Normobaric Hyperoxia Combined With Endovascular Treatment in Acute Ischemic Stroke (OPENS-2)

A Randomized Controlled Trial Assessing the Efficacy and Safety of Normobaric Hyperoxia for Acute Ischemic Stroke Patients Undergoing Endovascular Treatment

The current endovascular treatment has increased the recanalization rate to more than 90%. Even so, the prognosis rate of stroke is still less than 50%. Our previous research confirmed that the neuroprotective effect of Normobaric Hyperoxia (NBO) from multiple perspectives. However, the clinical study on NBO was not satisfactory, which might be due to the absence of vascular recanalization therapy. Therefore, The investigators conducted this RCT study to further explore the Efficacy and safety of NBO combined with endovascular treatment in patients with acute ischemic stroke.

Study Overview

• Status: Completed
• Conditions: Stroke, Acute; Neuroprotection
• Intervention / Treatment: Drug: Normobaric Hyperoxia; Procedure: Endovascular Thrombectomy; Drug: Sham Normobaric Hyperoxia

• Study Type: Interventional
• Enrollment (Actual): 282
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100069
      • Xuan Wu 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:

General inclusion criteria

1. It conforms to the indications for endovascular thrombectomy
2. 18 ≦ Age ≦ 80 years old.
3. The clinical symptoms and signs are consistent with acute anterior circulation large vessel occlusion; 10≤NIHSS≤20；
4. (Level of consciousness) NIHSS score 0 or 1;
5. The time from onset to randomization is within 6 hours of onset;
6. The mRS score before stroke is 0-1;
7. Patient and family members sign informed consent. Image inclusion criteria

1. Preoperative CT or MR or DSA angiography found large vessel occlusion (internal carotid artery or middle cerebral artery M1 segment) that were consistent with symptoms and signs; 2. ASPECT score ≥ 6 points 3. <1/3 MCA area involvement (confirmed by CT or MRI)

Exclusion Criteria:

• General exclusion criteria

  1. Rapid neurological function improvement, NIHSS score less than 10 points, or evidence of vessel recanalization prior to randomization;
  2. Seizures at stroke onset;
  3. Intracranial hemorrhage;
  4. Symptoms suggestive of subarachnoid hemorrhage, even if CT scan was normal;
  5. Known hemorrhagic diathesis, coagulation factor deficiency, or on anticoagulant therapy with INR > 3.0 or PTT > 3 times normal;
  6. Platelet count of less than 100,000 per cubic millimeter;
  7. Severe hepatic or renal dysfunction;
  8. Severe, sustained hypertension (Systolic Blood Pressure >185 mmHg or Diastolic Blood Pressure >110 mmHg)
  9. Baseline blood glucose of <50mg/dL (2.78 mmol) or >400mg/dL (22.20 mmol)
  10. Active and chronic obstructive pulmonary disease or acute respiratory distress syndrome;
  11. >3 L/min oxygen required to maintain peripheral arterial oxygen saturation (SaO2) 95% as per current stroke management guidelines;
  12. Medically unstable;
  13. Life expectancy<90 days;
  14. Patients who could not complete the 90-day follow-up;
  15. Evidence of intracranial tumor;
  16. Patients with anemia or polycythemia vera or other situations that require urgent oxygen inhalation;
  17. Patients with upper gastrointestinal bleeding or nausea or vomiting so that they cannot cooperate with the mask to inhale oxygen.
  18. A history of severe allergies to contrast agents;
  19. There are any other conditions that are not suitable for endovascular treatment.

Image exclusion criteria

1. CTA/MRAshows excessive bending of blood vessels, which may hinder the delivery of the device;
2. Suspected cerebrovascular inflammation based on medical history and CTA/MRA;
3. Suspected aortic dissection based on medical history and CTA/MRA
4. CTA/MRA confirmed multi-vascular area occlusion (such as bilateral anterior circulation or anterior/posterior circulation), or bilateral infarction or multi- regional infarction;
5. CTA/MRAconfirmed moyamoya disease or moyamoya syndrome;
6. CT/MRI confirmed the obvious effect of midline shift
7. CT/MRI confirmed the presence of intracranial tumors

