Acute Ischemic Stroke
Conditions
Brief summary
The purpose of this study is to determine the efficacy and safety of Normobaric Hyperoxia combined with intravenous thrombolysis for acute ischemic stroke.
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.
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%.
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.
Sponsors
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
Ji Xunming,MD,PhD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Utility-weighted modified Rankin scale scores | 90±7 days after randomization | Utility-weighted modified Rankin scale scores |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| modified rankin scale (mRS) score | 90±7 days after randomization | 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 |
| Good functional outcome | 90 ± 7 days after randomization | 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 |
| Proportion of subjects with modified rankin scale (mRS) 0-3 | 90 ± 7 days after randomization | 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 |
| Scores assessed by National Institutes of Health Stroke Scale(NIHSS) | 4 ± 2 hours, 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 |
| The proportion of neurological function improvement | 24 ± 6 hours after randomization | ≥ 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 |
| Proportion of subjects with modified rankin scale (mRS) 0-1 | 30 ± 7 days after randomization | 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 |
| Barthel Index (BI) | 30 ± 7 days,90 ± 7 days after randomization | The BI is an ordinal disability score of 10 categories (range from 0 to 100, higher values indicate better prognosis) |
| EuroQol five dimensions questionnaire（EQ-5D） | baseline before randomization,7 ± 2 days,30 ± 7 days,90 ± 7 days after randomization | The score ranges from 0 to 100, with higher scores indicating optimal health |
| Days of hospitalization | 30 ± 7 days after randomization | Length of stay in hospital |
| Stroke-related mortality | 90 ± 7 days after randomization | Safety endpoint; the proportion of stroke related deaths in each group |
| All-cause mortality | 90 ± 7 days after randomization | Safety endpoint; the proportion of all patients who died in each group |
| Symptomatic intracranial hemorrhage | 24 ± 6 hours after randomization | Proportion of subjects with symptomatic intracranial hemorrhage at 24 ± 6 hours after randomization (defined by ECASSII and ECASS III) |
| Asymptomatic intracranial hemorrhage | 24 ± 6 hours after randomization | The incidence of asymptomatic intracranial hemorrhage at 24 ± 6 hours after randomization |
| PH2 intracranial hemorrhage | 24 ± 6 hours after randomization | The incidence of PH2 intracranial hemorrhage at 24 ± 6 hours after randomization (according to SITS standards) |
| Cerebral infarct volume | 24-48hours after randomization | The infarct volume of cerebral infarct is evaluated by MRI |
| Systematic bleeding | 24 ± 6 hours after randomization | The incidence of systematic bleeding at 24 ± 6 hours after randomization |
| Early neurological deterioration | 24 ± 6 hours after randomization | 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 |
| Oxygen-related adverse events | 90 ± 7 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/serious adverse events | 24 ± 12 hours, 7 ± 2 days, 90± 7 days after randomization | Safety endpoint; the proportion of adverse events/serious adverse events in each group |
| PaO2 of arterial blood gas analysis | after 4 hours of oxygen therapy | Safety endpoint |
| PaCO2 of arterial blood gas analysis | after 4 hours of oxygen therapy | Safety endpoint |
| Potential of hydrogen(PH) of arterial blood gas analysis | after 4 hours of oxygen therapy | Safety endpoint |
| Concentration of Lactic acid of arterial blood gas analysis | after 4 hours of oxygen therapy | Safety endpoint |
| Systolic and diastolic blood pressure | 24 ± 6 hours after randomization | Safety endpoint; vital signs |
| Heart rate | 24 ± 6 hours after randomization | Safety endpoint; vital signs |
| Respiratory rate | 24 ± 6 hours after randomization | Safety endpoint; vital signs |
| Oxygen saturation | 24 ± 6 hours after randomization | Safety endpoint; vital signs |
| Unit costs | 7 ± 2 days, 30 ± 7 days,90 ± 7 days after randomization | 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 |
| Excellent functional outcome | 90±7 days after randomization | 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 |
| Any intracranial hemorrhage | 24 ± 6 hours after randomization | The incidence of any intracranial hemorrhage at 24 ± 6 hours after randomization |
Countries
China
Contacts
Primary ContactXunming Ji, MD. PhD
Backup ContactHetao Bian, MD.PhD
Outcome results
None listed