Butylphthalide's Safety and Efficacy for Improving Neurological Function Prognosis in Patients With Cardiac Arrest (BNCA Trial)

Butylphthalide's Safety and Efficacy for Improving Neurological Function Prognosis in Patients With Cardiac Arrest (BNCA Trial): A Single-Center, Randomized, Double-Blind, Placebo-Controlled Study

Butylphthalide (NBP) is a neuroprotective medication capable of ameliorating neurological dysfunction induced by ischemia, hypoxia, and reperfusion injury in the brain. However, evidence regarding the improvement of neurological function prognosis in patients with return of spontaneous circulation (ROSC) after cardiac arrest (CA) by NBP is limited. This study aims to evaluate the safety and efficacy of NBP treatment in improving the neurological function prognosis of patients with ROSC after CA.The study will be a single-center, randomized, double-blind, placebo-controlled trial. The sample size is estimated to be 100 patients. Eligible patients will be randomly allocated in a 1:1 ratio to receive either NBP or placebo treatment daily for a duration of 14 days. The initial administration of NBP or placebo treatment will commence within 6 hours after ROSC following CA. The primary outcome is the proportion of patients with Cerebral Performance Category (CPC) scores of 1-2 at 90 days after randomization in each group. The primary safety outcome is the percentage of severe adverse events occurring during the 14-day treatment period. This trial will determine the efficacy of NBP in providing neuroprotective effects for patients with ROSC after CA.

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): 100
• Phase: Phase 4

Contacts and Locations

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

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100020
      • Recruiting
      • Beijing Chao-Yang Hospital
      • Contact: Xingsheng Wang, M.D.; Phone Number: +86 15265386100; Email: wangxingsheng1995@163.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. GCS scores ≤8 upon admission.
3. 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 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 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 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 CPC score of 1-2	The primary outcome is the proportion of patients with a CPC score of 1-2 at 90days after randomization in each group. Favourable: 1 means full recovery or mild disability, 2 means moderate disability but independent in activities of daily living (ADLs). Unfavourable: 3 means severe disability-Dependent in ADLs, 4 means persistent vegetive state, 5 means Death.	90 days

Collaborators and Investigators

• Sponsor: Tang Ziren

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: April 2, 2024
• First Submitted That Met QC Criteria: April 6, 2024
• First Posted (Actual): April 9, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 6, 2025
• Last Verified: February 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: 2024-3-22-8

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