Normobaric Hyperoxia Combined With Reperfusion for Acute Ischemic Stroke

The Safety and Efficacy of Normobaric Hyperoxia Combined With Reperfusion for Acute Ischemic Stroke：A Randomized, Controlled Pilot Study

NBO is a nonpharmacological measure of neuroprotection. The purpose of our study is to evaluate the safety and efficiency of NBO（Normobaric hyperoxia) in the acute ischemic stroke patients who received endovascular treatment. Looking for more clinical evidence for the ischemic stroke patients who will be treated with NBO in the future.

Study Overview

• Status: Completed
• Conditions: Stroke, Acute
• Intervention / Treatment: Drug: Normobaric oxygen therapy

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijin, China
    • Xuanwu hospital;Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female, age≥18 and ≤ 80;
• Suspected lage vessel occlusion of acute anterior circulation occlusion; i.e. either the ICA or the M1-segment of the MCA;
• Acute ischemic stroke where patient is ineligible for intravenous thrombolytic treatment or the treatment is contraindicated, or where patient has received intravenous thrombolytic therapy without recanalization;
• Patient treatable within 6 hours of symptom onset;or it has been more than 6 hours but not more than 24 hours,and imaging confirmed the existence of ischemic penumbra;
• NIHSS score≥6分
• Alberta Stroke Program Early CT score (ASPECTS) of 7-10 on non-contrast CT;
• Informed consent obtained;

Exclusion Criteria:

• Rapid improvement in neurological status to an NIHSS < 6 or evidence of vessel recanalization prior to randomization;
• Seizures at stroke onset;
• Intracranial hemorrhage;
• Systolic pressure greater than 185 mm Hg or diastolic pressure greater than 110 mm Hg, or aggressive treatment intravenous medication)necessary to reduce blood pressure to these limits;
• Symptoms rapidly improving;
• Symptoms suggestive of subarachnoid hemorrhage, even if CT scan was normal;
• Platelet count of less than 100,000 per cubic millimeter;
• CT showed a multiple infarction (low density area greater than 1/3 cerebral hemisphere);
• severe hepatic or renal dysfunction;
• 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;
• inability to obtain informed consent;
• Life expectancy<90 days;
• Pregnant or breast-feeding women;
• Unwilling to be followed up or poor compliance for treatment;
• Patients being enrolled or having been enrolled in other clinical trial within 3 months prior to this clinical trial;
• Evidence of intracranial tumor;
• Baseline blood glucose of < 50 mg/dL (2.78 mmol) or > 400 mg/dL (22.20 mmol);

