A Study of r-PA Treating Patients With Acute Ischemic Stroke（RAISE）

Acute Ischemic Stroke Clinical Trial

Official title:

A Phase III, Multicenter, Randomized, Blind Endpoint and Positive Drug Control Study of Recombinant Human Tissue Plasminogen Kinase Derivatives for Injection in the Treatment of Patients With Acute Ischemic Stroke

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05295173
• Other study ID #: CRAD-001-03
• Status: Completed
• Phase: Phase 3
• Start date: March 21, 2022
• Est. completion date: June 22, 2023

Study information

• Verified date: March 2024
• Source: Angde Biotech Pharmaceutical Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the efficacy and safety of recombinant human tissue plasminogen kinase derivatives for injection and alteplase in the treatment of patients with acute ischemic stroke within 4.5 hours.

Description:

This study is a multicenter, randomized, blind endpoint and positive drug control study. The study plans to recruit 1412 AIS patients within 4.5 hours of onset. Qualified subjects are assigned to the test drug and control drug alteplase group according to the ratio of 1:1. After receiving thrombolytic drugs, the subjects need to carry out a series of safety and effectiveness tests. The mRS score and Barthel index score visits are carried out on the 90th day (± 7 days) after thrombolysis. After the visit, the subjects can leave the group. In this study, independent blind endpoint evaluators were set up in each research center to evaluate the mRS and Barthel index score 30 and 90 days after thrombolysis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1412
• Est. completion date: June 22, 2023
• Est. primary completion date: June 22, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Aged 18 to 80 years(including the critical value);

2. Acute ischemic stroke is diagnosed according to the WHO (World Health Organization) stroke diagnostic criteria, the symptoms of acute ischemic stroke are expected to be less than 4.5 hours after the time of acute ischemic stroke which is defined as the last time the patient functions well;

3. NIHSS score at the time of treatment: from 4 points to 25 points (including 4 points and 25 points);

4. From the signing of informed consent form to 3 months after treatment, fertile men and women of childbearing age should be absent of a birth plan and willing to take effective contraceptive measures;

5. Participants who can understand and follow the research process, voluntarily participate, and sign an informed consent form (informed consent is voluntarily signed by the person or legal representative).

Exclusion Criteria:

1. Known to be allergic to research drugs or similar ingredients, or materials used in imaging studies;

2. Weight >120kg or <45kg;

3. The timing of stroke symptoms is not known;

4. mRS score before stroke= 2 points;

5. NIHSS score 1a (level of consciousness) = 2 points during screening;

6. Patients with intracerebral hemorrhage history;

7. CT/MRI imaging examination shows signs of intracranial hemorrhage or suspected subarachnoid hemorrhage despite CT/MRI imaging findings do not show abnormalities;

8. Severe cerebral trauma or stroke history or other severe traumas within 3 months;

9. Assessment of Intracranial tumor, arteriovenous malformation and aneurysm before admission;

10. Intracranial surgery, intraspinal surgery or other major surgeries within 3 months (based on the assessment of the investigators);

11. Patients with gastrointestinal or urinary system hemorrhage in recent 3 weeks;

12. Active visceral hemorrhage;

13. Assessment or with history of aortic arch dissection before admission;

14. Arterial puncture in 1 week which can not be oppressed;

15. Subjects who have an acute bleeding tendency, including but not limited to:1) a platelet count of less than 100 × 109 / L;2) application of low molecular heparin within 24 hours before onset ; 3) Using of thrombin inhibitors or factor Xa inhibitor within 48 hours before onset ; 4) application of oral anticoagulant drugs and with an INR > 1.7 or PT>15s;

16. Hypertension remains uncontrolled after active antihypertensive therapy, uncontrolled hypertension refers to a systolic blood pressure >185 mmHg and/or a diastolic blood pressure >110 mmHg;

17. Blood glucose <50 mg/dl (equivalent to 2.78mmol/L) or >400 mg/dl (equivalent to 22.2mmol/L);

18. Imaging (CT or MRI)shows large area cerebral infarction;

19. Severe liver damage, including liver failure, cirrhosis, portal hypertension (esophageal varices), and active hepatitis;

20. Bacterial endocarditis or pericarditis, acute pancreatitis at admission;

21. With history of gastrointestinal ulcers, esophageal varices, aneurysms, or arterial / venous malformations within 3 months before admission;

22. Patients who are unable to cooperate or are unwilling to cooperate with epileptic seizures, or other mental illnesses during stroke episodes;

23. Patients who are ready to go or have undergone endovascular treatment;

24. The restricted drug specified in the protocol or any drug that may interfere with the test results must be ingested or desired to continue to be ingested;

25. An expected survival time of no more than 1 year due to other diseases;

26. Patients who are participating in other trials or have participated in other trials within 30 days before randomization;

27. Pregnancy or lactation, or women who have a positive pregnancy test result;

28. The subject who is unsuitable for this study in the opinion of the investigators.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Injection of recombinant human tissue plasminogen kinase derivatives
18mg/10ml/stick, provided by Angde Biotech
• Recombinant human tissue plasminogen activator
20mg/stick, 50mg/stick, provided by Shanghai Boehringer Ingelheim Pharmaceutical Co. Ltd.

