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

Phase 2

Completed

• Conditions: Stroke, Acute; Neuroprotection
• Interventions: Drug: Normobaric Hyperoxia; Drug: Sham Normobaric Hyperoxia; Procedure: Endovascular Thrombectomy

• Registration Number: NCT04681651
• Lead Sponsor: Capital Medical University

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-12-06
• Study First Submitted QC: 2020-12-19
• Study First Posted: 2020-12-23
• Study Start: 2021-04-22
• Status Verified: 2023-03
• Primary Completion: 2023-05-05
• Study Completion: 2023-05-05
• Last Update Submitted: 2023-07-04
• Last Update Posted: 2023-07-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 282

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

8. 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NBO group	Normobaric Hyperoxia	Normobaric Hyperoxia combined with endovascular mechanical thrombectomy
NBO group	Endovascular Thrombectomy	Normobaric Hyperoxia combined with endovascular mechanical thrombectomy
Control group	Sham Normobaric Hyperoxia	Inhale air placebo plus endovascular mechanical thrombectomy
Control group	Endovascular Thrombectomy	Inhale air placebo plus endovascular mechanical thrombectomy

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Xuan Wu Hospital，Capital Medical University; 🇨🇳 Beijing, Beijing, China