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CompletedNCT05965687Updated Jul 30, 2026

Normobaric Hyperoxia Combined With Intravenous Thrombolysis for Acute Ischemic Stroke (OPENS-3)

A Phase 3 interventional study of Normobaric Hyperoxia and Nasal oxygen in Acute Ischemic Stroke, sponsored by Ji Xunming,MD,PhD. Completed at 1 site in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-30.

Sponsored by Ji Xunming,MD,PhD · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
1,230
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of this study is to determine the efficacy and safety of Normobaric Hyperoxia combined with intravenous thrombolysis for acute ischemic stroke.

Read the detailed description

In this study, cases of acute ischemic stroke who undergo intravenous thrombolysis within 4.5 hours from onset are included. The Normobaric Hyperoxia(NBO) group receive basic intravenous thrombolysis and given 100% oxygen inhalation at a ventilation rate of 10L/ min using a sealed non-ventilating oxygen storage mask and keep giving oxygen for 4 hours. The control group receive basic intravenous thrombolysis and given oxygen inhalation at a ventilation rate of 1L/min using nasal cannula and keep giving oxygen for 4 hours. The investigators aimed to determine the efficacy and safety of Normobaric Hyperoxia combined with intravenous thrombolysis for acute ischemic stroke.

02

Conditions studied

  • Acute Ischemic Stroke

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03

In context

Ischemic Stroke

2,593 studies on the registry are indexed under Ischemic Stroke; 930 are open to participants now.

This study's enrollment of 1,230 is above the median of 120 across 1,752 interventional studies indexed under Ischemic Stroke.

Browse Ischemic Stroke studies →

Lead sponsor

Ji Xunming,MD,PhD is the lead sponsor of 14 studies on the registry; 3 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Age≥18 years;
  2. The time from onset to randomization is within 4.5 hours of onset;
  3. The clinical diagnosis is acute ischemic stroke (the criteria followed the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2018);
  4. Baseline NIHSS (at the time of randomization) should be ≥5 and ≤25 points;
  5. Pre-stroke mRS score≤1 points;
  6. Informed consent from the patient or surrogate.

Exclusion criteria

Exclusion Criteria:

  1. Intracranial hemorrhage (including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/extradural hematoma, etc.);
  2. Past history of intracranial hemorrhage;
  3. Rapid neurological function improvement, NIHSS score less than 5 points;
  4. Presence of proximal arterial occlusion on computed tomographic angiography(CTA)/magnetic resonance angiography(MRA) (e.g., intracranial internal carotid artery(ICA), middle cerebral artery(MCA)-M1, and vertebrobasilar arteries);
  5. Massive anterior cerebral infarction identified by CT or MRI (ASPECT \< 6 or lesions larger than one third of the territory of the middle cerebral artery);
  6. Intended to proceed endovascular treatment;
  7. Pregnant women, or planning to become pregnant during the trial;
  8. A history of severe head trauma or stroke within 3 months;
  9. A history of intracranial or spinal surgery within 3 months;
  10. A history of gastrointestinal or urinary bleeding within 3 weeks;
  11. two weeks of major surgery;
  12. Arterial puncture was performed at the hemostasis site that was not easily compressed within 1 week;
  13. Active visceral bleeding;
  14. Intracranial tumors, large intracranial aneurysms;
  15. Aortic arch dissection was found;
  16. Severe, sustained hypertension (Systolic Blood Pressure >185 mmHg or Diastolic Blood Pressure >110 mmHg);
  17. Baseline blood glucose of \<50mg/dL (2.78 mmol) or >400mg/dL (22.20 mmol);
  18. Oral warfarin anticoagulant with international normalized ratio(INR)>1.7 or prothrombin time(PT)>15 s;
  19. Heparin treatment was received within 24 h;
  20. Thrombin inhibitors or factor Xa inhibitors were used within 48 h;
  21. Propensity for acute bleeding, including platelet counts of less than 100×109/ L or otherwise;
  22. Hereditary or acquired bleeding constitution;
  23. Onset with seizures;
  24. Severe liver and kidney dysfunction;
  25. Active and chronic obstructive pulmonary disease or acute respiratory distress syndrome;
  26. Patients with anemia or polycythemia vera or other situations that require urgent oxygen inhalation;
  27. Patients with upper gastrointestinal bleeding or nausea or vomiting so that they cannot cooperate with the mask to inhale oxygen;
  28. Life expectancy \< 1 year;
  29. Patients who could not complete the 90-day follow-up;
  30. Participation in other clinical trials within 3 months prior to screening;
  31. Unsuitability or participation in this study as judged by the Investigator may result in subjects being exposed to greater risk.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Outcomes assessor)
Enrollment
1,230 participants (actual)

