Efficacy and Safety of Intra-Arterial Albumin as Adjunct to Mechanical Thrombectomy in Acute Ischemic Stroke

Official title

Efficacy and Safety of Intra-Arterial Albumin as Adjunct to Mechanical Thrombectomy in Acute Ischemic Stroke: A Multicenter, Prospective, Open-Label, Endpoint-Blinded, Randomized Controlled Clinical Trial (AMASS2)

Overview

Stroke remains a predominant global public health challenge, ranking as the third leading cause of death and the fourth leading contributor to disability-adjusted life years (DALYs). According to the Global Burden of Disease Study 2021, there are approximately 93.8 million prevalent stroke cases and 11.9 million new cases worldwide. China bears one of the heaviest burdens, with over 2 million new cases annually. Acute ischemic stroke (AIS), caused by acute cerebrovascular occlusion, accounts for 80% of all strokes. Approximately 30% of AIS cases result from large vessel occlusion (LVO), which typically carries a poor prognosis due to the extensive area of infarction . Research indicates that early recanalization significantly improves clinical outcomes. Currently, intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are the standard treatments for achieving recanalization . For LVO-related AIS, MT has become the preferred clinical approach due to its extended therapeutic window and superior recanalization rates . However, despite successful recanalization in over 70% of patients, nearly 50% fail to achieve functional independence at 90 days, and mortality remains above 15% . Therefore, enhancing long-term functional outcomes in post-MT patients is a critical unmet clinical need. Human albumin is the most abundant protein in plasma. Beyond maintaining colloid osmotic pressure, it also possesses multiple biological effects, including anti-inflammatory, anti-platelet aggregation, antioxidant, and endothelial protective properties. We conducted a Phase I clinical trial (AMASS-1) for patients post-mechanical thrombectomy, administering human albumin via the internal carotid artery. The results showed that intra-arterial infusion of 20% human albumin at a dose of 0.60 g/kg was safe, with no significant differences in serious adverse reactions such as mortality \[Albumin group (6.7%) vs Control group (6.7%), P \> 0.05\] and symptomatic intracranial hemorrhage \[Albumin group (6.7%) vs Control group (13.3%), P \> 0.05\] compared to the control group. In summary, albumin adjunctive therapy demonstrates good safety and potential neuroprotective effects in patients after mechanical thrombectomy. To further systematically evaluate its efficacy and safety, we plan to conduct a Phase II clinical trial of mechanical thrombectomy combined with intra-arterial albumin infusion for acute ischemic stroke. This is a multicenter, prospective, open-label, endpoint-blinded, randomized controlled trial designed to evaluate the efficacy and safety of intra-arterial infusion of 20% human serum albumin combined with mechanical thrombectomy versus mechanical thrombectomy alone in patients with acute ischemic stroke due to anterior circulation large vessel occlusion who have achieved recanalization after mechanical thrombectomy. A total of 306 patients are planned to be enrolled and randomly assigned in a 1:1 ratio using a dynamic minimization method to two groups: the Albumin Group (0.6 g/kg 20% human serum albumin plus Mechanical Thrombectomy) and the Control Group (Mechanical Thrombectomy alone). The primary efficacy objective of this study is to evaluate whether immediate intra-arterial infusion of 20% human albumin (0.6 g/kg) via the internal carotid artery following successful recanalization (eTICI ≥2b) improves clinical outcomes in patients with acute anterior circulation large vessel occlusion stroke, compared with mechanical thrombectomy alone. The study also aims to evaluate the safety and feasibility of immediate intra-arterial infusion of 20% human albumin (0.6 g/kg) via the internal carotid artery in patients with acute anterior circulation large vessel occlusion stroke who have achieved successful recanalization (eTICI ≥2b) following standard mechanical thrombectomy.

Interventions

• Drug 20% human serum albumin
  20% human albumin solution at a dose of 0.60g/kg will be administered as a constant-rate infusion into the proximal internal carotid artery over 20 minutes.

Primary outcome measures

• Distribution of mRS scores at 90 (±14) days post-randomization [Time frame: at 90 (±14) days post-randomization]

Secondary outcome measures (12)

• Proportion of subjects with a favorable outcome at 90 (±14) days post-randomization (defined as mRS 0-2); [Time frame: at 90 (±14) days post-randomization]
• Proportion of subjects with functional independence at 90 (±14) days post-randomization (defined as mRS 0-1) [Time frame: at 90 (±14) days post-randomization]
• Infarct volume at 24 (±6) hours post-randomization (measured via MRI-DWI) [Time frame: at 24 (±6) hours post-randomization]
• Infarct volume growth from baseline to 24 (±6) hours post-randomization [Time frame: from baseline to 24 (±6) hours post-randomization]
• Recanalization rate at 24 (±6) hours post-randomization [Time frame: at 24 (±6) hours post-randomization]
• NIHSS score at 24 (±6) hours post-randomization [Time frame: at 24 (±6) hours post-randomization]
• NIHSS score at 7 (±1) days or at discharge, whichever occurs first [Time frame: at 7 (±1) days or at discharge, whichever occurs first]
• EQ-5D-5L score at 90 (±14) days post-randomization [Time frame: at 90 (±14) days post-randomization]
• Proportion of subjects with a Barthel Index (BI) ≥95 at 90 (±14) days post-randomization [Time frame: at 90 (±14) days post-randomization]
• Distribution of mRS scores at 180 (±30) days and 1 year (±30 days) post-randomization [Time frame: at 180 (±30) days and 1 year (±30 days) post-randomization]
• Proportion of subjects with a favorable outcome (mRS 0-2) at 180 (±30) days and 1 year (±30 days) post-randomization [Time frame: at 180 (±30) days and 1 year (±30 days) post-randomization]
• EQ-5D-5L score at 180 (±30) days and 1 year (±30 days) post-randomization [Time frame: at 180 (±30) days and 1 year (±30 days) post-randomization]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years
• Acute anterior circulation large vessel occlusion (including ICA/MCA-M1 tandem occlusion or isolated MCA-M1 occlusion) confirmed by CTA, MRA, or DSA, with successful recanalization (eTICI score ≥2b) confirmed by the final intraoperative DSA following mechanical thrombectomy
• Baseline NIHSS scores ≥ 6
• Non-contrast CT ASPECTS ≥6
• Time from stroke onset (or last known well) to arterial puncture within 24 hours
• Pre-stroke functional independence, defined as a modified Rankin Scale (mRS) score <2
• Written informed consent obtained from the patient or a legally authorized representative

Exclusion criteria

• Intracranial hemorrhage confirmed by cranial CT or MRI
• Midline shift with significant mass effect on cranial CT or MRI
• Isolated internal carotid artery (ICA) occlusion
• History of heart failure or severe cardiovascular disease, including but not limited to pulmonary hypertension or pericardial effusion
• Hemodynamically unstable arrhythmia (based on patient self-report or detected prior to infusion)
• Symptoms or electrocardiographic evidence of acute myocardial infarction upon admission
• Acute or chronic renal failure (serum creatinine >2.0 mg/dL
• Severe anemia (hematocrit <32%
• Known hypersensitivity to albumin or blood products
• Pregnancy
• Persistent hypertension (blood pressure ≥180/100mmHg) prior to albumin infusion
• Current participation in other clinical trials
• Life expectancy of less than 3 months
• Concomitant severe pulmonary disease, such as chronic obstructive pulmonary disease, pulmonary fibrosis, pleural effusion, or acute respiratory distress syndrome
• Any other condition that, in the opinion of the investigator, renders the patient unsuitable for participation in the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07365475 · TJHH_WM_20260111

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