Endovascular therapy expected to commence (arterial puncture) within 90 minutes of initial non-contrast CT brain. 6. Arterial occlusion on CT Angiography (CTA) or MR Angiography (MRA) of the M2 (proximal, mid or distal), M3, A1, and A2.
Exclusion criteria
Exclusion criteria: 1. Patients presenting with acute ischaemic stroke >9 hours of stroke onset 2. Intracranial haemorrhage (ICH) identified by CT or MRI 3. Rapidly improving symptoms at the discretion of the investigator 4. Pre-stroke modified Rankin Score (mRS) score of greater than 2 (indicating previous disability) 5. Hypodensity in >1/2 MCA or ACA territory on non-contrast CT 6. ICA occlusion ipsilateral to the distal MCA or ACA clot 7. Contraindication to imaging with contrast agents 8. Any terminal illness such that the patient would not be expected to survive more than 1 year. 9. Patients with active cancer and undergoing treatment for cancer are excluded, 10. Any condition that, in the judgment of the investigator, could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study. 11. Pregnant women
Outcome results
None listed