Efficacy and Safety of Butylphthalide for Acute Ischemic Stroke Patients Receiving Intravenous Thrombolysis or Endovascular Treatment

NCT03539445 | Completed Phase 3 DMC

• 1 other identifier: 2016YFC1301501
• Study Type: interventional
• Target: 1,216
• Locations: 1 country
• Sites: 1

Brief Summary

Butylphthalide, as a well-known neuroprotective medication, is a family of compounds initially isolated from the seeds of Apium graveolens Linn, of which active ingredient is dl-3-N-butylphthalide (dl-NBP). With the significant effects of reducing the cerebral ischemic damage and eventually improving patients' clinical outcomes, by the potential mechanisms of promoting microcirculation, as well as releasing oxidative stress, mitochondrial dysfunction and poststroke inflammation, dl-NBP has been widely applied in acute ischemic stroke as an anti-ischemic drug in China since 2002. While with the evolution of using iv. recombinant tissue plasminogen activator（rtPA ）and mechanical thrombectomy in acute ischemic stroke（AIS）patients, it is still undefined whether combination therapy with dl-NBP could enhance the curative effect. The primary purpose of this trial is to evaluate the recovery of neurological deficits in AIS patients who receive iv-rtPA and/or mechanical thrombectomy with the a 3-month regimen of Butylphthalide and Sodium Chloride Injection 100ml twice/day in the initial 14 days and Butylphthalide Soft Capsules 0.2g triple/day for the rest 15th to 90th day therapy versus a 3-month regimen of Butylphthalide Placebo Injection 100ml twice/day in the initial 14 days and followed by Butylphthalide Placebo Soft Capsules 0.2g triple/day for the rest 15th to 90th day therapy.

Conditions

Acute Ischemic Stroke

Keywords

AIS; butylphthalide; mechanical thrombectomy; iv-rtPA; recovery of dysfunction

Outcome Measures

Primary Outcomes (1)

• Favorable outcome

  A modified Rankin Scale score of 0 in patients with a baseline NIHSS core of 4 to 7, a modified Rankin Scale score of 0 to 1 in patients with a baseline NIHSS score of 8 to 14, and a modified Rankin Scale score of 0 to 2 in patients with a baseline NIHSS score of 15 to 25.

  90 days

Secondary Outcomes (19)

• Neurological recovery

  90 days

• Cerebral infarction volume

  14 days

• Recanalization rate

  24 hours

• Symptomatic intracranial hemorrhage

  24 hours

• Recurrent stroke

  90 days

Study Arms (2)

Butylphthalide

EXPERIMENTAL

Drug: Butylphthalide Sodium Chloride Injection and Butylphthalide Soft Capsules

Drug: Butylphthalide

Placebos

PLACEBO COMPARATOR

Drug: Butylphthalide Placebo Injection and Butylphthalide Placebo Soft Capsules

Drug: Butylphthalide Placebo

Interventions

Butylphthalide DRUG

This group will receive a 3-month regimen of Butylphthalide and Sodium Chloride Injection 100ml twice/day in the initial 14 days and Butylphthalide Soft Capsules 0.2g triple/day for the rest Day 15 to Day 90.

Also known as: dl-NBP

Butylphthalide

Butylphthalide Placebo DRUG

This group will receive a 3-month regimen of Butylphthalide Placebo Injection 100ml twice/day in the initial 14 days and Butylphthalide Placebo Soft Capsules 0.2g triple/day for the rest Day 15 to Day 90.

Also known as: Blank

Placebos

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female or male aged ≥ 18 years.
• Acute ischemic stroke.
• Within 6 hours from symptom onset.
• Baseline NIHSS range 4 from 25.
• Proceed to iv-rtPA or intravascular therapy including arterial thrombolysis and mechanical thrombectomy or bridging therapy.
• Provision of informed consent.

You may not qualify if:

• Modified Rankin Scale（mRS）\>1 at randomization (pre-morbid historical assessment).
• ASPECT ≤ 6 confirmed by the pre-operation CT scan.
• Diagnosis of intracranial hemorrhagic disease, such as intracranial hemorrhage, subarachnoid hemorrhage and so on.
• Use any drugs related to Butylphthalide during onset between randomization.
• Dysphagia at the onset of stroke.
• History of coagulation dysfunction, systemic bleeding, neutropenia or thrombocytopenia.
• History of chronic hepatopathy, liver and kidney dysfunction, elevating Alanine transaminase (\> 3 times normal upper limit), elevating serum creatinine (\> 2 times normal upper limit).
• History of severe cardio-pulmonary diseases which is not suitable for this study judged by investigator.
• History of bradycardia (heart rate \< 60 beats/m) and Sick sinus syndrome.
• Severe non-cardiovascular comorbidity with life expectancy \< 3 months or failed to follow the study for other reasons.
• History of drug or food allergy, or are known to be allergic to the drug components of this study.
• Contraindications for the digital subtraction angiography procedure, including severe allergy for contrast agent with or without Iodine.
• Pregnancy or lactation, and women of childbearing age not practicing reliable contraception who do not have a documented negative pregnancy test.
• Incapable to follow this study for mental illness, cognitive or emotional disorder.
• Unsuitable for this study in the opinion of the investigators.

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead

Study Sites (1)

Beijing Tiantan Hospital

Beijing, Beijing Municipality, 100050, China

Location

Related Publications (2)

• Wang A, Jia B, Zhang X, Huo X, Chen J, Gui L, Cai Y, Guo Z, Han Y, Peng Z, Jing P, Chen Y, Liu Y, Yang Y, Wang F, Sun Z, Li T, Sun H, Yuan H, Shao H, Gao L, Zhang P, Wang F, Cao X, Shi W, Li C, Yang J, Zhang H, Wang F, Deng J, Liu Y, Deng W, Song C, Chen H, He L, Zhao H, Li X, Yang H, Zhou Z, Wang Y, Miao Z; BAST Investigators. Efficacy and Safety of Butylphthalide in Patients With Acute Ischemic Stroke: A Randomized Clinical Trial. JAMA Neurol. 2023 Aug 1;80(8):851-859. doi: 10.1001/jamaneurol.2023.1871.

  PMID: 37358859 DERIVED

• Zhang X, Wang A, Zhang JY, Jia B, Huo X, Zuo Y, Tian X, Wang Y, Miao Z; BAST study investigators. Efficacy and safety of butylphthalide for patients who had acute ischaemic stroke receiving intravenous thrombolysis or endovascular treatment (BAST trial): study protocol for a randomised placebo-controlled trial. BMJ Open. 2021 May 25;11(5):e045559. doi: 10.1136/bmjopen-2020-045559.

  PMID: 34035100 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Interventions

3-n-butylphthalide

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Department of Neurological Intervention, Tian Tan Hospital

Study Record Dates

• First Submitted: April 9, 2018
• First Posted: May 29, 2018
• Study Start: July 1, 2018
• Primary Completion: May 22, 2022
• Study Completion: July 31, 2022
• Last Updated: August 5, 2022

Record last verified: 2022-08

Locations

CN (1)