Head Down Tilt 15° to Increase Collateral Flow in Acute Ischemic Stroke

NCT06297863 | Recruiting Phase 2 DMC

• 1 other identifier: DOWN-SUITE
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 6

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°).

Conditions

Acute Ischemic Stroke

Keywords

Collaterals; Cerebral hemodynamics; Head down positioning

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 0 (during mechanical thrombectomy)

Secondary Outcomes (10)

• Feasibility of HDT15

  Day 0 (in the emergency room and angio suite)

• Delay to thrombectomy

  Day 0 (in the emergency room and angio suite)

• Vomiting

  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)

Study Arms (2)

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.

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.

Interventions

HEAD DOWN TILT -10° to -15° PROCEDURE

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.

HEAD DOWN TILT -10° to -15° (HDT15)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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) \> 35.
• Patients participating in another interventional trial that would interfere with this study.
• Female patients who are pregnant

Sponsors & Collaborators

• University of Milano Bicocca: lead
• Fondazione IRCCS San Gerardo dei Tintori: collaborator
• Azienda Ospedaliero-Universitaria Careggi: collaborator
• Azienda Ospedaliera Universitaria Policlinico "G. Martino": collaborator
• Azienda Ospedaliero Universitaria, Santa Maria della Misericordia di Udine, Italy: collaborator
• Università degli Studi dell'Aquila: collaborator
• Azienda Ospedaliero Universitaria Policlinico Umberto I, Roma: collaborator

Study Sites (6)

Ospedale Civile SS. Nicola e Filippo Avezzano Pronto Soccorso

Avezzano, 67051, Italy

NOT YET RECRUITING

Azienda Ospedaliero Universitaria Careggi

Florence, 50134, Italy

NOT YET RECRUITING

Azienda Ospedaliera Policlinico Universitario "G. Martino"

Messina, 98124, Italy

NOT YET RECRUITING

Fondazione IRCCS San Gerardo dei Tintori Monza

Monza, 20900, Italy

RECRUITING

Azienda Ospedaliero Universitaria Policlinico Umberto I

Roma, 00161, Italy

NOT YET RECRUITING

Ospedale Santa Maria della Misericordia

Udine, 33100, Italy

NOT YET RECRUITING

Related Publications (6)

• 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.

  PMID: 28112023 BACKGROUND

• Diamanti 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.

  PMID: 36300727 BACKGROUND

• Anderson 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.

  PMID: 28636854 BACKGROUND

• Gauthier 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.

  PMID: 30056454 BACKGROUND

• Chen 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.

  PMID: 37147320 BACKGROUND

• Pedrazzini 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.

  PMID: 41815317 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Simone Beretta, MD, PhD

  University of Milano Bicocca

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Simone Beretta, MD, PhD

CONTACT

+390392333568; simone.beretta@unimib.it

BiCRO (academic CRO)

CONTACT

bicro@unimib.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 26, 2024
• First Posted: March 7, 2024
• Study Start: March 1, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: After completion of the primary analysis
• Access Criteria: If the need arises to communicate data in pseudo-anonymous form, the patient will, first of all, be informed and specific informed consent will be provided. In the latter case, the data will not be sent without the patient's consent. Ad hoc Data Transfer Agreements will be established with the interested third parties.

Locations

IT (6)