Neuroprotective Effect of Butylphthalide for Cardiac Arrest Patients

Neuroprotective Effect of Butylphthalide Injection on Patients With Return of Spontaneous Circulation After Cardiac Arrest：a Multicenter, Randomized Clinical Trial

Cardiac arrest is one of the critical illnesses that is directly life-threatening, and patients who survive cardiac arrest develop severe neurological deficits or even die. The effectiveness of drugs to improve neurological function in resuscitated brain-injured patients has been a focus of research in the field of resuscitation. Butanephthalein has an ameliorating effect on the damage of central nervous function in patients with acute ischemic stroke, and can promote the improvement of patients' neurological deficits. On this basis, the present study was designed as a multicenter, prospective randomized controlled experiment, with internationally accepted methods for assessing near-term and long-term neurological function, to determine the effectiveness of butalbital in improving neurological function after cardiac arrest, with the aim of searching for new methods and ideas to improve neurological function and prognosis after cardiac arrest.

Study Overview

• Status: Recruiting
• Conditions: Cardiac Arrest; Butylphthalide; Neuroprotective Drugs
• Intervention / Treatment: Drug: Butylphthalide and Sodium Chloride Injection; Drug: Saline Solution

• Study Type: Interventional
• Enrollment (Estimated): 350
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ziren Tang, Ph.D; Phone Number: +86 010-85231530; Email: tangziren1970@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100020
      • Recruiting
      • Beijing Chao-Yang Hospital
      • Contact: Hao Cui, M.D; Phone Number: +86 15726621992; Email: cuihao1337@outlook.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 18-80 years old.
2. Glasgow Coma Scale (GCS) scores ≤8 upon admission.
3. Return of Spontaneous Circulation (ROSC) ≥30min.
4. Signed the informed consent form.

Exclusion Criteria:

1. Cardiac arrest due to irreversible causes such as trauma, poisoning, etc.
2. Cardiac arrest due to end-stage conditions such as advanced cancer.
3. Persistent cardiogenic shock that is unreversed (defined as a systolic blood pressure persistently <90mmHg despite treatment with fluid resuscitation, vasopressor agents, and inotropic medications).
4. Presence of pre-existing cerebrovascular disease prior to cardiac arrest or confirmed intracranial hemorrhage by CT scan following admission.
5. Pre-existing CPC scores of 3-5 prior to cardiac arrest.
6. Prior use of NBP or any medication containing NBP before cardiac arrest.
7. Presence of severe hepatic or renal dysfunction before cardiac arrest (defined as ≥3× upper limit of normal alanine transaminase or ≥2× upper limit of normal creatinine).
8. Bradycardia or sick sinus syndrome occurs after ROSC.
9. History of prior drug or food allergies, or known allergies to the medication components used in this study.
10. Existence of treatment limitations (patient or their legal representative refusing advanced life support treatment, including mechanical ventilation, chest compressions, targeted temperature management, etc.).
11. Presence of severe bleeding tendency upon admission.
12. Body temperature <30℃ upon admission.
13. Pregnant or lactating women, or reproductive-age females with elevated serum human Chorionic Gonadotropin (hCG) levels.
14. Other conditions deemed unsuitable for this trial by the principal investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Butylphthalide; Butylphthalide and Sodium Chloride Injection 100ml ivgtt bid 14days	Drug: Butylphthalide and Sodium Chloride Injection; All enrolled patients will undergo standard treatment as per international guidelines, concurrently receiving either NBP or placebo therapy. Patients in the experimental group will receive intravenous infusion of 100ml NBP injection twice daily, while patients in the control group will receive intravenous infusion of 100ml saline solution twice daily. Each patient will receive continuous medication for 14 days.
Placebo Comparator: Saline Solution; Saline Solution 100ml ivgtt bid 14days	Drug: Saline Solution; All enrolled patients will undergo standard treatment as per international guidelines, concurrently receiving either NBP or placebo therapy. Patients in the experimental group will receive intravenous infusion of 100ml NBP injection twice daily, while patients in the control group will receive intravenous infusion of 100ml saline solution twice daily. Each patient will receive continuous medication for 14 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients with a Cerebral Performance Category (CPC) Score of 1-2	The primary outcome is the proportion of patients with a Cerebral Performance Category (CPC) score of 1-2 at 6months after randomization in each group.	6 months

Collaborators and Investigators

• Sponsor: Tang Ziren

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: August 25, 2024
• First Submitted That Met QC Criteria: August 25, 2024
• First Posted (Actual): August 26, 2024

Study Record Updates

• Last Update Posted (Actual): April 11, 2025
• Last Update Submitted That Met QC Criteria: April 10, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Arrest; Physiological Effects of Drugs; Platelet Aggregation Inhibitors; Protective Agents; Neuroprotective Agents; 3-n-butylphthalide
• Other Study ID Numbers: 2023-11-30-4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD that underlie results in a publication
• IPD Sharing Time Frame: Starting 6 months after publication
• IPD Sharing Access Criteria: The de-identified survey data will be made available for research purposes by contacting the corresponding authors
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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