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ZODIAC

Optimal Head-of-Bed Positioning Before Thrombectomy in Large Vessel Occlusion Stroke: A Randomized Clinical Trial

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Year of Publication: 2025

Authors: Anne W. Alexandrov, Anne J. Shearin, Pitchaiah Mandava, ..., Andrei V. Alexandrov

Journal: JAMA Neurology

Citation: JAMA Neurol. 2025;82(9):905-914. doi:10.1001/jamaneurol.2025.2253

Link: https://doi.org/10.1001/jamaneurol.2025.2253

Clinical Question

Is 0° head positioning superior to 30° head positioning at maintaining clinical stability in patients with large vessel occlusion stroke who are candidates for thrombectomy?

Bottom Line

0° head positioning was superior to 30° positioning for maintaining clinical stability in patients with large vessel occlusion stroke before thrombectomy, with significantly lower rates of neurological deterioration and mortality.

Major Points

  • Prospective randomized clinical trial with outcome blinding conducted at 12 certified thrombectomy hospitals
  • 92 patients randomized to 0° (n=45) or 30° (n=47) head positioning before thrombectomy
  • Primary endpoint was early neurological deterioration (≥2 NIHSS points worsening)
  • Study was terminated early by DSMB at second interim analysis due to efficacy
  • 0° positioning resulted in 34.4-fold lower hazard of clinical worsening compared to 30° positioning
  • Safety profile favored 0° positioning with lower severe deterioration and mortality rates
  • No patients developed hospital-acquired pneumonia in either group

Design

Study Type: Prospective randomized clinical trial

Randomization: 1

Blinding: Outcome-blinded practitioners collected NIHSS measures; emergency physicians, nurses, residents, and neurointerventionalists were not informed of study enrollment

Enrollment Period: May 2018 to November 2023

Follow-up Duration: 3 months

Centers: 12

Countries: United States

Sample Size: 92

Analysis: Intention-to-treat analysis using Cox proportional hazards modeling, Kaplan-Meier curves, Fisher Exact test, logistic regression; statistical analyses performed using R version 4.3.1

Inclusion Criteria

  • Age ≥18 years
  • Baseline head CT negative for hemorrhage or mass effect
  • Alberta Stroke Program Early Computed Tomography Score (ASPECTS) ≥6 for anterior circulation stroke
  • Large vessel occlusion on CT angiography
  • Prestroke baseline modified Rankin Score 0-1
  • Originally within 6 hours of symptom onset, amended to allow up to 24 hours with ASPECTS ≥6 and/or favorable CT perfusion

Exclusion Criteria

  • Systemic thrombolysis given >15 minutes before randomization
  • Vomiting before consent
  • Emergent intubation (thrombectomy procedural intubation allowed)
  • Conditions challenging tolerance of 0° head positioning
  • Known pneumonia, pleural effusion, pulmonary edema, or concerning breath sounds
  • Patients with disabilities lacking legal representative

Arms

FieldControl0° head positioning
InterventionPatients positioned with head elevated to 30° using height-graded electrical or hydraulic stretchers, with investigators maintaining assigned position until thrombectomy commencedPatients positioned with head flat at 0° using height-graded electrical or hydraulic stretchers, with investigators maintaining assigned position until thrombectomy commenced
DurationFrom randomization until movement to catheterization tableFrom randomization until movement to catheterization table

Outcomes

OutcomeTypeControlInterventionHR / OR / RRP-value
Early neurological deterioration (NIHSS worsening ≥2 points) before thrombectomyPrimary26 patients (30° group)1 patient (0° group)34.4<0.001
Severe neurological deterioration (≥4 NIHSS points worsening)Secondary20 patients (30° group)1 patient (0° group)23.570.002
90-day all-cause mortalitySecondary10/46 (21.74%)2/45 (4.44%)5.810.03
Improvement at 24 hoursSecondary28/47 (59.57%)39/45 (86.67%)0.240.01
Improvement at discharge/day 7Secondary31/47 (65.96%)39/45 (86.67%)0.320.03
90-day mRS 0-2Secondary26/46 (56.52%)31/45 (68.89%)0.590.22
Hospital-acquired pneumoniaAdverse00
Death at discharge/day 7Adverse1/47 (2.13%)1/45 (2.22%)0.960.98
Symptomatic intracerebral hemorrhageAdverse1/47 (2.13%)0>0.99

Subgroup Analysis

All 30 patients undergoing thrombectomy in the 0° group achieved eTICI 2b50-3 scores on final angiographic runs, compared with 34 of 39 patients (87.2%) in the 30° group (P = 0.06). At discretion of neurointerventionalists, 15 patients (33.3%) in 0° group and 8 patients (17.0%) in 30° group did not undergo thrombectomy.

Criticisms

  • Small sample size (92 patients) must be considered despite large effect size
  • Study and outcome-blinded practitioners collected NIHSS measures because disguising patient head position was impossible
  • Clinical improvement may have influenced neurointerventionalist decisions not to treat patients in 0° group
  • Patients transferred between facilities were not enrolled due to transport positioning challenges
  • Study was terminated early by DSMB, preventing full enrollment of planned 182 patients

Funding

National Institutes of Health R01 grant 1R01NR017850 from 2018 to 2024

Based on: ZODIAC (JAMA Neurology, 2025)

Authors: Anne W. Alexandrov, Anne J. Shearin, Pitchaiah Mandava, ..., Andrei V. Alexandrov

Citation: JAMA Neurol. 2025;82(9):905-914. doi:10.1001/jamaneurol.2025.2253

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