Acute Ischemic StrokePhase 2DOWN-SUITENCT06297863
Head Down Tilt 15° to Increase Collateral Flow in Acute Ischemic Stroke
A Phase 2 study testing HEAD DOWN TILT -10° to -15° in people with Acute Ischemic Stroke, run by University of Milano Bicocca at 6 sites in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Ischemic Stroke
- What is being tested?
- HEAD DOWN TILT -10° to -15°
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 118 participants
- Where
- 6 sitesItaly
- Study dates
- 1 Mar 2025to 31 Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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) > 35.
- Patients participating in another interventional trial that would interfere with this study.
- Female patients who are pregnant
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
BiCRO (academic CRO) contact
6 sites in 1 country
Italy6 sites, 6 recruiting
- Not yet recruiting
Ospedale Civile SS. Nicola e Filippo Avezzano Pronto Soccorso
Avezzano, 67051
Simona Sacco, MD, PhD
- Not yet recruiting
Azienda Ospedaliero Universitaria Careggi
Florence, 50134
Enrico Fainardi, MD, PhD
- Not yet recruiting
Azienda Ospedaliera Policlinico Universitario "G. Martino"
Messina, 98124
Sergio Vinci, MD, PhD
- Recruiting
Fondazione IRCCS San Gerardo dei Tintori Monza
Monza, 20900
Simone Beretta, MD, PhD
- Not yet recruiting
Azienda Ospedaliero Universitaria Policlinico Umberto I
Roma, 00161
Danilo Toni, MD, PhD
- Not yet recruiting
Ospedale Santa Maria della Misericordia
Udine, 33100
Francesco Janes, MD, PhD
About this study
Official title: 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
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°).
Read the 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°; 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.
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).
Benefit/risk 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 study's benefit/risk 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.
- Conditions
- Acute Ischemic Stroke
- Being tested
- HEAD DOWN TILT -10° to -15°
- Keywords
- Collaterals, Cerebral hemodynamics, Head down positioning
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HEAD DOWN TILT -10° to -15°Procedure or surgery
Head down tilt -10° to -15° (HDT15) is a positional therapy consisting of tilting the patient with the head -10° to -15° degrees below the rest of the body.
Application of HDT15 will not delay usual care. The standard in-hospital patient pathway, including transfer from neuroimaging room to the angiography suite and the required procedural steps of MT, will allow sufficient time for the application of HDT15. HDT15 duration is expected to be at least 30 minutes (estimated time 30 to 90 minutes), from start to the assessment of the primary efficacy endpoint.
The actual degree of HDT15 will be a range between -10° to -15°, depending on the angiographic system of each clinical site, but it will be maintained at -15° during the Emergency Room phase which is expected to account for >50% of the total application time.
| Study group | Role | What they receive |
|---|---|---|
| HEAD DOWN TILT -10° to -15° (HDT15) | Experimental | 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. Receives: Procedure: HEAD DOWN TILT -10° to -15° |
| USUAL POSITIONING | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Good collateral status
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.
Measured: Day 0 (during mechanical thrombectomy)
Secondary outcomes (10)
Feasibility of HDT15
proportion of patients randomised to the intervention group who are able to maintain HDT15 during the entire MT procedure
Measured: Day 0 (in the emergency room and angio suite)
Delay to thrombectomy
hospital admission-to-arterial access time (i.e. time to arterial puncture)
Measured: Day 0 (in the emergency room and angio suite)
Vomiting
Proportion of patients presenting one or more episodes of vomiting from randomisation to the completion of MT
Measured: Day 0 (in the emergency room and angio suite)
Early neurological deterioration
Proportion of patients who had increase of ≥4 points on the NIHSS score within 24±12 hours of the randomisation
Measured: 1 day (24±12 hours)
Symptomatic intracranial hemorrhage
Proportion of patients who had SICH per SITS-MOST definition within 24±12 hours: type 2 parenchymal hematoma with neurological deterioration of ≥4 points on the NIHSS
Measured: 1 day (24±12 hours)
Aspiration pneumonia
Proportion of patients with pneumonia within the first 72 hours after randomisation
Measured: 1 day (24±12 hours)
Neurological disability
