Oxygen Concentration Target in Stroke Endovascular Treatment (Oxy-TARGET)

Oxygenation Targets for Endovascular Therapy in Acute Ischemic Stroke Patients (Oxy-TARGET)

The goal of this clinical trial is to compare the effects of different concentrations of normobaric oxygen on early neurological improvement in acute ischemic stroke (AIS) patients receiving endovascular therapy (EVT). The main questions it aims to answer are:

• Evaluating the impact of normobaric high-concentration oxygen versus low-concentration oxygen on early neurological function after EVT.
• Evaluating the safety of high and low normobaric oxygen concentration in patients with ischemic stroke.

Participants will (1) receive EVT under general anesthesia; (2) be randomly assigned 1:1 to receive oxygen therapy with FiO2=80% or FiO2=30% through endotracheal intubation during the operation, and the gas flow rate was set at 4L /min.

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke
• Intervention / Treatment: Other: Normobaric high-concentration oxygen; Other: Normobaric low-concentration oxygen

Detailed Description

The optimal fraction of inspired oxygen (FiO2) during EVT under general anesthesia is currently uncertain. This is a randomized controlled trial (RCT) designed to assess the impact of normobaric high-concentration oxygen versus low-concentration oxygen on early neurological function following EVT. It is a prospective, open-label, parallel-design RCT planned to be conducted at Beijing Tiantan Hospital, Capital Medical University. It is anticipated that 200 cases of AIS patients undergoing EVT under general anesthesia will be consecutively enrolled from 2024 to 2026. Eligible participants will be randomly assigned in a 1:1 ratio. After general anesthesia induction, patients will receive continuous inhalation of oxygen with either FiO2=80% or FiO2=30% through endotracheal intubation until the end of the procedure, with a gas flow rate set at 4 L/min. The positive end-expiratory pressure (PEEP) is uniformly set to 5 cmH2O to balance its effect on pulmonary oxygen delivery. The primary outcome will be the occurrence of early neurological improvement (NIHSS score of 10 points 24±2 hours after EVT). Safety outcomes include potential adverse events such as site infection, three-month mortality, etc.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ruquan Han, Ph.D; Phone Number: +86 13701285393; Email: ruquan.han@ccmu.edu.cn
• Study Contact Backup: Name: Zhengfang Hu, M.D; Phone Number: +86 13041084927; Email: huzhengfang78@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100070
      • Recruiting
      • Beijing Tiantan Hospital, Capital Medical University
      • Contact: Ruquan Han, Ph.D; Phone Number: 86-13701285393; Email: ruquan.han@ccmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

1. Age ≥18 years.
2. Anterior circulation occlusive stroke is confirmed by CT angiography (CTA), magnetic resonance angiography (MRA) or digital subtraction angiography (DSA), and occlusions of intracranial internal carotid artery (ICA) or M1 segment of the middle cerebral artery (MCA) were involved.
3. NIHSS score at admission: 6-20.
4. Randomization can be completed within 24 hours after stroke onset.

