ZODIAC trial demonstrates the impact of head-of-bed positioning in LVO stroke care

The ZODIAC study assessed whether maintaining a 0-degree head-of-bed (HOB) position, as opposed to an elevated 30-degree HOB position, enhances clinical stability in patients with a hyperacute large vessel occlusion (LVO) during the pre-thrombectomy period. The trial results presented at the International Stroke Conference (ISC) 2024 demonstrate significant improvements in neurological function for patients with 0-degree compared to 30-degree HOB positioning. ZODIAC stands as the first positive clinical trial investigating the impact of head positioning in thrombectomy candidates, prompting a reevaluation of existing protocols in LVO patient care.

Acute ischemic stroke (AIS) due to large vessel occlusion (LVO) involves a blockage of the large, proximal cerebral arteries. A large body of evidence supports the use of endovascular thrombectomy in eligible patients with LVO stroke, up to 24 hours after stroke onset. It has been repeatedly shown that patient benefits from thrombectomy depend on timing, with time-to-treatment strongly associated with functional outcomes. However, procedural delays are common and thus, managing patients during the pre-thrombectomy window is crucial, emphasizing the need to optimize care for enhanced blood flow to the brain.

The ZODIAC study (NCT03728738), a prospective, randomized, outcome-blinded evaluation (PROBE) clinical trial, sought to identify optimal pre-thrombectomy conditions to enhance blood flow, thereby improving surgical outcomes and reducing the risk of neurological deficits and disability for patients.1

The positioning of the head of the bed (HOB) is a crucial yet understudied factor in the treatment of LVO stroke, directly influencing cerebral blood flow. Clinical studies have documented symptom worsening in patients with AIS when the HOB is elevated to 30 degrees or higher (the current standard), while clinical improvement has been observed with 0-degree HOB positioning.2-4 The positive effects of the latter may be attributed to favorable gravitational blood flow conditions and the recruitment of collateral blood channels, aiding in the transport of thrombolytic medication to facilitate clot breakdown in the brain.5 This challenges a historical divide in the clinical community, where a 30-degree HOB position was conventionally believed to manage intracranial pressure in neurological diagnoses, prompting a reevaluation of these practices.6

“Putting the head down at zero degrees increases the cerebral blood flow by 20%” -Anne W Alexandrov, PhD, RN, CCRN, ANVP-BC, NVRN-BC, FAAN, University of Tennessee Health Science Center and ZODIAC study leader.

The ZODIAC trial included 92 patients from 12 US hospitals with confirmed LVO who were eligible for thrombectomy based on the presence of viable brain tissue.1 Despite the initial plan to include a larger sample, the trial’s robust findings at a planned interim analysis led the Data and Safety Monitoring Board (DSMB) to halt further enrollment. Patients were randomly assigned to either a 0-degree or 30-degree HOB position. To assess neurological function, National Institutes of Health Stroke Scale (NIHSS) scores were calculated immediately after neuroimaging and every 10-minutes thereafter until thrombectomy. The primary endpoint was early neurological deterioration defined as an increase of at least 2 points on the NIHSS before thrombectomy.6

The interim analysis found that positioning patients at 0-degrees HOB resulted in greater clinical stability and/or clinical improvement compared to an elevated HOB. At at a 30-degree HOB, 55% of patients exhibited an increase of ≥2 points on NIHSS, versus 2% in the 0-degree HOB arm (HR 50.5, p<0.001). Furthermore, at a 30-degree HOB, 43% of individuals exhibited an NIHSS deterioration ≥4 points, in contrast to 2% observed in the 0-degree HOB group (HR 32.6, p<0.001).6 This indicates that approximately 1 in 2 patients in the 30-degree group had a decline in neurological function during the pre-thrombectomy period.

In addition, when assessing exploratory endpoints, including 24-hour and 7-day/discharge NIHSS scores, the researchers were surprised to find that a higher percentage of patients in a 0-degree HOB position before surgery had improved NIHSS scores at 24-hours (87% vs 61%; p=0.007) and 7-days (87% vs 67%; p=0.03), compared to the 30-degree group.6 In this way, a 0-degree HOB position not only enhanced clinical stability before treatment but also resulted in improved neurological outcomes in the immediate post-treatment period.

As discussed in an interview with Prof. Anne Alexandrov, the results of the ZODIAC trial represent a significant advancement in managing patients with LVO during the pre-thrombectomy period, which she anticipates will prompt a reevaluation of historic practices.7

“Zero-degree head positioning is a safe and effective strategy to optimize blood flow to the brain until the thrombectomy can be performed, and it should be considered the standard of care for stroke patients prior to thrombectomy.” -Anne W Alexandrov, PhD, RN, CCRN, ANVP-BC, NVRN-BC, FAAN, University of Tennessee Health Science Center and ZODIAC study leader.

Prof. Alexandrov proposes exploring post-thrombectomy studies to determine optimal patient positioning, and emphasizes the need for extensive implementation efforts.6 In addition, Prof. Alexandrov is conducting preliminary studies to explore the impact of bed positioning on NIHSS in patients with intracerebral hemorrhage (ICH) before initiating a trial.8

Written by Mary Kelly

Reviewed by Emma Williams


  1. Alexandrov AW. Zero Degree Head Positioning in Hyperacute Large Artery Ischemic Stroke (ZODIAC). ClinicalTrials.gov. [Accessed Feb 2024].
  2. Meixensberger J, Baunach S, Amschler J, et al. Influence of body position on tissue pO2, cerebral perfusion pressure and intracranial pressure in patients with acute brain injury. Neurol Res. Jun 1997;19: 249 –253.
  3. Winkelman C. Effect of backrest position on intracranial and cerebral perfusion pressures in traumatically brain-injured adults. Am J Crit Care. Nov 2000;9:373–380.
  4. Moraine JJ, Berre J, Melot C. Is cerebral perfusion pressure a major determinant of cerebral blood flow during head elevation in comatose patients with severe intracranial lesions? J Neurosurg. Apr 2000;92:606 – 614.
  5. American Heart Association. Position of stroke patient’s head before surgery may improve neurological function [Press Release]. Feb 2024. [Accessed 20 Feb. 2024].
  6. Alexandrov AW. Zero Degree Head Positioning in Acute Large Vessel Ischemic Stroke. Presented at the International Stroke Conference 2024; 7 Feb 2024; Arizona, US.
  7. Alexandrov AW. ZODIAC trial results: conclusive evidence for head positioning in stroke care. [Interview with VJNeurology]. Feb 2024
  8. Alexandrov AW. Potential impact of head positioning in intracerebral hemorrhage. [Interview with VJNeurology]. Feb 2024