Locations

Country	Name	City	State
China	Anyang People's Hospital	Anyang	Henan
China	Inner Mongolia Baogang Hospital	Baotou	Inner Mongolia
China	The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology	Baotou	Inner Mongolia
China	Beijing Tiantan Hospital	Beijing	Beijing
China	Xuanwu Hospital of Capital Medical University	Beijing	Beijing
China	The First Affiliated Hospital of Bengbu Medical College	Bengbu	Anhui
China	Cangzhou Central Hospital	Cangzhou	Hebei
China	Hebei Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine	Cangzhou	Hebei
China	First Hospital of Jilin University	Changchun	Jilin
China	Chongqing Emergency Medical Center	Chongqing	Chongqing
China	Daqing Oilfield General Hospital	Daqing	Heilongjiang
China	Daqing People's Hospital	Daqing	Heilongjiang
China	General Hospital of Tongmei Group	Datong	Shanxi
China	Dezhou People's Hospital	Dezhou	Shandong
China	Fukuang General Hospital of Liaoning Health Industry Group	Fushun	Liaoning
China	Ganzhou People's Hospital	Ganzhou	Jiangxi
China	Gaozhou People's Hospital	Gaozhou	Guangdong
China	Handan Central Hospital	Handan	Hebei
China	The Fourth Affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang
China	Hengshui People's Hospital	Hengshui	Hebei
China	The First Affiliated Hospital of Nanhua University	Hengyang	Hunan
China	Affiliated Hospital of Inner Mongolia Medical University	Hohhot	Inner Mongolia
China	Inner Mongolia Autonomous Region People's Hospital	Hohhot	Inner Mongolia
China	Huai'an Second People's Hospital	Huai'an	Jiangsu
China	Jiangmen Central Hospital	Jiangmen	Guangdong
China	Jiaozuo People's Hospital	Jiaozuo	Henan
China	Jiaxing First Hospital	Jiaxing	Zhejiang
China	Jilin People's Hospital	Jilin	Jilin
China	Jinan Central Hospital	Jinan	Shandong
China	Shandong Qianfo Mountain Hospital	Jinan	Shandong
China	Affiliated Hospital of Jining Medical College	Jining	Shandong
China	First Affiliated Hospital of Jinzhou Medical University	Jinzhou	Liaoning
China	Huaihe Hospital of Henan University	Kaifeng	Henan
China	First People's Hospital of Kashgar Region	Kashgar	Xinjiang
China	Liaocheng People's Hospital	Liaocheng	Shandong
China	Linyi People's Hospital	Linyi	Shandong
China	The First Affiliated Hospital of Henan University of Science and Technology	Luoyan	Henan
China	Luoyang Central Hospital	Luoyang	Henan
China	The First Affiliated Hospital of Henan University of Science and Technology	Luoyang	Henan
China	Meihekou Central Hospital	Meihekou	Jilin
China	Meizhou People's Hospital	Meizhou	Guangdong
China	The Second Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Nanyang Nanshi Hospital	Nanyang	Henan
China	Nanyang Second People's Hospital	Nanyang	Henan
China	Pingxiang People's Hospital	Pingxiang	Jiangxi
China	Qingdao Central Hospital	Qingdao	Shandong
China	The Third Affiliated Hospital of Qiqihar Medical College	Qiqihar	Heilongjiang
China	Shanghai Pudong Hospital	Shanghai	Shanghai
China	Yue Bei People's Hospital	Shaoguan	Guangdong
China	Central Hospital Affiliated to Shenyang Medical College	Shenyang	Liaoning
China	PLA Northern Theater Command General Hospital	Shenyang	Liaoning
China	Shenyang First People's Hospital	Shenyang	Liaoning
China	The First Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	The Second Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Jilin Guowen Hospital	Siping	Jilin
China	Tai'an Central Hospital	Tai'an	Shandong
China	Taizhou First People's Hospital	Taizhou	Zhejiang
China	Tangshan Workers'Hospital	Tangshan	Hebei
China	Tianjin Medical University General Hospital	Tianjin	Tianjin
China	Tianjin People's Hospital	Tianjin	Tianjin
China	Tonghua Central Hospital	Tonghua	Jilin
China	People's Hospital of Xinjiang Uygur Autonomous Region	Urumqi	Xinjiang
China	Weifang Hospital of Traditional Chinese Medicine	Weifang	Shandong
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	Wuhan Fourth Hospital (Wuhan Puai Hospital, Wuhan Orthopaedic Hospital)	Wuhan	Hubei
China	Xi'an Daxing Hospital	Xi'an	Shanxi
China	Xi'an High-tech Hospital 204 Hospital	Xi'an	Shanxi
China	Yan'an University Xianyang Hospital	Xianyang	Shanxi
China	Xinxiang Central Hospital	Xinxiang	Henan
China	Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu
China	Xuzhou Central Hospital	Xuzhou	Jiangsu
China	Yantai Yuhuangding Hospital	Yantai	Shandong
China	Yichun People's Hospital	Yichun	Jiangxi
China	Yiyang Central Hospital	Yiyang	Hunan
China	Zhengzhou People's Hospital	Zhengzhou	Henan
China	Zhuhai People's Hospital	Zhuhai	Guangdong
China	Zhumadian Central Hospital	Zhumadian	Henan
China	Zigong First People's Hospital	Zigong	Sichuan

