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

Acute Ischemic Stroke Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05965687
• Other study ID #: OPENS-3
• Status: Recruiting
• Phase: Phase 3
• Start date: August 17, 2023
• Est. completion date: October 30, 2024

Study information

• Verified date: March 2024
• Source: Capital Medical University
• Contact: Xunming Ji, MD. PhD
• Phone: +86010-83199430
• Email: jixm[@]ccmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1230
• Est. completion date: October 30, 2024
• Est. primary completion date: August 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Ischemic Stroke
• Cerebral Infarction
• Hyperoxia
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Procedure:
• Normobaric 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.
• Nasal 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%.

Drug:
• Intravenous 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.

Locations

Country	Name	City	State
China	Xuan Wu Hospital,Capital Medical University	Beijing

Sponsors (25)

Lead Sponsor

Collaborator

Ji Xunming,MD,PhD

Affiliated Hospital of Nantong University, Beijing Friendship Hospital, Beijing Shijitan Hospital, Capital Medical University, Beijing Tongren Hospital, Changsha Central Hospital, Chengde Central Hospital, Guizhou Provincial People's Hospital, Jiangxi Provincial People's Hopital, Jining First People's Hospital, Jiujiang University Affiliated Hospital, Liaocheng People's Hospital, Linyi People's Hospital, Nanyang Central Hospital, People's Hospital of Beijing Daxing District, Rizhao People's Hospital, Second Affiliated Hospital of Nanchang University, Shandong Provincial Hospital, The Affiliated Hospital of Xuzhou Medical University, The First Affiliated Hospital of Anhui Medical University, The First Affiliated Hospital of Soochow University, The First Affiliated Hospital of Zhengzhou University, The Second Hospital of Anhui Medical University, Tianjin Huanhu Hospital, Zhumadian Central Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Utility-weighted modified Rankin scale scores	Utility-weighted modified Rankin scale scores	90±7 days after randomization
Secondary	Cerebral infarct volume	The infarct volume of cerebral infarct is evaluated by MRI	24-48hours after randomization
Secondary	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	90±7 days after randomization
Secondary	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	90 ± 7 days after randomization
Secondary	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	90 ± 7 days after randomization
Secondary	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	4 ± 2 hours, 24 ± 6 hours, 72 ± 24 hours, 7 ± 2 days after randomization
Secondary	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	24 ± 6 hours after randomization
Secondary	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	30 ± 7 days after randomization
Secondary	Barthel Index (BI)	The BI is an ordinal disability score of 10 categories (range from 0 to 100, higher values indicate better prognosis)	30 ± 7 days,90 ± 7 days after randomization
Secondary	EuroQol five dimensions questionnaire(EQ-5D)	The score ranges from 0 to 100, with higher scores indicating optimal health	baseline before randomization,7 ± 2 days,30 ± 7 days,90 ± 7 days after randomization
Secondary	Days of hospitalization	Length of stay in hospital	30 ± 7 days after randomization
Secondary	Stroke-related mortality	Safety endpoint; the proportion of stroke related deaths in each group	90 ± 7 days after randomization
Secondary	All-cause mortality	Safety endpoint; the proportion of all patients who died in each group	90 ± 7 days after randomization
Secondary	Symptomatic intracranial hemorrhage	Proportion of subjects with symptomatic intracranial hemorrhage at 24 ± 6 hours after randomization (defined by ECASSII and ECASS III)	24 ± 6 hours after randomization
Secondary	Asymptomatic intracranial hemorrhage	The incidence of asymptomatic intracranial hemorrhage at 24 ± 6 hours after randomization	24 ± 6 hours after randomization
Secondary	PH2 intracranial hemorrhage	The incidence of PH2 intracranial hemorrhage at 24 ± 6 hours after randomization (according to SITS standards)	24 ± 6 hours after randomization
Secondary	Any intracranial hemorrhage	The incidence of any intracranial hemorrhage at 24 ± 6 hours after randomization	24 ± 6 hours after randomization
Secondary	Systematic bleeding	The incidence of systematic bleeding at 24 ± 6 hours after randomization	24 ± 6 hours after randomization
Secondary	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	24 ± 6 hours after randomization
Secondary	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	90 ± 7 days after randomization
Secondary	Adverse events/serious adverse events	Safety endpoint; the proportion of adverse events/serious adverse events in each group	24 ± 12 hours, 7 ± 2 days, 90± 7 days after randomization
Secondary	PaO2 of arterial blood gas analysis	Safety endpoint	after 4 hours of oxygen therapy
Secondary	PaCO2 of arterial blood gas analysis	Safety endpoint	after 4 hours of oxygen therapy
Secondary	Potential of hydrogen(PH) of arterial blood gas analysis	Safety endpoint	after 4 hours of oxygen therapy
Secondary	Concentration of Lactic acid of arterial blood gas analysis	Safety endpoint	after 4 hours of oxygen therapy
Secondary	Systolic and diastolic blood pressure	Safety endpoint; vital signs	24 ± 6 hours after randomization
Secondary	Heart rate	Safety endpoint; vital signs	24 ± 6 hours after randomization
Secondary	Respiratory rate	Safety endpoint; vital signs	24 ± 6 hours after randomization
Secondary	Oxygen saturation	Safety endpoint; vital signs	24 ± 6 hours after randomization
Secondary	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	7 ± 2 days, 30 ± 7 days,90 ± 7 days after randomization
Secondary	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	90±7 days after randomization