Exclusion criteria

1. Stroke onset within 6-24 hours with a CT perfusion imaging (CTP)-assessed mismatched area<15 ml.
2. Presence of anemia, defined as hemoglobin levels o below 120 g/L in men and below 110 g/L in women.
3. Pre-stroke modified Rankin scale (mRS) score ≥2.
4. Complicated by severe agitation and seizures.
5. Evidence of intracranial hemorrhage at admission.
6. Presence of chronic obstructive pulmonary disease, asthma, or other respiratory conditions, or requirement for daily supplemental oxygen or mechanical ventilation.
7. Baseline arterial blood gas analysis indicating impaired gas exchange: PaO2 < 60 mmHg on room air, or oxygenation index (PaO2/FiO2) < 300 mmHg with supplemental oxygen.
8. Emergency chest CT reveals significant pulmonary parenchymal infection.
9. An oxygen mask or ventilator must be used before anesthesia to maintain a SpO2≥94%.
10. Loss of airway protective reflex or vomiting aspiration upon admission.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normobaric high-concentration oxygen (NBHO) group; After preoxygenating (FiO2=100%, 6 L/min) with a face mask for 3 min, patients will be sequentially administered intravenous sufentanil 0.2 µg/kg followed by propofol 2 mg/kg. Once the eyelash reflex was absent, all patients received 0.6 mg/kg rocuronium, with an endotracheal tube inserted approximately 90 seconds later. Mechanical ventilation is set to volume-controlled ventilation (VCV) mode, fresh gas flow 4 L/min, tidal volume (Vt) 6-8 ml/kg, respiratory rate (RR) 12-14 breaths/min, and positive end-expiratory pressure (PEEP) 5 cmH2O. End-tidal carbon dioxide (PetCO2) will be continuously monitored, maintaining it between 35-40 mmHg. Based on group allocation, the NBHO group will adjust the FiO2 at 80% throughout the surgery. Anesthesia will be maintained through total intravenous anesthesia, continuously infusing remifentanil 0.05-0.1 µg/kg/min and propofol 4-6 mg/kg/min, with intermittent 10 mg rocuronium as needed.	Other: Normobaric high-concentration oxygen; During endovascular therapy, eligible participants will receive FiO2=80% through endotracheal intubation, with a gas flow rate set at 4 L/min.
Experimental: Normobaric low-concentration oxygen (NBLO) group; After preoxygenating (FiO2=100%, 6 L/min) with a face mask for 3 min, patients will be sequentially administered intravenous sufentanil 0.2 µg/kg followed by propofol 2 mg/kg. Once the eyelash reflex was absent, all patients received 0.6 mg/kg rocuronium, with an endotracheal tube inserted approximately 90 seconds later. Mechanical ventilation is set to volume-controlled ventilation (VCV) mode, fresh gas flow 4 L/min, tidal volume (Vt) 6-8 ml/kg, respiratory rate (RR) 12-14 breaths/min, and positive end-expiratory pressure (PEEP) 5 cmH2O. End-tidal carbon dioxide (PetCO2) will be continuously monitored, maintaining it between 35-40 mmHg. Based on group allocation, the NBLO group will adjust the FiO2 at 30% throughout the surgery. Anesthesia will be maintained through total intravenous anesthesia, continuously infusing remifentanil 0.05-0.1 µg/kg/min and propofol 4-6 mg/kg/min, with intermittent 10 mg rocuronium as needed.	Other: Normobaric low-concentration oxygen; During endovascular therapy, eligible participants will receive FiO2=30% through endotracheal intubation, with a gas flow rate set at 4 L/min.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the incidence of early neurological improvement (ENI)	ENI is defined as an NIHSS score of <10 points at 24±2 hours after EVT	24±2 hours after EVT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
favorable functional outcome	an mRS score of 0-2 at 90 days	90 days after stroke onset
early neurological deterioration (END)	an increase of ≥4 from the baseline NIHSS score on day 1 after reperfusion therapy in AIS patients	1 day after reperfusion therapy
Postoperative pulmonary complications	defined as a composite measure encompassing pulmonary infections, atelectasis, pleural effusion, respiratory failure, bronchospasm, and pneumothorax	within 7 days after endovascular therapy
ΔNIHSS at 24±2 hours after EVT	baseline NIHSS score - NIHSS score at 24±2 h	24±2 hours after EVT
overall mRS distribution at 90 days	modified Rankin scale (mRS) scores are distributed between 0 and 6	90 days after stroke onset
the final infarct volume	After collecting cranial CT images, the infarct volume was delineated using ITK-SNAP software.	72 hours post-randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
stroke-related death	typically defined as death directly attributable to the stroke and its complications, encompassing but not limited to severe cerebral edema, brain herniation, infections, cardiac diseases, pulmonary embolism, and deep vein thrombosis occurring during the acute phase of AIS	within 7 days after endovascular therapy
symptomatic ICH	defined as the presence of hemorrhage on CT at 24±12 h accompanied by an NIHSS score increase≥4	24±12 hours after EVT
all-cause mortality at 90 days	deaths from any cause during the 3-month follow-up period	90 days after stroke onset
Postoperative baseline oxygenation index	oxygenation index=PaCO2/FiO2	From the end of the intervention procedure until the time just before the tracheal tube is removed.
Postoperative baseline PaO2	Arterial partial oxygen pressure based on arterial blood gas	From the end of the intervention procedure until the time just before the tracheal tube is removed.

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Investigators: Study Director: Ruquan Han, Ph.D, Department of Anesthesiology, Beijing TianTan Hospital, Capital Medical University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: December 17, 2023
• First Submitted That Met QC Criteria: January 16, 2024
• First Posted (Actual): January 25, 2024

Study Record Updates

• Last Update Posted (Estimated): December 2, 2024
• Last Update Submitted That Met QC Criteria: November 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Acute ischemic stroke; Normobaric hyperoxia; General anesthesia; Endovascular therapy; Early neurological improvement
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Ischemic Stroke; Stroke; Ischemia
• Other Study ID Numbers: zkd20231121

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No