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NBO group; Normobaric oxygen therapy is the delivery of high-flow oxygen (10L/min) via oxygen storage facemask. This therapy should start in the pre-hospital or emergency room as soon as possible (within 1 hours) after diagnosis of ischemic stroke and last for 4 hours. All participant will receive mechanical thrombectomy and a standard clinical therapy.	Drug: Normobaric oxygen therapy; In this study, it is simple to administer via oxygen storage facemask at flow rates of 10 L/min for 4 hours. This therapy start should in Pre-hospital or emergency room as early as possible after diagnosed ischemic stroke and uninterrupted during other treatments including mechanical thrombolytic therapy and standard clinical treatment.
No Intervention: Control group; The participants receive mechanical thrombectomy therapy after diagnosed ischemic. All participants receive a standard clinical therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebral infarct volume	Infarct volume is evaluated mainly through brain MRI(DWI)	24-48h after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
levels of blood biomarkers	Biomarkers for evaluation of BBB damage and brain injury:NSE、S100B、occludin、 claudin-5、MMP-9	baseline; 24 ± 6 hours, 7 ± 2 days
modified Rankin Scale score (mRS)	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 ± 5 days, 90 ± 10 days after randomization
The good prognosis at 90 days assessed by modified Rankin scale (mRS).	secondary clinical efficacy endpoint;the mRs is an ordinal disability score of 7 categories (0 = no symptoms to 5 = severe disability, and 6 = death);The ratio of 0 to 2;	90 ± 10 days after randomization
Scores assessed by National Institutes of Health Stroke Scale(NIHSS)	secondary clinical efficacy endpoint; the NIHSS is a stroke severity score that is composed of 11 items; range from 0 to 42, higher values indicate more severe deficits	2 hours ± 15 minutes, 24 ± 6 hours, 7 ± 2 days, 30 ± 5 days after randomization ]
Change in National Institutes of Health Stroke Scale (NIHSS) score from baseline to 24 hours	secondary clinical efficacy endpoint;the NIHSS is a stroke severity score composed of 11 items (range from 0 to 42, higher values indicate more severe deficits)	from baseline to 24 ± 6 hours
Improvement of neurologic function after 24h	NIHSS score decreased by more than 4 points or NIHSS score was 0;secondary clinical efficacy endpoint;the NIHSS is a stroke severity score composed of 11 items (range from 0 to 42, higher values indicate more severe deficits)	24 ± 6 hours;
Barthel Index (BI)	secondary clinical efficacy endpoint;the BI is an ordinal disability score of 10 categories(range from 0 to 100, higher values indicate better prognosis);	30 ± 5 days, 90 ± 10 days after randomization
Revascularization on 24-hour follow-up imaging	secondary imaging efficacy endpoint;	24 (12 to 36) hours;
24-hour 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;
any intracranial hemorrhage on 24-hour follow-up imaging	imaging safety endpoints;per ECASS III definition and per Heidelberg bleeding classification	24 (12 to 36) hours
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 to 36) hours
Mortality and Stroke recurrence	clinical safety endpoint;	90 ± 10 days after randomization
Survival rates	secondary clinical efficacy endpoint;	7 ± 2 days, 90 ± 10 days after randomization
TICI (Thrombolysis in Cerebral Infarction perfusion scale grade)	secondary imaging efficacy endpoint;	Time Frame: 4 hours ± 15 minutes
The infarct volume on 24-hour follow-up imaging	The infarct volume of cerebral infarct is evaluated by cranial CT;	24 (12 to 36) hours;
mRS4-6	secondary clinical efficacy endpoint;the mRs is an ordinal disability score of 7 categories (0 = no symptoms to 5 = severe disability, and 6 = death)	90 ± 10 days after randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subgroup analysis of infarct volume	Stratify according to different risk factors：ASPECT; NIHSS; age;Ischemic penumbra volume; Site of occlusion; Time from stroke onset to randomization;Ischemic penumbra volume	24-48h after randomization

Collaborators and Investigators

• Sponsor: Capital Medical University

Publications and helpful links

General Publications

• Li W, Qi Z, Ma Q, Ding J, Wu C, Song H, Yang Q, Duan J, Liu L, Kang H, Wu L, Ji K, Zhao W, Li C, Sun C, Li N, Fisher M, Ji X, Liu KJ. Normobaric Hyperoxia Combined With Endovascular Treatment for Patients With Acute Ischemic Stroke: A Randomized Controlled Clinical Trial. Neurology. 2022 Aug 23;99(8):e824-e834. doi: 10.1212/WNL.0000000000200775. Epub 2022 Jun 17. Erratum In: Neurology. 2023 Apr 25;100(17):844.

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2018
• Primary Completion (Actual): July 21, 2019
• Study Completion (Actual): October 19, 2019

Study Registration Dates

• First Submitted: August 3, 2018
• First Submitted That Met QC Criteria: August 7, 2018
• First Posted (Actual): August 8, 2018

Study Record Updates

• Last Update Posted (Actual): July 19, 2023
• Last Update Submitted That Met QC Criteria: July 18, 2023
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: reperfusion therapy; Normobaric hyperoxia;; Acute ischemic stroke;; vascular recanalization;; Endovascular treatment
• 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: OPENS-1

Drug and device information, study documents

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