Treatment Duration on Normobaric Hyperoxia in Acute Ischemic Stroke

The Efficacy and Safety of Normobaric Hyperoxia on Treatment Duration for Acute Ischemic Stroke Patients With Endovascular Treatment

Normoxia Hyperoxia (NBO) is a neuroprotective approach that can be implemented early. NBO is simple and non-invasive and can be used at home or in an ambulance to ensure the shortest possible time after cerebral ischemia occurs. The previous study by the investigators suggested that NBO therapy in the early stage of cerebral ischemia has a neuroprotective effect on ischemic brain injury. Although the neuroprotective effect of NBO has been demonstrated, the optimal duration of treatment for NBO to exert neuroprotective effect is still unclear. Therefore, further discussion of the duration of NBO treatment will contribute to the clinical application of NBO and provide a definite theoretical basis for the treatment of cerebral infarction.

Study Overview

• Status: Completed
• Conditions: Stroke, Acute; Endovascular Treatment; Neuroprotection
• Intervention / Treatment: Other: Low flow oxygen; Other: Normobaric Hyperoxia (NBO)

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xunming Ji, MD; Phone Number: +86-10-83198952; Email: jixm@ccmu.edu.cn

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Huanhu Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Symptoms and signs were consistent with acute anterior circulation stroke,
• NIHSS score≥6分;Alberta Stroke Program Early CT score (ASPECTS)≥6;
• Met the indications for endovascular therapy;
• (Level of consciousness)NIHSS score 0 or 1; MRS score was 0-1 before stroke
• The time from onset to randomization was within 24 hours;
• Preoperative CTA or MRA confirmed the presence of large vessel occlusion (internal carotid artery or middle cerebral artery M1, M2 segments);
• Patients and their families signed informed consent

Exclusion Criteria:

• Rapid neurological function improvement, NIHSS score less than 10 points, or evidence of vessel recanalization prior to randomization;
• Seizures at stroke onset;
• Intracranial hemorrhage;
• Symptoms suggestive of subarachnoid hemorrhage, even if CT scan was normal;
• Known hemorrhagic diathesis, coagulation factor deficiency, or on anticoagulant therapy with INR > 3.0 or PTT > 3 times normal;
• Platelet count of less than 100,000 per cubic millimeter;
• Severe hepatic or renal dysfunction;
• Severe, sustained hypertension (Systolic Blood Pressure >185 mmHg or Diastolic Blood Pressure >110 mmHg)
• Baseline blood glucose of <50mg/dL (2.78 mmol) or >400mg/dL (22.20 mmol) Active and chronic obstructive pulmonary disease or acute respiratory distress syndrome;
• >3 L/min oxygen required to maintain peripheral arterial oxygen saturation (SaO2) 95% as per current stroke management guidelines;
• Medically unstable;
• Life expectancy<90 days;
• Patients who could not complete the 90-day follow-up;
• Evidence of intracranial tumor;
• Patients with anemia or polycythemia vera or other situations that require urgent oxygen inhalation;
• Patients with upper gastrointestinal bleeding or nausea or vomiting so that they cannot cooperate with the mask to inhale oxygen.
• A history of severe allergies to contrast agents;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Low flow oxygen group; patients were randomized into the Low flow oxygen group and immediately given 100% oxygen inhalation (no more than 30 minutes after admission) at a ventilation rate of 1L/ min using a oxygen storage mask and keep giving oxygen for 4 hours.	Other: Low flow oxygen; immediately given oxygen inhalation at a ventilation rate of 1L/ min using a oxygen storage mask and keep giving oxygen for 4 hours.
Experimental: NBO group (2h); patients were randomized into the NBO group (2h) and immediately given 100% oxygen inhalation (no more than 30 minutes after admission) at a ventilation rate of 10L/ min using a oxygen storage mask and keep giving oxygen for 2 hours.	Other: Normobaric Hyperoxia (NBO); NBO was inhaled as early as possible before revascularization, and inhaled for 1h/2h/4h according to different groups
Experimental: NBO group (4h); patients were randomized into the NBO group (4h) and immediately given 100% oxygen inhalation (no more than 30 minutes after admission) at a ventilation rate of 10L/ min using a oxygen storage mask and keep giving oxygen for 4 hours.	Other: Normobaric Hyperoxia (NBO); NBO was inhaled as early as possible before revascularization, and inhaled for 1h/2h/4h according to different groups
Experimental: NBO group (6h); patients were randomized into the NBO group (6h) and immediately given 100% oxygen inhalation (no more than 30 minutes after admission) at a ventilation rate of 10L/ min using a oxygen storage mask and keep giving oxygen for 6 hours.	Other: Normobaric Hyperoxia (NBO); NBO was inhaled as early as possible before revascularization, and inhaled for 1h/2h/4h according to different groups