functional outcome at 3 months, assessed with the ordinal score on the modified Rankin scale (shift across outcomes on the mRS between groups)
Measured: 3 months
Systolic blood pressure
Mean values of systolic blood pressure (mmHg) from hospital admission to the end of MT; monitored at entry in the Emergency Room, at entry in the angio suite and every 15 minutes from the start to the end of MT
Measured: Day 0 (in the emergency room and angio suite)
Diastolic blood pressure
Mean values of diastolic blood pressure (mmHg) from hospital admission to the end of MT; monitored at entry in the Emergency Room, at entry in the angio suite and every 15 minutes from the start to the end of MT
Measured: Day 0 (in the emergency room and angio suite)
Oxygen saturation
Mean values of oxygen saturation (%) from hospital admission to the end of MT; these physiological parameters will be monitored at entry in the Emergency Room, at entry in the angio suite and every 15 minutes from the start to the end of MT
Measured: Day 0 (in the emergency room and angio suite)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2024
- Study start1 Mar 2025
- Primary completion30 Sep 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Acute Ischemic StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The DOWN-SUITE trial is a prospective, multicenter, proof of concept, randomised, controlled, open label, phase 2a/b clinical trial with blinded outcome assessment, comparing cerebral collateral status in patients with acute ischemic stroke due to middle cerebral artery occlusion (M1 segment) treated with in-hospital application of HDT15 (-10° to -15°) versus usual positioning (0° to +30°), before and during mechanical thrombectomy.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 118 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Milano Bicocca
- Sponsor type
- University, hospital or other
- Collaborators
- Fondazione IRCCS San Gerardo dei Tintori, Azienda Ospedaliero-Universitaria Careggi, Azienda Ospedaliera Universitaria Policlinico "G. Martino", Azienda Ospedaliero Universitaria, Santa Maria della Misericordia di Udine, Italy, Università degli Studi dell'Aquila, Azienda Ospedaliero Universitaria Policlinico Umberto I, Roma
- Responsible party
- Sponsor
- Investigators
- Simone Beretta, MD, PhD, Principal investigator, University of Milano Bicocca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06297863
- Sponsor's protocol ID
- DOWN-SUITE
- Acronym
- DOWN-SUITE
- Status last verified
- Apr 2026
- First submitted
- 26 Feb 2024
- Last updated
- 6 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The project data can be accessed by interested European and extra-EU third parties for replication or further analysis only if given in a completely anonymous form. Third parties in this project include academic institutions, research centers and non-profit associations (e.g. research consortia). Third parties in this project do not include profit associations (e.g. drug companies).
Publications
Beretta S, Versace A, Carone D, Riva M, Dell'Era V, Cuccione E, Cai R, Monza L, Pirovano S, Padovano G, Stiro F, Presotto L, Paterno G, Rossi E, Giussani C, Sganzerla EP, Ferrarese C. Cerebral collateral therapeutics in acute ischemic stroke: A randomized preclinical trial of four modulation strategies. J Cereb Blood Flow Metab. 2017 Oct;37(10):3344-3354. doi: 10.1177/0271678X16688705. Epub 2017 Jan 23.
PubMed 28112023Diamanti S, Mariani J, Versace A, Riva M, Cuccione E, Cai R, Monza L, Vigano M, Bolbos R, Chauveau F, Cho TH, Carone D, Ferrarese C, Beretta S. Head down tilt 15 degrees to preserve salvageable brain tissue in acute ischemic stroke: A pre-clinical pooled analysis, with focus on cerebral hemodynamics. Eur J Neurosci. 2023 Jun;57(12):2149-2159. doi: 10.1111/ejn.15852. Epub 2022 Nov 4.
PubMed 36300727Anderson CS, Arima H, Lavados P, Billot L, Hackett ML, Olavarria VV, Munoz Venturelli P, Brunser A, Peng B, Cui L, Song L, Rogers K, Middleton S, Lim JY, Forshaw D, Lightbody CE, Woodward M, Pontes-Neto O, De Silva HA, Lin RT, Lee TH, Pandian JD, Mead GE, Robinson T, Watkins C; HeadPoST Investigators and Coordinators. Cluster-Randomized, Crossover Trial of Head Positioning in Acute Stroke. N Engl J Med. 2017 Jun 22;376(25):2437-2447. doi: 10.1056/NEJMoa1615715.
PubMed 28636854Gauthier A, Gerardin P, Renou P, Sagnier S, Debruxelles S, Poli M, Rouanet F, Olindo S, Sibon I. Trendelenburg Positioning in Large Vessel Ischaemic Stroke: A Pre-Post Observational Study Using Propensity Score Matching. Cerebrovasc Dis. 2018;46(1-2):24-32. doi: 10.1159/000490423. Epub 2018 Jul 27.
