Clinical trial NCT06538844: Albumin for Patients With Acute Large Vessel Occlusive Stroke Undergoing Endovascular Reperfusion Therapy
Official title: Albumin for Patients With Acute Large Vessel Occlusive Stroke Undergoing Endovascular Reperfusion Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Ischemic Stroke
Lead sponsor: Capital Medical University
Sponsor class: OTHER
Collaborators: name: Xuanwu Hospital, Beijing
First posted: 2024-08-06
Enrollment: 134
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 objective of this study is to evaluate the effectiveness and safety of endovascular therapy combined with 25% human albumin in the treatment of acute large vessel occlusive stroke.

Detailed description: Stroke is the second leading cause of death worldwide, 85% of which are acute ischemic strokes (AIS). Neuronal death is the primary pathological manifestation of acute ischemic stroke (AIS). Preclinical studies have revealed that neuroprotective agents can reduce neuronal damage and improve neurological outcomes in experimental animals. However, over the past 40 years, clinical translation of neuroprotective drugs has consistently failed. In 2015, with the publication of five randomized controlled trials (RCTs) on thrombectomy for anterior circulation, there was sufficient evidence-based support for thrombectomy in large vessel occlusion of the anterior circulation, ushering us into a new era of AIS treatment - the era of efficient reperfusion therapy. In this context, neuroprotective therapy should be re-examined as an adjunctive approach to reperfusion therapy.

Albumin, the predominant plasma protein synthesized primarily in the liver, possesses various biochemical properties that are expected to confer a neuroprotective effect following acute ischemic stroke.

This study is a multi-center, randomized, double-blind, placebo-controlled clinical study, focusing on patients with acute large vessel occlusive stroke. It aims to investigate the effectiveness and safety of albumin as an adjunctive treatment to endovascular therapy compared with placebo in reducing infarct volume, improving long-term functional outcomes, and daily living activities of patients with acute ischemic stroke in the era of reperfusion therapy.

Eligibility criteria: Inclusion Criteria:

1. Age between 18 and 80 years;
2. Anterior circulation acute ischemic stroke, with acute occlusion of the responsible vessel located in the intracranial segment of the internal carotid artery, or the M1 or M2 segment of the middle cerebral artery;
3. National Institute of Health Stroke Scale (NIHSS) score ≥6;
4. Modified Rankin Scale (mRS) score ≤1 before onset of the disease;
5. Alberta Stroke Program Early CT Score (ASPECTS) ≥3 points;
6. Ischemic-core volume ≤100ml;
7. Patient treatable within 24 hours of symptom onset. Symptoms onset is defined as point in time the patient was last seen well (at baseline) if patients are unable to provide a reliable history or the point in time when symptoms have started if patients can provide a reliable history. Treatment start is defined as groin puncture.;
8. Written informed consent provided by the patients or their legal relatives.

Exclusion Criteria:

