Butyphthalide in Combination With Recombinant Tissue Plasminogen Activator for Acute Ischemic Stroke

Butyphthalide in Combination With Recombinant Tissue Plasminogen Activator for Acute Ischemic Stroke (BRAIS)：a Pilot, Prospective, Random, and Double Blinded Multi-center Study

Acute ischemic stroke (AIS) is the most common type of stroke, which has high rate of morbidity, mortality and disability. A large number of studies have confirmed that the thrombolytic therapy can effectively open blood vessels and improve the functional prognosis of acute ischemic stroke. Therefore, all guidelines recommend giving thrombolysis treatment to acute ischemic stroke patients within 4.5 hours of onset. However, about 1/3 patients receiving thrombolysis will have good prognosis, while a large number of patients will still be disabled and even dead. How to improve the neurofunctional prognosis of thrombolytic patients has been a hot topic in the world.

Butyl phthalide is type I chemical drugs. Some multicenter randomized, double-blind, placebo-controlled clinical trials have showed that acute ischemic stroke patients taking butyl phthalide has better lateral branch circulation and living ability score than patients taking placebo. Besides, butyl phthalide treatment is safe. The animal experiment indicated that buphthalein could significantly improve secondary side branch circulation, recover the microarterial diameter of the soft meninges in the ischemic region and increase the blood flow rate.

Based on the discussion, we assume that: giving butyl phthalide to patients with acute ischemic stroke in advance, might promote and improve the formation of collateral circulation to freeze ischemia penumbra. Based on this hypothesis, we would like to explore the efficacy and safety of butyl phthalide combined with rtPA thrombolysis in the treatment of acute ischemic stroke.

Study Overview

• Status: Completed
• Conditions: Stroke, Ischemic
• Intervention / Treatment: Drug: Butyphthalide combined with rtPA; Drug: rtPA

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • ShenYang, China
    • General Hospital of Shenyang Military Region

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age >18 years;
2. Diagnosis of anterior circulation infarct;
3. First stroke onset or past stroke without obvious neurological deficit (mRS≤1);
4. Time from onset to treatment ≤4.5 hours;
5. SBP/DBP ≤ 180/110mmHg;
6. No hemorrhagic imaging changes showed in CT;
7. Signed informed consent by patient self or legally authorized representatives.

Exclusion Criteria:

1. History of stroke within 3 months;
2. History of intracranial hemorrhage;
3. Suspected subarachnoid hemorrhage;
4. Intracranial tumour, vascular malformation or arterial aneurysm;
5. Major surgery within 1 month;
6. Systolic pressure ≥180 mmHg or diastolic pressure ≥110 mmHg;
7. Platelet count < 100×109／L;
8. Heparin therapy or oral anticoagulation therapy within 48 hours;
9. Severe disease with a life expectancy of less than 3 months;
10. Blood glucose < 50 mg/dL (2.7mmol/L);
11. Patients who have received any other investigational drug or device within 3 months;
12. Researchers consider patients inappropriate to participate in the registry. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: rtPA combined with Butyphthalide; Intravenous treatment with 25mg butyphthalide, followed by intravenous throbolysis with 0.9mg/kg rtPA. Next day, intravenous treatment with 25mg butyphthalide 2 times/day for 14 days, followed by oral butyphthalide capsule (0.2g 3 times/day) to 90 days after thrombolysis. Other treatments were done according to guidelines.	Drug: Butyphthalide combined with rtPA; Intravenous treatment with 25mg butyphthalide, followed by intravenous throbolysis with 0.9mg/kg rtPA. Next day, intravenous treatment with 25mg butyphthalide 2 times/day for 14 days, followed by oral butyphthalide capsule (0.2g 3 times/day) to 90 days after thrombolysis. Other treatments were done according to guidelines.
ACTIVE_COMPARATOR: rtPA compared with placebo; Intravenous treatment with placebo injection, followed by intravenous throbolysis with 0.9mg/kg rtPA. Next day, intravenous treatment with placebo injection 2 times/day for 14 days, followed by oral placebo capsule (3 times/day) to 90 days after thrombolysis. Other treatments were done according to guidelines.	Drug: rtPA; Intravenous thrombolysi with 0.9mg/kg rtPA, followed by other treatments according to guidelines

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of mRS score (0-2) (90 days)	Percentage of mRS score (0-2) at 90 days	90 days

Collaborators and Investigators

• Sponsor: Hui-Sheng Chen

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 25, 2018
• Primary Completion (ACTUAL): May 29, 2021
• Study Completion (ACTUAL): May 29, 2021

Study Registration Dates

• First Submitted: January 3, 2018
• First Submitted That Met QC Criteria: January 3, 2018
• First Posted (ACTUAL): January 9, 2018

Study Record Updates

• Last Update Posted (ACTUAL): June 2, 2021
• Last Update Submitted That Met QC Criteria: June 1, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: thrombolysis; Butyphthalide
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Ischemia; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator
• Other Study ID Numbers: k201731

Drug and device information, study documents

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