PubMed 30056454Chen HS, Zhang NN, Cui Y, Li XQ, Zhou CS, Ma YT, Zhang H, Jiang CH, Li RH, Wan LS, Jiao Z, Xiao HB, Li Z, Yan TG, Wang DL, Nguyen TN. A randomized trial of Trendelenburg position for acute moderate ischemic stroke. Nat Commun. 2023 May 5;14(1):2592. doi: 10.1038/s41467-023-38313-y.
PubMed 37147320Pedrazzini FA, Piergallini L, Diamanti S, Fainardi E, Vinci SL, Sozzi C, Fare M, Rossi E, Graziano F, Poggetti F, Mainini G, Giglio A, Magi A, Pederzoli G, Anzani A, De Bernardi E, Cerina V, Cho TH, Chauveau F, Carone D, Basso G, Citerio G, Sarti C, Limbucci N, Janes F, Casella C, Toscano A, Sacco S, Toni D, Remida P, Ferrarese C, Beretta S. Head Down Tilt 15 degrees to Increase Collateral Flow in Acute Ischemic Stroke: Rationale and Study Protocol of a Multicenter, Randomized, Proof-of-Concept, Phase 2a/b Trial in Patients Treated With Mechanical Thrombectomy (DOWN-SUITE). Stroke Vasc Interv Neurol. 2026 Feb 4;6(2):e002221. doi: 10.1161/SVIN.125.002221. eCollection 2026 Mar.
PubMed 41815317
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06297863
- Acronym / sponsor ID
- DOWN-SUITE / DOWN-SUITE
- Conditions
- Acute Ischemic Stroke
- Keywords
- Collaterals, Cerebral hemodynamics, Head down positioning
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 118 participants (estimated)
- Lead sponsor
- University of Milano BicoccaUniversity, hospital or other
- Collaborators
- Fondazione IRCCS San Gerardo dei Tintori, Azienda Ospedaliero-Universitaria Careggi, Azienda Ospedaliera Universitaria Policlinico "G. Martino", Azienda Ospedaliero Universitaria, Santa Maria della Misericordia di Udine, Italy, Università degli Studi dell'Aquila, Azienda Ospedaliero Universitaria Policlinico Umberto I, Roma
- Study start
- 1 Mar 2025 (actual)
- Primary completion
- 30 Sep 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 7 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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°).
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°; 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.
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).
Benefit/risk 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 study's benefit/risk 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- The DOWN-SUITE trial is a prospective, multicenter, proof of concept, randomised, controlled, open label, phase 2a/b clinical trial with blinded outcome assessment, comparing cerebral collateral status in patients with acute ischemic stroke due to middle cerebral artery occlusion (M1 segment) treated with in-hospital application of HDT15 (-10° to -15°) versus usual positioning (0° to +30°), before and during mechanical thrombectomy.
| Arm | Type | Receives |
|---|---|---|
| HEAD DOWN TILT -10° to -15° (HDT15) | Experimental | Procedure: HEAD DOWN TILT -10° to -15°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. |
| USUAL POSITIONING | No intervention | –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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (11 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HEAD DOWN TILT -10° to -15°Head down tilt -10° to -15° (HDT15) is a positional therapy consisting of tilting the patient with the head -10° to -15° degrees below the rest of the body. Application of HDT15 will not delay usual care. The standard in-hospital patient pathway, including transfer from neuroimaging room to the angiography suite and the required procedural steps of MT, will allow sufficient time for the application of HDT15. HDT15 duration is expected to be at least 30 minutes (estimated time 30 to 90 minutes), from start to the assessment of the primary efficacy endpoint. The actual degree of HDT15 will be a range between -10° to -15°, depending on the angiographic system of each clinical site, but it will be maintained at -15° during the Emergency Room phase which is expected to account for >50% of the total application time. | Procedure or surgery | HEAD DOWN TILT -10° to -15° (HDT15) |
Primary outcome
Good collateral status
Time frame: 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.
10 secondary outcomes
Feasibility of HDT15
Time frame: Day 0 (in the emergency room and angio suite)
Delay to thrombectomy
Time frame: Day 0 (in the emergency room and angio suite)
Vomiting
Time frame: Day 0 (in the emergency room and angio suite)
Early neurological deterioration
Time frame: 1 day (24±12 hours)
Symptomatic intracranial hemorrhage
Time frame: 1 day (24±12 hours)
Aspiration pneumonia
Time frame: 1 day (24±12 hours)
Neurological disability
Time frame: 3 months
Systolic blood pressure
Time frame: Day 0 (in the emergency room and angio suite)
Diastolic blood pressure
Time frame: Day 0 (in the emergency room and angio suite)
Oxygen saturation
Time frame: Day 0 (in the emergency room and angio suite)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
- Background: PubMed 28112023Beretta S, Versace A, Carone D, Riva M, Dell'Era V, Cuccione E, Cai R, Monza L, Pirovano S, Padovano G, Stiro F, Presotto L, Paterno G, Rossi E, Giussani C, Sganzerla EP, Ferrarese C. Cerebral collateral therapeutics in acute ischemic stroke: A randomized preclinical trial of four modulation strategies. J Cereb Blood Flow Metab. 2017 Oct;37(10):3344-3354. doi: 10.1177/0271678X16688705. Epub 2017 Jan 23.