Study arms

  • Experimental
    NBO group

    Normobaric Hyperoxia combined with intravenous thrombolysis

    Procedure: Normobaric Hyperoxia · Drug: Intravenous thrombolysis(rt-PA)

  • Placebo comparator
    Control group

    Nasal oxygen combined with intravenous thrombolysis

    Procedure: Nasal oxygen · Drug: Intravenous thrombolysis(rt-PA)

Interventions

  • ProcedureNormobaric Hyperoxia

    Within 4.5 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.

  • ProcedureNasal oxygen

    For nasal oxygen group, patients were immediately given oxygen inhalation (no more than 30 minutes after randomization) at a ventilation rate of 1L/min using nasal cannula 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%.

  • DrugIntravenous thrombolysis(rt-PA)

    10% dose of rt-PA (0.9 mg/kg) is given as bolus and the rest given as an infusion over the remaining 1 hour. Maximum dose 90mg.

06

What researchers measure

Primary outcomes

  1. Utility-weighted modified Rankin scale scores

    Utility-weighted modified Rankin scale scores

    Time frame: 90±7 days after randomization

Secondary outcomes

  1. Cerebral infarct volume

    The infarct volume of cerebral infarct is evaluated by MRI

    Time frame: 24-48hours after randomization

  2. modified rankin scale (mRS) score

    Ordinal distribution of mRS at 90±7 days after randomization;mRS score ranges from 0 to 5, and the higher score means a worse outcome

    Time frame: 90±7 days after randomization

  3. Good functional outcome

    Proportion of subjects with modified rankin scale (mRS) 0-2 at 90±7 days after randomization;mRS score ranges from 0 to 5, and the higher score means a worse outcome

    Time frame: 90 ± 7 days after randomization

  4. Proportion of subjects with modified rankin scale (mRS) 0-3

    Proportion of subjects with mRS 0-3 at 90±7 days after randomization;mRS score ranges from 0 to 5, and the higher score means a worse outcome

    Time frame: 90 ± 7 days after randomization

  5. 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

    Time frame: 4 ± 2 hours, 24 ± 6 hours, 72 ± 24 hours, 7 ± 2 days after randomization

  6. The proportion of neurological function improvement

    ≥ 4 point reduction in National Institutes of Health Stroke Scale (NIHSS) score from baseline at 24 ± 6 hours after randomization;NIHSS score ranges from 0 to 42, and higher scores mean a worse outcome

    Time frame: 24 ± 6 hours after randomization

  7. Proportion of subjects with modified rankin scale (mRS) 0-1

    Proportion of subjects with mRS 0-1 at 30±7 days after randomization;mRS score ranges from 0 to 5, and the higher score means a worse outcome

    Time frame: 30 ± 7 days after randomization

  8. Barthel Index (BI)

    The BI is an ordinal disability score of 10 categories (range from 0 to 100, higher values indicate better prognosis)

    Time frame: 30 ± 7 days,90 ± 7 days after randomization

  9. EuroQol five dimensions questionnaire（EQ-5D）

    The score ranges from 0 to 100, with higher scores indicating optimal health

    Time frame: baseline before randomization,7 ± 2 days,30 ± 7 days,90 ± 7 days after randomization

  10. Days of hospitalization

    Length of stay in hospital

    Time frame: 30 ± 7 days after randomization

  11. Stroke-related mortality

    Safety endpoint; the proportion of stroke related deaths in each group

    Time frame: 90 ± 7 days after randomization

  12. All-cause mortality

    Safety endpoint; the proportion of all patients who died in each group

    Time frame: 90 ± 7 days after randomization

  13. Symptomatic intracranial hemorrhage

    Proportion of subjects with symptomatic intracranial hemorrhage at 24 ± 6 hours after randomization (defined by ECASSII and ECASS III)