Sponsors (2)

Lead Sponsor	Collaborator
Angde Biotech Pharmaceutical Co., Ltd.	Beijing Tiantan Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Proportion of subjects died of all cause	All-cause mortality within 7 days and 90 days after treatment.	within 7 days and 90 days after treatment
Other	Percentage of subjects with symptomatic intracranial hemorrhage (sICH)	sICH definition: 1. SITS criteria: local or remote parenchymal hematoma type 2 on the imaging scan obtained within 36 hours after treatment, plus neurologic deterioration, as indicated by a score on the NIHSS that was higher by 4 points or more than the baseline value or the lowest value between baseline and 24 hours, or hemorrhage leading to death. 2. The ECASS III criteria:any hemorrhage with neurologic deterioration, as indicated by an NIHSS score that was higher by 4 points or more than the value at baseline or the lowest value in the first 7 days , or any hemorrhage leading to death. In addition, the hemorrhage must have been identified as the predominant cause of the neurologic deterioration (This study will be evaluated and recorded according to the above two standards).	SITS criteria: within 36 hours after treatment; ECASS III criteria: within 36 hours and 7 days after treatment
Other	Proportion of subjects with major hemorrhage and clinically relevant non-major hemorrhage(ISTH criteria)	ISTH:International Society of Thrombosis and Hemostasis.	within 90 days after treatment
Other	The Proportion of subjects with AE?SAE	The Proportion of subjects with AE?SAE within 90 days after treatment.	within 90 days after treatment
Primary	Functional handicap	Proportion of patients achieving a Modified Rankin Scale score of 0 to 1 on the 90th day after treatment.; The Modified Rankin Score (mRS) is a 6 point disability scale with possible scores ranging from 0-5. A separate category of 6 is usually added for patients who expire. The higher the score, the more severe the stroke.	on the 90th day after treatment
Secondary	Proportion of Neurological Improvement	The proportion of subjects with NIHSS score =1 or the decrease of 4 points or more from the baseline at 24 hours and the 7th day after treatment.; The National Institutes of Health Stroke Scale (NIHSS) is a 11-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on level of consciousness, eye movements, integrity of visual fields, facial movements,arm and leg muscle strength, sensation, coordination, language,speech and neglect. Each impairment is scored on an ordinal scale ranging from 0 to 2, 0 to 3, or 0 to 4. Item scores are summed to a total score ranging from 0 to 42 (the higher the score, the more severe the stroke).	at 24hours and the 7th day after treatment
Secondary	Proportion of Long-term Improvement	Proportion of patients achieving a mRS of 0 to 2 on the 90th day after treatment.	on the 90th day after treatment
Secondary	Ordinary distribution of mRS scores	Ordinary distribution of mRS scores on the 90th day after treatment.	on the 90th day after treatment
Secondary	Barthel Index score	Proportion of patients achieving a Barthel Index score =95 on the 90th day after treatment.; The Barthel Index of Activities of Daily Living (ADLs) measures functional disability by quantifying patient performance in 10 activities of daily life. These activities can be grouped according to self-care (feeding, grooming, bathing, dressing, bowel and bladder care, and toilet use) and mobility (ambulation, transfers, and stair climbing). 5-point increments are used in scoring, with a maximal score of 100 indicating that a patient is fully independent in physical functioning, and a lowest score of 0 representing a totally dependent bed-ridden state.	on the 90th day after treatment