Ignite Creation Date:
2024-05-06 @ 8:13 PM
Last Modification Date:
2024-10-26 @ 3:23 PM
Study NCT ID:
NCT06297863
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-03-07
First Post:
2024-02-26
Brief Title:
Head Down Tilt 15 to Increase Collateral Flow in Acute Ischemic Stroke
Sponsor:
University of Milano Bicocca
Organization:
University of Milano Bicocca
Study Overview
Official Title:
Head Down Tilt 15 to Increase Collateral Flow in Acute Ischemic Stroke a Multicenter Randomised Proof of Concept Phase 2ab Trial in Patients Treated With Mechanical Thrombectomy
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DOWN-SUITE
Brief Summary:
The DOWN-SUITE study is multicenter randomised controlled open-label clinical trial with blinded outcome assessment comparing collateral status in patients with acute ischemic stroke treated with an in-hospital application of head down tilt -10 to -15 HDT15 versus usual positioning 0 to 30 before endovascular mechanical thrombectomy
This study will involve adult patients who are eligible for mechanical thrombectomy and who have acute ischemic stroke due to left or right middle cerebral artery occlusion M1 segment
The investigators hypothesise that HDT15 applied in acute ischemic stroke patients with a large vessel occlusion will improve collateral circulation prolong the survival of the ischemic penumbra and improve the clinical benefit from mechanical thrombectomy compared with standard of care usual positioning 0 to 30
This study will involve adult patients who are eligible for mechanical thrombectomy and who have acute ischemic stroke due to left or right middle cerebral artery occlusion M1 segment
The investigators hypothesise that HDT15 applied in acute ischemic stroke patients with a large vessel occlusion will improve collateral circulation prolong the survival of the ischemic penumbra and improve the clinical benefit from mechanical thrombectomy compared with standard of care usual positioning 0 to 30
Detailed Description:
Investigating developing and implementing a collateral therapeutic is a major objective in stroke research The aim is to increase the amount of potentially salvageable penumbral tissue and expand the tissue time window thus increasing the efficacy of reperfusion therapies and improving clinical outcomes
Head down tilt 15 HDT15 is a positional therapy consisting of tilting the patient with the head 15 degrees below the rest of the body Experimental studies from an Italian-French group Dr Simone Beretta Fondazione IRCCS San Gerardo dei Tintori and Prof Tae-Hee Cho Hospices Civils de Lyon showed that HDT15 increased cerebral blood flow and improved functional outcome and infarct volume in randomised rats with middle cerebral artery MCA occlusion followed by reperfusion Subsequent perfusion MRI experiments using the same stroke model by our group confirmed that HDT15 application for 60 minutes significantly increases collateral flow in the ischemic area
There is no consensus in current clinical practice regarding the most appropriate head position for acute ischemic stroke AIS patients The sitting position at 30 is the most common An international cluster-randomised trial HeadPoST randomised over 11000 patients with acute stroke 85 ischemic to either a lying-flat position or a sitting-up position head elevated to at least 30 maintained for 24 hours No difference in the primary efficacy outcome disability at 90 days measured with the modified Rankin Scale mRS mortality or rates of other serious adverse events including pneumonia were observed However the HeadPoST trial primarily targeted patients with mild symptoms without a large vessel occlusion LVO who were randomised beyond the usual time window of reperfusion therapies
One retrospective study pre-thrombectomy era compared two cohorts of AIS patients with a LVO patients with a standard position 0 to 30 N119 versus those with a HDT15 position 0 to -15 N90 The results suggested that HDT15 promotes neurological improvement compared to the standard position No difference in serious adverse events was observed between the two cohorts
A recent randomized pilot clinical trial showed promising results of -20 head down positioning on long-term disability and an excellent safety profile
Thus the available clinical evidence raised no safety concern for HDT15 in AIS patients but data on its efficacy notably among AIS patients treated by MT remains insufficient HDT15 for its simplicity low cost and feasibility might be an optimal collateral therapeutic candidate to prolong the survival of the ischemic penumbra and improve the clinical benefit from reperfusion therapies with disability reduction HDT15 is readily feasible by Emergency Services in the prehospital phase of AIS before reperfusion therapies
The DOWN-SUITE study will be the first multicenter randomised controlled open-label clinical trial with blinded outcome assessment comparing collateral status in patients with AIS treated with an in-hospital application of HDT15 versus usual positioning before MT The duration of HDT15 application approximately 60-90 minutes is expected to be long enough to detect significant changes in cerebral hemodynamics Building from preclinical experiments on rodent and non-human primate stroke models carried out by our French-Italian group it will provide for the first time the translation of HDT15 efficacy on cerebral hemodynamics and clinical outcome from animal models to AIS patients
No therapeutic intervention is currently available to enhance collaterals in AIS
The DOWN-SUITE trial will provide robust high-quality evidence on the safety feasibility and efficacy of HDT15 as a low-cost collateral therapeutic for AIS
The investigators hypothesise that HDT15 -10 to -15 applied in AIS patients with an LVO will improve collateral circulation prolong the survival of the ischemic penumbra and improve the clinical benefit from MT compared with standard of care usual positioning 0 to 30
The investigators aim to perform a prospective multicenter proof of concept randomised controlled open-label study As a double-blind is not possible a blinded central imaging core lab whose members will be unaware of the procedure assignments will assess all imaging outcomes including the primary efficacy outcome
This study will involve adult patients who are eligible for MT and who have AIS due to left or right MCA occlusion M1 segment
Benefitrisk ratio The investigators hypothesise that HDT15 would improve cerebral collaterals in patients randomised in the intervention group which could subsequently reduce the ischemic injury and improve the clinical outcome
