Head Down Tilt 15° to Increase Collateral Flow in Acute Ischemic Stroke: a Multicenter, Randomised, Proof of Concept, Phase 2a/b Trial in Patients Treated With Mechanical Thrombectomy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 118
- 试验地点
- 12
- 主要终点
- Good collateral status
研究概览
简要总结
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°).
详细描述
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°; N=119), versus those with a HDT15 position (0 to -15°; N=90). 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
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 (collateral status, assessed during the pretreatment diagnostic angiographic series of mechanical thrombectomy)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Acute ischemic stroke due to left or right MCA occlusion of the M1 segment (excluding occlusion of the internal carotid artery terminus + M1)
- •Decision to treat with mechanical thrombectomy (with or without intravenous thrombolysis)
- •Informed consent obtained from patient or patient's next of kin, or emergency consent procedure
排除标准
- •Impaired consciousness, defined as NIHSS score of 2 or 3 of the item 1a (level of consciousness): not alert, requires repeated stimulation or unresponsive.
- •Vomiting upon stroke onset.
- •History of glaucoma.
- •History or imaging findings of intracranial hypertension of any aetiology
- •Major breath disorders, defined as follows:
- •oxygen saturation ≤92% in room air at admission
- •severe chronic obstructive pulmonary disease (COPD) treated with long-term oxygen therapy.
- •severe heart failure with NYHA class 3 or 4 (breathlessness during ordinary physical activity or at rest).
- •Severe obesity, defined as body mass index (BMI) >
- •Patients participating in another interventional trial that would interfere with this study.
- •Female patients who are pregnant
研究组 & 干预措施
HEAD DOWN TILT -10° to -15° (HDT15)
HDT15 will be applied in the intervention group in 2 different settings:
- in the Emergency Room, by tilting the stretcher to lower the head by -10° to -15° relative to the body of the patient; the degree of tilting will be checked using a dedicated digital inclinometer or a mobile phone app
- in the Angiography Suite, by tilting the angiography table to lower the head by -10° to -15° relative to the body of the patient, depending on the actual technology of the angiography system of each clinical site; the degree of tilting will be automatically checked using the angiography system HDT15 will start as soon as possible following randomisation in the Emergency Room (i.e. after vascular neuroimaging), and will be maintained during the transfer to the Angiography Suite, as well as during the entire thrombectomy procedure. HDT15 will end after the completion of mechanical thrombectomy.
干预措施: HEAD DOWN TILT -10° to -15° (Procedure)
USUAL POSITIONING
Patients randomised in the control group will be maintained in the usual position during the emergency room phase (0° to +30°) and on the angiography table (0°), according to standard practice. Mechanical thrombectomy will be performed as per usual care.
结局指标
主要结局
Good collateral status
时间窗: Day 0 (during mechanical thrombectomy)
The primary endpoint will be the achievement of good collateral status, i.e. grade 3 or 4 on the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) collateral scale, in the HDT15 versus control group, as seen at the beginning of MT.15 The ASITN/SIR collateral grade will be assessed by a blinded central imaging core lab from the pretreatment diagnostic angiographic runs, routinely performed as the first procedural step of MT.
次要结局
- Aspiration pneumonia(1 day (24±12 hours))
- Neurological disability(3 months)
- Oxygen saturation(Day 0 (in the emergency room and angio suite))
- Vomiting(Day 0 (in the emergency room and angio suite))
- Systolic blood pressure(Day 0 (in the emergency room and angio suite))
- Diastolic blood pressure(Day 0 (in the emergency room and angio suite))
- Feasibility of HDT15(Day 0 (in the emergency room and angio suite))
- Delay to thrombectomy(Day 0 (in the emergency room and angio suite))
- Early neurological deterioration(1 day (24±12 hours))
- Symptomatic intracranial hemorrhage(1 day (24±12 hours))