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebral infarct volume	The infarct volume is evaluated by MRI or CT scan	Within 72 hours after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Scores assessed by National Institutes of Health Stroke Scale(NIHSS)	secondary clinical efficacy endpoint; the NIHSS is a stroke severity score composed of 11 items (range from 0 to 41, higher values indicate more severe deficits)	24hours, 72hours, day7 after randomization
The proportion of good prognosis	the mRs is an ordinal disability score of 7 categories (0 = no symptoms to 5 = severe disability, and 6 = death;with higher scores indicating more severe disability);The ratio of 0 to 2;	90 ± 10 days after randomization
neurological function improvement rate	NIHSS score increased by more than 4 points);the NIHSS is a stroke severity score composed of 11 items (range from 0 to 42, higher values indicate more severe deficits);	Time Frame: 24 ± 6 hours
modified Rankin Scale score (mRS) score	secondary clinical efficacy endpoint; the mRs is an ordinal disability score of 7 categories (0=no symptoms to 5=severe disability,and 6=death)	30 ± 7 days, 90 ± 10 days after randomization;
Vascular recanalization rate	secondary imaging efficacy endpoint; Extended Treatment In Cerebral Ischemia (eTICI)；The eTICI is an ordinal hierarchical scale ranging from 0 to 3, with higher scores indicating better antegrade reperfusion of the previously occluded target artery ischemic territory; eTICI 2B or 3 are defined as successful recanalization;	Time Frame: 4 hours ± 15 minutes
blood biomarkers : occludin(ng/ml), MMP-9(ng/ml), S100B(ng/ml),NSE(ng/ml),GFAP(ng/ml),PGP9.5(ng/ml),etc	Biomarkers for evaluation of BBB damage , brain injury and inflammation,etc:	24 ± 6 hours, 72 ± 24 hours
Incidence of oxygen-related adverse events	Including Headache, dizziness, nausea, vomiting, chest tightness, shortness of breath, cough,etc;	24 ± 6 hours,
Incidence of neurologic deterioration;	NIHSS score increased by more than 4 points);the NIHSS is a stroke severity score composed of 11 items (range from 0 to 42, higher values indicate more severe deficits);clinical safety endpoint;	24 ± 6 hours;
Incidence of Symptomatic Intracerebral Hemorrhage	imaging safety endpoints;Deterioration in NIHSS score of ≥4 points within 24 hours;per ECASS III definition and per Heidelberg bleeding classification	24± 12 hours hours after randomization
Incidence of any intracranial hemorrhage	imaging safety endpoints;per ECASS III definition and per Heidelberg bleeding classification	24± 12 hours hours after randomization
all-cause death rate	clinical safety endpoint; Ratio of total deaths from all causes to all enrollments	90 ± 10 days after randomization
Incidence of adverse events	clinical safety endpoint;	90 ± 10 days after randomization
Incidence of surgery-related complications	clinical safety endpoint;	24± 12 hours hours after randomization
stroke related death rate	clinical safety endpoint; Stroke-related deaths as a proportion of all participants	90 ± 10 days after randomization;
Vital signs:respiration(times/min)	clinical safety endpoint;	0 hours, 2 hours, 4 hours after randomization;
Vital signs:heart rate: (times/min)	clinical safety endpoint;	0 hours, 2 hours, 4 hours after randomization;
Vital signs:blood pressure(mmHg)	clinical safety endpoint;	0 hours, 2 hours, 4 hours after randomization;
Vital signs:oxygen saturation (%)	clinical safety endpoint;	0 hours, 2 hours, 4 hours after randomization;

Collaborators and Investigators

• Sponsor: Capital Medical University
• Collaborators: Tianjin Huanhu Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2022
• Primary Completion (Actual): September 30, 2023
• Study Completion (Actual): September 30, 2023

Study Registration Dates

• First Submitted: May 24, 2022
• First Submitted That Met QC Criteria: June 1, 2022
• First Posted (Actual): June 3, 2022

Study Record Updates

• Last Update Posted (Actual): December 6, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms, Respiratory; Stroke; Ischemic Stroke; Hyperoxia
• Other Study ID Numbers: TD-NBO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No