No harm from participating in DOWN-SUITE is expected for patients in the intervention or control groups Previous clinical data on HDT15 raised no safety concerns No difference in post-stroke complications including cerebral oedema or haemorrhage pneumonia or mortality was observed in a retrospective observational study HDT15 is not expected to interfere with standard care including the procedural steps of MT Mild discomfort related to the tilted position may occur in some patients The treating physician will continuously monitor all patients during the entire duration of the HDT15 application No additional risk is expected in patients in the control group as they will receive standard care
Overall this studys benefitrisk ratio is considered very favourable
This study could potentially establish HDT15 as the first evidence-based collateral therapeutic for AIS No therapeutic intervention is currently available to enhance collaterals in the acute phase of ischemic stroke Such a collateral-enhancing therapy is necessary to expand the time window and increase the probability of successful reperfusion with IVT and MT resulting in better clinical outcomes
The results of the DOWN-SUITE trial may pave the way for larger randomised controlled trials of HDT15 in a wider stroke patient population such as patients transferred from spoke hospitals to hub stroke centers to receive thrombectomy and unselected patients with suspected AIS in the prehospital setting
Head down tilt 15 HDT15 is a positional therapy consisting of tilting the patient with the head 15 degrees below the rest of the body Experimental studies from an Italian-French group Dr Simone Beretta Fondazione IRCCS San Gerardo dei Tintori and Prof Tae-Hee Cho Hospices Civils de Lyon showed that HDT15 increased cerebral blood flow and improved functional outcome and infarct volume in randomised rats with middle cerebral artery MCA occlusion followed by reperfusion Subsequent perfusion MRI experiments using the same stroke model by our group confirmed that HDT15 application for 60 minutes significantly increases collateral flow in the ischemic area
There is no consensus in current clinical practice regarding the most appropriate head position for acute ischemic stroke AIS patients The sitting position at 30 is the most common An international cluster-randomised trial HeadPoST randomised over 11000 patients with acute stroke 85 ischemic to either a lying-flat position or a sitting-up position head elevated to at least 30 maintained for 24 hours No difference in the primary efficacy outcome disability at 90 days measured with the modified Rankin Scale mRS mortality or rates of other serious adverse events including pneumonia were observed However the HeadPoST trial primarily targeted patients with mild symptoms without a large vessel occlusion LVO who were randomised beyond the usual time window of reperfusion therapies
One retrospective study pre-thrombectomy era compared two cohorts of AIS patients with a LVO patients with a standard position 0 to 30 N119 versus those with a HDT15 position 0 to -15 N90 The results suggested that HDT15 promotes neurological improvement compared to the standard position No difference in serious adverse events was observed between the two cohorts
A recent randomized pilot clinical trial showed promising results of -20 head down positioning on long-term disability and an excellent safety profile
Thus the available clinical evidence raised no safety concern for HDT15 in AIS patients but data on its efficacy notably among AIS patients treated by MT remains insufficient HDT15 for its simplicity low cost and feasibility might be an optimal collateral therapeutic candidate to prolong the survival of the ischemic penumbra and improve the clinical benefit from reperfusion therapies with disability reduction HDT15 is readily feasible by Emergency Services in the prehospital phase of AIS before reperfusion therapies
The DOWN-SUITE study will be the first multicenter randomised controlled open-label clinical trial with blinded outcome assessment comparing collateral status in patients with AIS treated with an in-hospital application of HDT15 versus usual positioning before MT The duration of HDT15 application approximately 60-90 minutes is expected to be long enough to detect significant changes in cerebral hemodynamics Building from preclinical experiments on rodent and non-human primate stroke models carried out by our French-Italian group it will provide for the first time the translation of HDT15 efficacy on cerebral hemodynamics and clinical outcome from animal models to AIS patients
No therapeutic intervention is currently available to enhance collaterals in AIS
The DOWN-SUITE trial will provide robust high-quality evidence on the safety feasibility and efficacy of HDT15 as a low-cost collateral therapeutic for AIS
The investigators hypothesise that HDT15 -10 to -15 applied in AIS patients with an LVO will improve collateral circulation prolong the survival of the ischemic penumbra and improve the clinical benefit from MT compared with standard of care usual positioning 0 to 30
The investigators aim to perform a prospective multicenter proof of concept randomised controlled open-label study As a double-blind is not possible a blinded central imaging core lab whose members will be unaware of the procedure assignments will assess all imaging outcomes including the primary efficacy outcome
This study will involve adult patients who are eligible for MT and who have AIS due to left or right MCA occlusion M1 segment
Benefitrisk ratio The investigators hypothesise that HDT15 would improve cerebral collaterals in patients randomised in the intervention group which could subsequently reduce the ischemic injury and improve the clinical outcome
No harm from participating in DOWN-SUITE is expected for patients in the intervention or control groups Previous clinical data on HDT15 raised no safety concerns No difference in post-stroke complications including cerebral oedema or haemorrhage pneumonia or mortality was observed in a retrospective observational study HDT15 is not expected to interfere with standard care including the procedural steps of MT Mild discomfort related to the tilted position may occur in some patients The treating physician will continuously monitor all patients during the entire duration of the HDT15 application No additional risk is expected in patients in the control group as they will receive standard care
Overall this studys benefitrisk ratio is considered very favourable
This study could potentially establish HDT15 as the first evidence-based collateral therapeutic for AIS No therapeutic intervention is currently available to enhance collaterals in the acute phase of ischemic stroke Such a collateral-enhancing therapy is necessary to expand the time window and increase the probability of successful reperfusion with IVT and MT resulting in better clinical outcomes
The results of the DOWN-SUITE trial may pave the way for larger randomised controlled trials of HDT15 in a wider stroke patient population such as patients transferred from spoke hospitals to hub stroke centers to receive thrombectomy and unselected patients with suspected AIS in the prehospital setting
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None