Acute Ischemic Stroke
Conditions
Brief summary
This study is designed to determine the safety and efficacy of SHPL-49 intravenous infusion for 7 consecutive days in the treatment of acute ischemic stroke subjects.
Detailed description
Trial Objectives: The primary objective of this study is to determine the effectiveness of different doses of SHPL-49 intravenous infusion for 7 consecutive days in the treatment of acute ischemic stroke subjects within 8h after onset. The secondary objective is to determine the safety of different doses of SHPL-49 intravenous infusion for 7 consecutive days in the treatment of acute ischemic stroke subjects within 8h after onset. Trial Design: This study is a Phase II, multicenter, randomized, double Blind, placebo-Controlled design. Participants receive twice daily dosing for 7 consecutive days, or once on Days 1 and Day 8 and twice daily on Days 2 to Day 7, with each subject scheduled to receive 14 doses throughout the clinical trial. 270 Participants will be randomized 1:1:1 to SHPL-49 injection treated group (3 ampoules of SHPL-49 injections, Bis in die（BID）), SHPL-49 injection treated group (6 ampoules of SHPL-49 injections , BID) and placebo group (BID).
Interventions
DRUG3 ampoules of SHPL-49 Injection
3 ampoules of SHPL-49 Injection in 100 mL 0.9% sodium chloride will be administered as a 30-minute intravenous infusion and applied twice daily for 7 days.
DRUG6 ampoules of SHPL-49 Injection
6 ampoules of SHPL-49 Injection in 100 mL 0.9% sodium chloride will be administered as a 30-minute intravenous infusion and applied twice daily for 7 days.
DRUG0.9% Sodium Chloride Injection
100 mL 0.9% sodium chloride will be administered as a 30-minute intravenous infusion and applied twice daily for 7 days.
Sponsors
Beijing Tiantan Hospital
Shanghai Hutchison Pharmaceuticals Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-80 years old (including upper and lower limits); 2. Clinically diagnosed as acute ischemic stroke according to the latest guidelines; 3. Patients with acute ischemic stroke who plan to receive or have received standard intravenous thrombolysis in hospital (this research center) within 8h after the onset of the disease; 4. Participants who have NIHSS ≥5 and ≤ 22 before thrombolysis; 5. Pre-stroke mRS Score ≤1; 6. Participants or legally authorized representatives who are able and willing to sign informed consent.
Exclusion criteria
1. Complicated with intracranial hemorrhagic diseases, including hemorrhagic stroke, epidural hematoma, intracranial hematoma, ventricular hemorrhage, subarachnoid hemorrhage, etc.; 2. Severe disturbance of consciousness: patients with NIHSS 1a consciousness level item score ≥2; 3. Cerebral Computed tomography (CT) or Magnetic resonance imaging (MRI) indicated a large anterior circulation cerebral infarction (ASPECT score \< 6 or infarct area greater than 1/3 of the middle cerebral artery blood supply area); 4. Stroke with rapid improvement of symptoms before intravenous thrombolysis, or acute ischemic symptoms suspected to be caused by other causes; 5. Patients who are ready to receive or have receive intravascular therapy; 6. After the onset of the disease, drugs with neuroprotective effects have been applied in the instructions. Such as commercially available Edaravone, Edaravone and Dexborneol Concentrated Solution for Injection, Butylphthalide, Nimodipine, Ganglioside, Citicoline, Piracetam, Oxiracetam, Human Urinary Kallidinogenase, Cinepazide, Mouse Nerve Growth Factor For Injection, Cerebrolysin, Deproteinised Calf Blood Serum Injection, Deproteinised Calf Blood Extractives Injection, etc.; 7. Severe hypertension: systolic blood pressure ≥185mmHg or diastolic blood pressure ≥110mmHg after taking antihypertensive drugs before thrombolysis; 8. Severe renal insufficiency: serum creatinine \>2 times the upper limit of normal or creatinine clearance (CLcr)\< 30mL/min (Cockcroft-Gault formula), or other known severe renal insufficiency; (Note: Cockcroft-Gault formula: ① Male: CLcr (mL/min) = \[140 - age (yrs)\]× body weight (kg) / \[0.814 × serum creatinine (μmol/L)\]; (2) female: CLcr (mL/min) = {\[140 - age (years old)\] by weight (kg) / \[0.814 x serum creatinine (μmol/L)\]} x 0.85) 9. Severe liver function impairment: Alanine aminotransferase (ALT) or Aspartate aminotransferase(AST)\>3 times the upper limit of normal, or other known liver diseases such as acute and chronic hepatitis, cirrhosis, etc.; 10. Patients with a heart function rating above Class II (according to the New York Heart Association (NYHA) heart function rating) or a history of congestive heart failure; 11. Patients with concurrent malignant tumors or undergoing anti-tumor therapy; 12. Allergic to experimental drugs or similar ingredients or materials used in imaging examinations; 13. Patients during pregnancy, breastfeeding or planning pregnancy; 14. Patients who have a history of epilepsy or have had seizure-like symptoms at the onset of stroke, or suffer from serious mental disorders, intellectual disabilities or dementia; 15. Suspected or confirmed alcohol dependence, or drinking more than 3 units (male) or 2 units (female) of alcohol within 24 hours prior to onset (1 unit =360 mL beer or 45 mL liquor with 40% alcohol or 150 mL wine); 16. Patients have participated in or are participating in another clinical study within the 3 months before singing informed consent; 17. Patients who are judged unsuitable for participation by the investigators in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Modified Rankin Scale (mRS), with scores of 0-1 at Day 90 | 90±7 days | Proportion of participants with mRS scores of 0-1 at Day 90 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | 90±7 days | Adverse events over the 90-day study period |
| Barthel inde (BI) at Day 90 | 90±7 days | Proportion of participants with BI ≥95 at Day 90 |
| Serious adverse events | 90±7 days | Serious adverse events over the 90-day study period |
| Symptomatic intracranial hemorrhage | 22-36h after thrombolysis | Symptomatic intracranial hemorrhage within 36h after thrombolysis (Safe Implementation of Thrombolysis in Stroke-Monitoring Study Criteria) |
| Shift analysis/ Ordinal analysis | 90±7 days | A shift of one or more categories to reduced functional dependence analyzed across the whole distribution of outcomes on the mRS at Day 90 |
| Modified Rankin Scale (mRS), with scores of 0-1 at Day 30 | 30±3 days | Proportion of participants with mRS Scores of 0-1 at Day 30 |
| Modified Rankin Scale (mRS), with scores of 0-2 at Day 30 | 30±3 days | Proportion of participants with mRS Scores of 0-2 at Day 30 |
| Modified Rankin Scale (mRS), with scores of 0-2 at Day 90 | 90±7 days | Proportion of participants with mRS Scores of 0-2 at Day 90 |
| Mortality | 90±7 days | Mortality over the 90-day study period |
| National Institute of Health stroke scale (NIHSS) at Day 14 or at discharge | 14±2 days | The proportion of participants with NIHSS scores of 0 to 1 or with 4 points reduction from baseline on day 14 or at discharge |
| Barthel index (BI) at Day 30 | 30±3 days | Proportion of participants with Barthel index ≥95 at Day 30 |
| Changes in laboratory test indicators | 7 days or 8 days，14±2 days，90±7 days | Changes in laboratory test indicators on day 7 or 8(at the end of the last dose), at Day 14 or at discharge, and at Day 90 |
| Changes in vital signs before and after administration | 7 days or 8 days，14±2 days，90±7 days | Changes in vital signs on day 7 or 8 (at the end of the last dose), at Day14 or at discharge , and at Day 90 |
| 12-lead electrocardiogram | 90±7 days | Abnormal 12-lead electrocardiogram over the 90-day study period |
| Vital signs | 90±7 days | Abnormal vital signs over the 90-day study period |
| Physical examination | 90±7 days | Abnormal results of physical examination over the 90-day study period |
| Laboratory test indicators | 90±7 days | Abnormal laboratory test indicators over the 90-day study period |
| National Institute of Health stroke scale (NIHSS) on day 7or 8 | 7 days or 8 days | The proportion of participants with NIHSS scores of 0-1 or with ≥4 point reduction from baseline on day 7 or 8 (after the completion of the final dose) |
Countries
China
Outcome results
None listed