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: NBO group; Normobaric Hyperoxia combined with endovascular mechanical thrombectomy	Drug: Normobaric Hyperoxia; Within 6 hours after stroke onset, patients were randomized into the NBO group and immediately given 100% oxygen inhalation (no more than 30 minutes after randomization) at a ventilation rate of 10L/ min using a sealed non-ventilating oxygen storage mask and keep giving oxygen for 4 hours. If the patient needs to be intubated with a ventilator to maintain ventilation, the FiO2 should be set to 1.0.; Other Names: NBO; Procedure: Endovascular Thrombectomy; EVT is the international guidelines for the treatment of acute ischemic stroke with lage vessel occlusion.; Other Names: EVT
Placebo Comparator: Control group; Inhale air placebo plus endovascular mechanical thrombectomy	Procedure: Endovascular Thrombectomy; EVT is the international guidelines for the treatment of acute ischemic stroke with lage vessel occlusion.; Other Names: EVT; Drug: Sham Normobaric Hyperoxia; For Sham NBO group, Patients were immediately given oxygen inhalation (no more than 30 minutes after randomization) at a ventilation rate of 1l/min using the same mask and keep giving oxygen for 4 hours. If the patient needs to be intubated with a ventilator to maintain, the FiO2 should be set to 0.3 and gradualy incerased if spO2≤94%； Other Names: Sham NBO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin Scale (mRS) score	the mRs is an ordinal disability score of 7 categories (0=no symptoms to 5=severe disability, and 6=death)	90 ± 14 days after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebral infarct volume	The infarct volume of cerebral infarct is evaluated by MRI or CT	24-48h after randomization
The proportion of good prognosis	defined by mRS 0-2	90 ± 14 days after randomization
The proportion of functional independence	defined by mRS 0-1	90 ± 14 days after randomization
The proportion of severe disability	defined by mRS 4-6	90 ± 14 days after randomization
Scores assessed by National Institutes of Health Stroke Scale(NIHSS)	Scores on the National Institutes of Health Stroke Scale (NIHSS) range from 0 to 42, with higher scores indicating more severe neurologic deficits	24 ± 6 hours, 72 ± 24 hours, 7 ± 2 days after randomization
The proportion of neurological function improvement	≥ 4 point reduction in NIHSS score from baseline	24 ± 6 hours after randomization
Successful vessel recanalization	Successful vessel recanalization is defined by eTICI 2b/2c/3 on final angiogram. Extended treatment in cerebral ischaemia (eTICI) score range from 0 to 3, with higher scores indicating better reperfusion	Immediately after procedure
Vessel recanalization	Vessel recanalization is evaluated by CTA or MRA and assessed by AOL grades. Arterial Occlusive Lesion (AOL) range from 0 to 3, with higher scores indicating better recanalization	24 ± 6 hours after randomization
Arterial oxygen partial pressure	Laboratory indicators, obtained by arterial blood gas analysis	after 4 hours of oxygen therapy
Barthel Index (BI)	the BI is an ordinal disability score of 10 categories (range from 0 to 100, higher values indicate better prognosis)	90 ± 14 days after randomization
EuroQol five dimensions questionnaire（EQ-5D）	The score ranges from 0 to 100, with higher scores indicating optimal health	90 ± 14 days after randomization
Days of hospitalization	Length of stay in hospital	90 ± 14 days after randomization
All-cause mortality	Safety endpoint; the proportion of all patients who died in each group	90 ± 14 days after randomization
Serious adverse events	Safety endpoint; the proportion of serious adverse events in each group	90 ± 14 days after randomization
Stroke-related mortality	Safety endpoint; the proportion of stroke related deaths in each group	90 ± 14 days after randomization
Oxygen-related adverse events	Safety endpoint; the proportion of oxygen-related adverse events in each group, including severe lung infection, pneumothorax, atelectasis, respiratory failure, acute respiratory distress syndrome, and cardiopulmonary arrest	90 ± 14 days after randomization
Adverse events of special interest	Safety endpoint; the proportion of adverse events of special interest in each group, including malignant brain edema, perioperative myocardial infarction, and acute heart failure	90 ± 14 days after randomization
Symptomatic intracranial hemorrhage	Safety endpoint; according to ECASS II definition	24 ± 6 hours after randomization
Any intracranial hemorrhage	Safety endpoint; the proportion of any intracranial hemorrhage in each group	24 ± 6 hours after randomization
Early neurological deterioration (END)	Safety endpoint; defined as ≥4 point increase in NIHSS score from baseline	24 ± 6 hours after randomization
Systolic and diastolic blood pressure	Safety endpoint; vital signs	24 ± 6 hours after randomization
Heart rate	Safety endpoint; vital signs	24 ± 6 hours after randomization
Respiratory rate	Safety endpoint; vital signs	24 ± 6 hours after randomization
Oxygen saturation	Safety endpoint; vital signs	24 ± 6 hours after randomization
PH of arterial blood gas analysis	Safety endpoint	after 4 hours of oxygen therapy
PaCO2 of arterial blood gas analysis	Safety endpoint	after 4 hours of oxygen therapy
Lactic acid of arterial blood gas analysis	Safety endpoint	after 4 hours of oxygen therapy

Collaborators and Investigators

• Sponsor: Capital Medical University
• Collaborators: Shanghai 10th People's Hospital; Second Affiliated Hospital of Nanchang University; Qingdao Central Hospital; Taizhou Hospital; Luoyang Central Hospital; Nanyang Central Hospital; Baotou Central Hospital; Shengli Oilfield Hospital; Tianjin Huanhu Hospital; Nanshi Hospital of Nanyang; Dalian Municipal Central Hospital; Zhangzhou Municipal Hospital of Fujian Province; Zhoukou Central Hospital; Zhumadian Central Hospital; Rizhao People's Hospital; The second Nanning People's Hospital; Beijing Fengtai You'anmen Hospital; Jiujiang University Affiliated Hospital; The Third People's Hospital of Jinan; Anyang People's Hospital
• Investigators: Principal Investigator: Xunming Ji, MD,PhD, Capital Medical University

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2021
• Primary Completion (Actual): May 5, 2023
• Study Completion (Actual): May 5, 2023

Study Registration Dates

• First Submitted: December 6, 2020
• First Submitted That Met QC Criteria: December 19, 2020
• First Posted (Actual): December 23, 2020

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: July 4, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Acute ischemic stroke; Normobaric hyperoxia; 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-2

Drug and device information, study documents

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