Clinical trial NCT05295173: A Study of r-PA Treating Patients With Acute Ischemic Stroke（RAISE）
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Ischemic Stroke
Lead sponsor: Angde Biotech Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Beijing Tiantan Hospital
First posted: 2022-03-25
Enrollment: 1412
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 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Functional handicap
timeFrame: on the 90th day after treatment
Secondary outcomes:
measure: Proportion of Neurological Improvement
timeFrame: at 24hours and the 7th day after treatment
measure: Proportion of Long-term Improvement
timeFrame: on the 90th day after treatment
measure: Ordinary distribution of mRS scores
timeFrame: on the 90th day after treatment
measure: Barthel Index score
timeFrame: on the 90th day after treatment
Other outcomes:
measure: Proportion of subjects died of all cause
timeFrame: within 7 days and 90 days after treatment
measure: Percentage of subjects with symptomatic intracranial hemorrhage (sICH)
timeFrame: SITS criteria: within 36 hours after treatment; ECASS III criteria: within 36 hours and 7 days after treatment
measure: Proportion of subjects with major hemorrhage and clinically relevant non-major hemorrhage（ISTH criteria）
timeFrame: within 90 days after treatment
measure: The Proportion of subjects with AE、SAE
timeFrame: within 90 days after treatment
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Beijing
country: China
facility: Xuanwu Hospital of Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Tiantan Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing Emergency Medical Center
state: Chongqing
city: Gaozhou
country: China
facility: Gaozhou People's Hospital
state: Guangdong
city: Jiangmen
country: China
facility: Jiangmen Central Hospital
state: Guangdong
city: Meizhou
country: China
facility: Meizhou People's Hospital
state: Guangdong
city: Shaoguan
country: China
facility: Yue Bei People's Hospital
state: Guangdong
city: Zhuhai
country: China
facility: Zhuhai People's Hospital
state: Guangdong
city: Cangzhou
country: China
facility: Cangzhou Central Hospital
state: Hebei
city: Cangzhou
country: China
facility: Hebei Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine
state: Hebei
city: Handan
country: China
facility: Handan Central Hospital
state: Hebei
city: Hengshui
country: China
facility: Hengshui People's Hospital
state: Hebei
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University
state: Hebei
city: Shijiazhuang
country: China
facility: The First Hospital of Hebei Medical University
state: Hebei
city: Tangshan
country: China
facility: Tangshan Workers'Hospital
state: Hebei
city: Daqing
country: China
facility: Daqing Oilfield General Hospital
state: Heilongjiang
city: Daqing
country: China
facility: Daqing People's Hospital
state: Heilongjiang
city: Harbin
country: China
facility: The Fourth Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Qiqihar
country: China
facility: The Third Affiliated Hospital of Qiqihar Medical College
state: Heilongjiang
city: Anyang
country: China
facility: Anyang People's Hospital
state: Henan
city: Jiaozuo
country: China
facility: Jiaozuo People's Hospital
state: Henan
city: Kaifeng
country: China
facility: Huaihe Hospital of Henan University
state: Henan
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technology
state: Henan
city: Luoyang
country: China
facility: Luoyang Central Hospital
state: Henan
city: Luoyan
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technology
state: Henan
city: Nanyang
country: China
facility: Nanyang Nanshi Hospital
state: Henan
city: Nanyang
country: China
facility: Nanyang Second People's Hospital
state: Henan
city: Xinxiang
country: China
facility: Xinxiang Central Hospital
state: Henan
city: Zhengzhou
country: China
facility: Zhengzhou People's Hospital
state: Henan
city: Zhumadian
country: China
facility: Zhumadian Central Hospital
state: Henan
city: Wuhan
country: China
facility: Wuhan Fourth Hospital (Wuhan Puai Hospital, Wuhan Orthopaedic Hospital)
state: Hubei
city: Hengyang
country: China
facility: The First Affiliated Hospital of Nanhua University
state: Hunan
city: Yiyang
country: China
facility: Yiyang Central Hospital
state: Hunan
city: Baotou
country: China
facility: Inner Mongolia Baogang Hospital
state: Inner Mongolia
city: Baotou
country: China
facility: The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology
state: Inner Mongolia
city: Hohhot
country: China
facility: Inner Mongolia Autonomous Region People's Hospital
state: Inner Mongolia
city: Hohhot
country: China
facility: Affiliated Hospital of Inner Mongolia Medical University
state: Inner Mongolia
city: Huai'an
country: China
facility: Huai'an Second People's Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
state: Jiangsu
city: Ganzhou
country: China
facility: Ganzhou People's Hospital
state: Jiangxi
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Pingxiang
country: China
facility: Pingxiang People's Hospital
state: Jiangxi
city: Yichun
country: China
facility: Yichun People's Hospital
state: Jiangxi
city: Changchun
country: China
facility: First Hospital of Jilin University
state: Jilin
city: Jilin
country: China
facility: Jilin People's Hospital
state: Jilin
city: Meihekou
country: China
facility: Meihekou Central Hospital
state: Jilin
city: Siping
country: China
facility: Jilin Guowen Hospital
state: Jilin
city: Tonghua
country: China
facility: Tonghua Central Hospital
state: Jilin
city: Fushun
country: China
facility: Fukuang General Hospital of Liaoning Health Industry Group
state: Liaoning
city: Jinzhou
country: China
facility: First Affiliated Hospital of Jinzhou Medical University
state: Liaoning
city: Shenyang
country: China
facility: PLA Northern Theater Command General Hospital
state: Liaoning
city: Shenyang
country: China
facility: Shenyang First People's Hospital
state: Liaoning
city: Shenyang
country: China
facility: Central Hospital Affiliated to Shenyang Medical College
state: Liaoning
city: Dezhou
country: China
facility: Dezhou People's Hospital
state: Shandong
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Jinan
country: China
facility: Shandong Qianfo Mountain Hospital
state: Shandong
city: Jining
country: China
facility: Affiliated Hospital of Jining Medical College
state: Shandong
city: Liaocheng
country: China
facility: Liaocheng People's Hospital
state: Shandong
city: Linyi
country: China
facility: Linyi People's Hospital
state: Shandong
city: Qingdao
country: China
facility: Qingdao Central Hospital
state: Shandong
city: Tai'an
country: China
facility: Tai'an Central Hospital
state: Shandong
city: Weifang
country: China
facility: Weifang Hospital of Traditional Chinese Medicine
state: Shandong
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Pudong Hospital
state: Shanghai
city: Datong
country: China
facility: General Hospital of Tongmei Group
state: Shanxi
city: Xi'an
country: China
facility: Xi'an Daxing Hospital
state: Shanxi
city: Xi'an
country: China
facility: Xi'an High-tech Hospital 204 Hospital
state: Shanxi
city: Xianyang
country: China
facility: Yan'an University Xianyang Hospital
state: Shanxi
city: Zigong
country: China
facility: Zigong First People's Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin People's Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Kashgar
country: China
facility: First People's Hospital of Kashgar Region
state: Xinjiang
city: Urumqi
country: China
facility: People's Hospital of Xinjiang Uygur Autonomous Region
state: Xinjiang
city: Jiaxing
country: China
facility: Jiaxing First Hospital
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou First People's Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
affiliation: Beijing Tiantan Hospital
name: Yongjun Wang
role: PRINCIPAL_INVESTIGATOR
References: