Clinical trial NCT04681651: Normobaric Hyperoxia Combined With Endovascular Treatment in Acute Ischemic Stroke (OPENS-2)
Official title: A Randomized Controlled Trial Assessing the Efficacy and Safety of Normobaric Hyperoxia for Acute Ischemic Stroke Patients Undergoing Endovascular Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stroke, Acute
Neuroprotection
Keywords: Normobaric hyperoxia
Endovascular treatment
Acute ischemic stroke
Lead sponsor: Capital Medical University
Sponsor class: OTHER
Collaborators: name: Tianjin Huanhu Hospital
name: Shengli Oilfield Hospital
name: Beijing Fengtai You'anmen Hospital
name: Jiujiang University Affiliated Hospital
name: Zhangzhou Municipal Hospital of Fujian Province
name: Baotou Central Hospital
name: Luoyang Central Hospital
name: Nanyang Central Hospital
name: Qingdao Central Hospital
name: The Third People's Hospital of Jinan
name: Rizhao People's Hospital
name: Anyang People's Hospital
name: Shanghai 10th People's Hospital
name: Dalian Municipal Central Hospital
name: Zhoukou Central Hospital
name: Nanshi Hospital of Nanyang
name: The second Nanning People's Hospital
name: Zhumadian Central Hospital
name: Taizhou Hospital
name: Second Affiliated Hospital of Nanchang University
First posted: 2020-12-23
Enrollment: 282
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Modified Rankin Scale (mRS) score
timeFrame: 90 ± 14 days after randomization
Secondary outcomes:
measure: Cerebral infarct volume
timeFrame: 24-48h after randomization
measure: The proportion of good prognosis
timeFrame: 90 ± 14 days after randomization
measure: The proportion of functional independence
timeFrame: 90 ± 14 days after randomization
measure: The proportion of severe disability
timeFrame: 90 ± 14 days after randomization
measure: Scores assessed by National Institutes of Health Stroke Scale(NIHSS)
timeFrame: 24 ± 6 hours, 72 ± 24 hours, 7 ± 2 days after randomization
measure: The proportion of neurological function improvement
timeFrame: 24 ± 6 hours after randomization
measure: Successful vessel recanalization
timeFrame: Immediately after procedure
measure: Vessel recanalization
timeFrame: 24 ± 6 hours after randomization
measure: Arterial oxygen partial pressure
timeFrame: after 4 hours of oxygen therapy
measure: Barthel Index (BI)
timeFrame: 90 ± 14 days after randomization
measure: EuroQol five dimensions questionnaire（EQ-5D）
timeFrame: 90 ± 14 days after randomization
measure: Days of hospitalization
timeFrame: 90 ± 14 days after randomization
measure: All-cause mortality
timeFrame: 90 ± 14 days after randomization
measure: Serious adverse events
timeFrame: 90 ± 14 days after randomization
measure: Stroke-related mortality
timeFrame: 90 ± 14 days after randomization
measure: Oxygen-related adverse events
timeFrame: 90 ± 14 days after randomization
measure: Adverse events of special interest
timeFrame: 90 ± 14 days after randomization
measure: Symptomatic intracranial hemorrhage
timeFrame: 24 ± 6 hours after randomization
measure: Any intracranial hemorrhage
timeFrame: 24 ± 6 hours after randomization
measure: Early neurological deterioration (END)
timeFrame: 24 ± 6 hours after randomization
measure: Systolic and diastolic blood pressure
timeFrame: 24 ± 6 hours after randomization
measure: Heart rate
timeFrame: 24 ± 6 hours after randomization
measure: Respiratory rate
timeFrame: 24 ± 6 hours after randomization
measure: Oxygen saturation
timeFrame: 24 ± 6 hours after randomization
measure: PH of arterial blood gas analysis
timeFrame: after 4 hours of oxygen therapy
measure: PaCO2 of arterial blood gas analysis
timeFrame: after 4 hours of oxygen therapy
measure: Lactic acid of arterial blood gas analysis
timeFrame: after 4 hours of oxygen therapy
Other outcomes:
Locations:
city: Beijing
country: China
facility: Xuan Wu Hospital，Capital Medical University
state: Beijing
Study officials:
affiliation: Capital Medical University
name: Xunming Ji, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: