Adjunctive Use of Intra-Arterial TNK and Albumin Following Thrombectomy

Feasibility and Efficacy of Intra- Arterial TNK and Albumin as an Adjunct to Thrombectomy for Acute Stroke

The purpose of this study is to investigate the feasibility and efficacy of intra-arterial TNK and albumin for patients with acute ischemic stroke after successful thrombectomy and whether there is a synergistic effect between TNK and albumin.

Study Overview

• Status: Recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: Intra-Arterial TNK and Albumin; Drug: Intra-Arterial TNK; Drug: Intra-Arterial Albumin; Other: sham

Detailed Description

Endovascular therapy is the first-line treatment for acute ischemic stroke with large vessel occlusion. However, many studies have shown that, even with successful recanalization, about half of patients do not achieve functional independence. This phenomenon is called futile recanalization, which is partly attributed to brain no-reflow (microcirculation reperfusion failure despite recanalization of the occluded large artery). The mechanisms of brain no-reflow phenomenon include inflammation, micro thrombosis, aggregation platelets and red blood cells, and pericyte contraction.

Albumin, the most copious plasma protein synthesized primarily in the liver, possesses various biochemical properties, including anti-inflammatory, inhibiting platelet aggregation and micro thrombosis formation, and increasing microvascular perfusion. All of these properties are directed toward the mechanisms of no-reflow production, so albumin may inhibit no-reflow to improve the prognosis of stroke patients. TNK is a new generation thrombolytic agent that inhibits thrombosis, improves microcirculatory perfusion, and may inhibit no-reflow. These functions of TNK are similar to those of albumin, and the two also can reduce infraction volume and cerebral edema, and improve of behavioral function. In this study, we plan to determine the feasibility and efficacy of intra-arterial TNK and albumin for stroke patients undergoing successful mechanical thrombectomy and whether there is a synergistic effect between TNK and albumin.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300222
      • Recruiting
      • Tianjin Huanhu Hospital
      • Principal Investigator: Ming Wei, PhD
      • Contact: Ming Wei, PhD; Phone Number: 13502182903; Email: drweiming@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. AIS patients with large vessel occlusion;
2. Age between 18 and 80 years;
3. Baseline NIHSS score ≥ 6; 4 .Successful recanalization after thrombectomy (mTICI grades ≥ 2b);

5. ASPECTS score ≥ 6 on CT; 6. First episode or previous episode without significant sequelae (mRS ≤ 2); 7. Time from onset to femoral artery puncture ≤ 24 hours; 8. Written informed consent provided by the patients or their legal relatives.

Exclusion criteria:

1. Upon admission, the patient's medical history and physical examination revealed manifestations indicative of congestive heart failure (CHF), such as jugular venous distention, the presence of a third heart sound, resting tachycardia at a rate of 100 beats per minute attributable to heart failure, hepatomegaly, and/or lower extremity edema attributable to heart failure or of unknown etiology;
2. History of acute myocardial infarction within the preceding 3 months;
3. The patient's medical history, electrocardiogram findings upon admission, or physical examination indicated the presence of second- or third-degree heart block or any arrhythmia associated with hemodynamic instability, as determined by the investigator's assessment;
4. Acute or chronic renal failure with serum creatinine levels exceeding 2.0 mg/dL;
5. Severe anemia characterized by a hematocrit below 32%;
6. Computed tomography findings upon admission indicating the presence of any form of hemorrhage;
7. Pregnancy status;
8. Previous history of allergic reactions to albumin administration or TNK administration;
9. Elevated blood pressure exceeding 185/110 mmHg when investigating the use of albumin administration or TNK administration;
10. Presence of other potentially life-threatening medical conditions;
11. Individuals with current chronic lung diseases, such as chronic obstructive pulmonary disease, bronchiectasis, or any other lung disorder that significantly impairs daily activities;
12. Individuals with known allergies to albumin or TNK;
13. Patients with reocclusion within 24 hours;
14. Clinical suspicion of aortic coarctation、 bacterial embolism and infective endocarditis;
15. Patients with a history of coagulation disorders and systemic bleeding tendencies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: sham	Other: sham; The study population was divided into four groups, one of which had no intra-arterial TNK and albumin.
Active Comparator: Intra-Arterial TNK and Albumin	Drug: Intra-Arterial TNK and Albumin; The study population was divided into four groups, one of which had intra-arterial TNK and albumin.
Active Comparator: Intra-Arterial TNK	Drug: Intra-Arterial TNK; The study population was divided into four groups, one of which had intra-arterial TNK .
Active Comparator: Intra-Arterial Albumin	Drug: Intra-Arterial Albumin; The study population was divided into four groups, one of which had intra-arterial albumin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with major response	Major response is any of the following: Any forms of intracranial hemorrhage;; Pulmonary edema;; Heart failure;; Skin itching, dyspnea and other allergic reactions;; Death of any causes.	7 days after initiation of TNK or albumin intra-arterially

Collaborators and Investigators

• Sponsor: Tianjin Huanhu Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2023
• Primary Completion (Estimated): September 7, 2024
• Study Completion (Estimated): September 7, 2024

Study Registration Dates

• First Submitted: October 27, 2023
• First Submitted That Met QC Criteria: October 27, 2023
• First Posted (Actual): November 2, 2023

Study Record Updates

• Last Update Posted (Actual): November 2, 2023
• Last Update Submitted That Met QC Criteria: October 27, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: TNK; Acute ischemic stroke; Large Vessel Occlusion; Albumin; No-reflow; Endovascular Therapy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: TJHH-2023-wm16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No