    Time frame: 24 ± 6 hours after randomization

  14. Asymptomatic intracranial hemorrhage

    The incidence of asymptomatic intracranial hemorrhage at 24 ± 6 hours after randomization

    Time frame: 24 ± 6 hours after randomization

  15. PH2 intracranial hemorrhage

    The incidence of PH2 intracranial hemorrhage at 24 ± 6 hours after randomization (according to SITS standards)

    Time frame: 24 ± 6 hours after randomization

  16. Any intracranial hemorrhage

    The incidence of any intracranial hemorrhage at 24 ± 6 hours after randomization

    Time frame: 24 ± 6 hours after randomization

  17. Systematic bleeding

    The incidence of systematic bleeding at 24 ± 6 hours after randomization

    Time frame: 24 ± 6 hours after randomization

  18. Early neurological deterioration

    Safety endpoint; defined as ≥4 point increase in National Institutes of Health Stroke Scale (NIHSS) score from baseline;NIHSS score ranges from 0 to 42, and higher scores mean a worse outcome

    Time frame: 24 ± 6 hours after randomization

  19. 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

    Time frame: 90 ± 7 days after randomization

  20. Adverse events/serious adverse events

    Safety endpoint; the proportion of adverse events/serious adverse events in each group

    Time frame: 24 ± 12 hours, 7 ± 2 days, 90± 7 days after randomization

  21. PaO2 of arterial blood gas analysis

    Safety endpoint

    Time frame: after 4 hours of oxygen therapy

  22. PaCO2 of arterial blood gas analysis

    Safety endpoint

    Time frame: after 4 hours of oxygen therapy

  23. Potential of hydrogen(PH) of arterial blood gas analysis

    Safety endpoint

    Time frame: after 4 hours of oxygen therapy

  24. Concentration of Lactic acid of arterial blood gas analysis

    Safety endpoint

    Time frame: after 4 hours of oxygen therapy

  25. Systolic and diastolic blood pressure

    Safety endpoint; vital signs

    Time frame: 24 ± 6 hours after randomization

  26. Heart rate

    Safety endpoint; vital signs

    Time frame: 24 ± 6 hours after randomization

  27. Respiratory rate

    Safety endpoint; vital signs

    Time frame: 24 ± 6 hours after randomization

  28. Oxygen saturation

    Safety endpoint; vital signs

    Time frame: 24 ± 6 hours after randomization

  29. Unit costs

    Unit costs will be attached to resource use, patient-reported and from hospital records after randomization, to obtain a cost per patient over the period of follow-up

    Time frame: 7 ± 2 days, 30 ± 7 days,90 ± 7 days after randomization

  30. Excellent functional outcome

    Proportion of subjects with modified Rankin Scale(mRS) 0-1 at 90±7 days after randomization;mRS score ranges from 0 to 5, and the higher score means a worse outcome

    Time frame: 90±7 days after randomization

07

Study locations

1 site
  • Xuan Wu Hospital，Capital Medical University
    Beijing, China
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 30, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT05965687
Lead sponsor
Ji Xunming,MD,PhD
Collaborators
Beijing Friendship Hospital, Beijing Shijitan Hospital, Capital Medical University, Beijing Tongren Hospital, People's Hospital of Beijing Daxing District, Tianjin Huanhu Hospital, Guizhou Provincial People's Hospital, Shandong Provincial Hospital, The First Affiliated Hospital of Soochow University, The First Affiliated Hospital of Zhengzhou University, The Affiliated Hospital of Xuzhou Medical University, Jining First People's Hospital, Linyi People's Hospital, Nanyang Central Hospital, Rizhao People's Hospital, Zhumadian Central Hospital, Second Affiliated Hospital of Nanchang University, Affiliated Hospital of Nantong University, The Second Hospital of Anhui Medical University, Changsha Central Hospital, Jiujiang University Affiliated Hospital, Liaocheng People's Hospital, Chengde Central Hospital, The First Affiliated Hospital of Anhui Medical University, Jiangxi Provincial People's Hopital
Responsible party
Ji Xunming,MD,PhD (Professor, Capital Medical University) — Sponsor-investigator
First posted
Jul 28, 2023
Start date
Aug 17, 2023
Primary completion
Feb 16, 2026
Completion
Feb 16, 2026
Last update
Jul 30, 2026

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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