- Background: PubMed 36300727Diamanti S, Mariani J, Versace A, Riva M, Cuccione E, Cai R, Monza L, Vigano M, Bolbos R, Chauveau F, Cho TH, Carone D, Ferrarese C, Beretta S. Head down tilt 15 degrees to preserve salvageable brain tissue in acute ischemic stroke: A pre-clinical pooled analysis, with focus on cerebral hemodynamics. Eur J Neurosci. 2023 Jun;57(12):2149-2159. doi: 10.1111/ejn.15852. Epub 2022 Nov 4.
- Background: PubMed 28636854Anderson CS, Arima H, Lavados P, Billot L, Hackett ML, Olavarria VV, Munoz Venturelli P, Brunser A, Peng B, Cui L, Song L, Rogers K, Middleton S, Lim JY, Forshaw D, Lightbody CE, Woodward M, Pontes-Neto O, De Silva HA, Lin RT, Lee TH, Pandian JD, Mead GE, Robinson T, Watkins C; HeadPoST Investigators and Coordinators. Cluster-Randomized, Crossover Trial of Head Positioning in Acute Stroke. N Engl J Med. 2017 Jun 22;376(25):2437-2447. doi: 10.1056/NEJMoa1615715.
- Background: PubMed 30056454Gauthier A, Gerardin P, Renou P, Sagnier S, Debruxelles S, Poli M, Rouanet F, Olindo S, Sibon I. Trendelenburg Positioning in Large Vessel Ischaemic Stroke: A Pre-Post Observational Study Using Propensity Score Matching. Cerebrovasc Dis. 2018;46(1-2):24-32. doi: 10.1159/000490423. Epub 2018 Jul 27.
- Background: PubMed 37147320Chen HS, Zhang NN, Cui Y, Li XQ, Zhou CS, Ma YT, Zhang H, Jiang CH, Li RH, Wan LS, Jiao Z, Xiao HB, Li Z, Yan TG, Wang DL, Nguyen TN. A randomized trial of Trendelenburg position for acute moderate ischemic stroke. Nat Commun. 2023 May 5;14(1):2592. doi: 10.1038/s41467-023-38313-y.
- Derived from this study: PubMed 41815317Pedrazzini FA, Piergallini L, Diamanti S, Fainardi E, Vinci SL, Sozzi C, Fare M, Rossi E, Graziano F, Poggetti F, Mainini G, Giglio A, Magi A, Pederzoli G, Anzani A, De Bernardi E, Cerina V, Cho TH, Chauveau F, Carone D, Basso G, Citerio G, Sarti C, Limbucci N, Janes F, Casella C, Toscano A, Sacco S, Toni D, Remida P, Ferrarese C, Beretta S. Head Down Tilt 15 degrees to Increase Collateral Flow in Acute Ischemic Stroke: Rationale and Study Protocol of a Multicenter, Randomized, Proof-of-Concept, Phase 2a/b Trial in Patients Treated With Mechanical Thrombectomy (DOWN-SUITE). Stroke Vasc Interv Neurol. 2026 Feb 4;6(2):e002221. doi: 10.1161/SVIN.125.002221. eCollection 2026 Mar.
- Individual participant dataSharing planned: Yes. The project data can be accessed by interested European and extra-EU third parties for replication or further analysis only if given in a completely anonymous form. Third parties in this project include academic institutions, research centers and non-profit associations (e.g. research consortia). Third parties in this project do not include profit associations (e.g. drug companies).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
BiCRO (academic CRO) contact
Simone Beretta, MD, PhD principal investigator
University of Milano Bicocca
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing HEAD DOWN TILT -10° to -15° in people with Acute Ischemic Stroke, run by University of Milano Bicocca at 6 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Simone Beretta, MD, PhD (+390392333568, simone.beretta@unimib.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Good collateral status (time frame: Day 0 (during mechanical thrombectomy)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06297863, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2026.