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

NCT ID: NCT04681651

Last Updated: 2023-07-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 282 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-22
• Study Completion Date: 2023-05-05

Brief Summary

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.

Conditions

Stroke, Acute; Neuroprotection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

NBO group

Normobaric Hyperoxia combined with endovascular mechanical thrombectomy

Group Type: EXPERIMENTAL

Normobaric Hyperoxia

Intervention Type: DRUG

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.

Endovascular Thrombectomy

Intervention Type: PROCEDURE

EVT is the international guidelines for the treatment of acute ischemic stroke with lage vessel occlusion.

Control group

Inhale air placebo plus endovascular mechanical thrombectomy

Group Type: PLACEBO_COMPARATOR

Sham Normobaric Hyperoxia

Intervention Type: DRUG

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%；

Endovascular Thrombectomy

Intervention Type: PROCEDURE

EVT is the international guidelines for the treatment of acute ischemic stroke with lage vessel occlusion.

Interventions

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.

Intervention Type: 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%；

Intervention Type: DRUG

Endovascular Thrombectomy

EVT is the international guidelines for the treatment of acute ischemic stroke with lage vessel occlusion.

Intervention Type: PROCEDURE

Other Intervention Names

NBO; Sham NBO; EVT

Eligibility Criteria

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;

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

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.

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tianjin Huanhu Hospital

OTHER

Sponsor Role: collaborator

Shengli Oilfield Hospital

OTHER

Sponsor Role: collaborator

Beijing Fengtai You'anmen Hospital

UNKNOWN

Sponsor Role: collaborator

Jiujiang University Affiliated Hospital

OTHER_GOV

Sponsor Role: collaborator

Zhangzhou Municipal Hospital of Fujian Province

OTHER

Sponsor Role: collaborator

Baotou Central Hospital

OTHER

Sponsor Role: collaborator

Luoyang Central Hospital

OTHER

Sponsor Role: collaborator

Nanyang Central Hospital

OTHER

Sponsor Role: collaborator

Qingdao Central Hospital

OTHER

Sponsor Role: collaborator

The Third People's Hospital of Jinan

UNKNOWN

Sponsor Role: collaborator

Rizhao People's Hospital

OTHER

Sponsor Role: collaborator

Anyang People's Hospital

UNKNOWN

Sponsor Role: collaborator

Shanghai 10th People's Hospital

OTHER

Sponsor Role: collaborator

Dalian Municipal Central Hospital

OTHER

Sponsor Role: collaborator

Zhoukou Central Hospital

OTHER

Sponsor Role: collaborator

Nanshi Hospital of Nanyang

UNKNOWN

Sponsor Role: collaborator

The second Nanning People's Hospital

UNKNOWN

Sponsor Role: collaborator

Zhumadian Central Hospital

OTHER

Sponsor Role: collaborator

Taizhou Hospital

OTHER

Sponsor Role: collaborator

Second Affiliated Hospital of Nanchang University

OTHER

Sponsor Role: collaborator

Capital Medical University

OTHER

Sponsor Role: lead

Responsible Party

Ji Xunming,MD,PhD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xunming Ji, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Capital Medical University

Locations

Xuan Wu Hospital，Capital Medical University

Beijing, Beijing Municipality, China

Countries

China

References

Li W, Lan J, Wei M, Liu L, Hou C, Qi Z, Li C, Jiao L, Yang Q, Chen W, Liu S, Yue X, Dong Q, Yuan H, Gao Z, Wu X, Wen C, Li T, Jiang C, Li D, Chen Z, Shi J, Shi W, Yuan J, Qin Y, Li B, Fisher M, Feng W, Liu KJ, Ji X; OPENS-2 Investigators. Normobaric hyperoxia combined with endovascular treatment for acute ischaemic stroke in China (OPENS-2 trial): a multicentre, randomised, single-blind, sham-controlled trial. Lancet. 2025 Feb 8;405(10477):486-497. doi: 10.1016/S0140-6736(24)02809-5.

Reference Type: DERIVED

PMID: 39922675 (View on PubMed)

Other Identifiers

OPENS-2

Identifier Type: -

Identifier Source: org_study_id