1. Evidence of intracranial hemorrhage (intracerebral hematoma (ICH), subarachnoid hemorrhage (SAH), epidural hemorrhage, acute or chronic subdural hematoma (SDH)) on the baseline CT or MRI scan；
2. History of congenital or acquired bleeding disorders, coagulation factor deficiency diseases, thrombocytopenic diseases, etc;
3. Anticipated difficulty in completing endovascular treatment due to vascular tortuosity;
4. Known severe allergy (more severe than skin rash) to contrast agents uncontrolled by medications;
5. Pregnancy, breastfeeding；
6. An episode or exacerbation of congestive heart failure from any cause in the past 6 months;
7. History of heart valve disease complicated by congestive heart failure within the past 6 months；
8. Cardiac surgery with thoracotomy (eg coronary artery bypass grafting or valve replacement surgery) within the past 6 months；
9. Acute myocardial infarction in the past 6 months;
10. Signs or symptoms of acute myocardial infarction upon admission, including electrocardiographic findings；
11. Elevated serum troponin concentration upon admission (\>0.1 μg/L) ；
12. Acute arrhythmia (including any tachycardia or bradycardia) with hemodynamic instability (systolic blood pressure \<100 mm Hg) upon admission；
13. Acute or chronic lung diseases requiring long-term or intermittent oxygen therapy；
14. Findings on physical examination of any of the following abnormalities: (1) Jugular venous distension (jugular venous pulsation \>4 cm above the sternal angle); (2) Resting tachycardia due to congestive heart failure (heart rate \> 100 per/min); (3) Third heart sound; (4) Abnormal hepatic jugular venous reflux; (5) Pitting edema of the lower extremities attributable to congestive heart failure or without apparent cause; (6) Rales in both lungs; (7) Or evidence of pulmonary edema, pleural effusion, or pulmonary vascular redistribution on chest X-ray；
15. Known recent or current serum creatinine exceeding 1.5 times the upper limit of normal, or estimated glomerular filtration rate (eGFR) \< 60 mL/min;
16. Refractory hypertension that is difficult to control by medication (defined as systolic blood pressure \> 220 mmHg, or diastolic blood pressure \> 110 mmHg);
17. Severe chronic anemia (hemoglobin \< 75 g/L);
18. History of albumin allergy or known allergy to albumin;
19. Patients with severe mental disorders or dementia who are unable to cooperate in completing informed consent and follow-up content;
20. The expected survival time is less than 90 days (such as comorbidity with malignant tumor or severe systemic diseases etc.);
21. Patients who have participated in other interventional clinical studies within 30 days prior to randomization or are currently participating in other interventional clinical studies.

Primary outcomes:
measure: Changes in infarction volume from Day 5 to baseline.
timeFrame: From 5 days after surgery to baseline
Secondary outcomes:
measure: Early neurological improvement within 24 hours
timeFrame: within 24 hours
measure: NIHSS score at 24 hours
timeFrame: at 24 hours
measure: Proportion of successful reperfusion (mTICI 2b/3)
timeFrame: immediate postoperative
measure: NIHSS score at 5 days
timeFrame: at 5 days
measure: Proportion of patients with functional independence (mRS 0-1) at 90 days
timeFrame: at 90 days
measure: Proportion of patients with functional independence (mRS 0-2) at 90 days
timeFrame: at 90 days
measure: Proportion of patients with Barthel Index of 95-100 at 90 days
timeFrame: at 90 days
measure: European quality of Life-5 Dimensions (EQ-5D) at 90 days
timeFrame: at 90 days
measure: Incidence of Symptomatic intracerebral hemorrhage (ICH) Within 24 Hours
timeFrame: within 24 hours
measure: Incidence of Intracerebral hemorrhage within 24 Hours
timeFrame: within 24 hours
measure: Neurological deterioration within 24 hours
timeFrame: within 24 hours
measure: Incidence of New-onset atrial fibrillation within 5 days
timeFrame: within 5 days
measure: Incidence of Pulmonary edema or congestive heart failure within 5 days
timeFrame: within 5 days
measure: Incidence of Intracerebral hemorrhage within 5 days
timeFrame: within 5 days
measure: Incidence of Symptomatic intracerebral hemorrhage (ICH) Within 5 days
timeFrame: within 5 days
measure: Incidence of Decompressive craniectomy within 7 days
timeFrame: within 7 days
measure: Death within 90 days
timeFrame: within 90 days
measure: Number of participants who experience adverse events (AEs)
timeFrame: within 90 days
measure: Number of participants who experience serious adverse events (SAEs)
timeFrame: within 90 days
Other outcomes:
Locations:
city: Ma'anshan
country: China
facility: Maanshan People's Hospital
state: Anhui
city: Suzhou
country: China
facility: Suzhou Municipal Hospital of Anhui Province
state: Anhui
city: Luoyang
country: China
facility: Luoyang Central Hospital Affiliated to Zhengzhou University
state: Henan
city: Nanyang
country: China
facility: Nanyang Central Hospital
state: Henan
city: Zhengzhou
country: China
facility: First People's Hospital of Zhengzhou City
state: Henan
city: Zhoukou
country: China
facility: Xihua County People's Hospital
state: Henan
city: Yangzhou
country: China
facility: Northern Jiangsu People's Hospita!
state: Jiangsu
city: Liaocheng
country: China
facility: Liaocheng Third People's Hospital
state: Shandong
Study officials:
References: