PROpranolol for Cerebral Hemorrhage-ASsociated pnEumonia (PRO-CHASE) (PRO-CHASE)

Efficacy and Safety of Propranolol for the Post-Stroke Pneumonia

Stroke-associated pneumonia (SAP) is a grave complication of stroke and one of the most important predictors for patients' poor outcomes. Stroke associated pneumoniaSAP and other infections limited the overall efficacy of stroke management. Increasing evidence suggests that sympathetic nervous system activity contributes to post post-stroke immunosuppression and emergence of infections. This study is designed to test the safety and efficacy of an adrenergic β receptor blocker propranolol in reducing SAP in hemorrhagic stroke patients, in a multi-center, randomized, open-labeled, end point-blinded, trial.

Study Overview

• Status: Recruiting
• Conditions: Stroke; Intracranial Hemorrhages; Stroke, Acute; Hemorrhagic Stroke; Intracerebral Hemorrhage; Vascular Accident
• Intervention / Treatment: Other: control group; Drug: Propranolol Hydrochloride

Detailed Description

This study will enroll 168 intracerebral hemorrhage patients who meet the inclusion criteria.

ICH patients meet the inclusion criteria will be randomly assigned at a 1:1 ratio into groups of standard treatment (blank-controlled), or propranolol hydrochloride injection .

Patients allocated to experimented group will be intravenously given initial dose at 5mg propranolol hydrochloride daily over a course of 7 consecutive days, The primary purpose of this study is to compare propranolol hydrochloride with standard treatment on reducing the 7-day risk of pneumonia when initiated within 24 hours of symptom onset in intracerebral hemorrhage.

Both intent analysis (ITT) and per-protocol (PP) were used for analysis.

• Study Type: Interventional
• Enrollment (Estimated): 168
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Fu-Dong Shi, MD; Phone Number: 8610-59976585; Email: fshi@tmu.edu.cn
• Study Contact Backup: Name: Xingquan Zhao, MD; Phone Number: +0086 13501031486; Email: zxq@vip.163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • Beijing Tiantan Hospital,Capital Medical University
      • Contact: Xingquan Zhao, MD
  • Gansu
    • Lanzhou, Gansu, China
      • Recruiting
      • Gansu Provincial Hospital
      • Contact: Shaopeng Peng, MD
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Recruiting
      • Zhangda Hospital Southeast University
      • Contact: Hong Wang, MD
  • Shaanxi
    • Weinan, Shaanxi, China
      • Recruiting
      • Weinan City Center hospital
      • Contact: Juntao Dang, MD
    • Xi'an, Shaanxi, China
      • Recruiting
      • Tangdu Hospital,Air Force Medical University
      • Contact: Yan Qu, MD
    • Xianyang, Shaanxi, China
      • Recruiting
      • Xianyang hospital affliated of Yan'an University
      • Contact: Zengqiang Liu, MD
  • Tianjin
    • Tianjin, Tianjin, China
      • Recruiting
      • Tianjin Third Central Hospital
      • Contact: Jing Zhang, MD
    • Tianjin, Tianjin, China
      • Recruiting
      • Tianjin Huanhu Hospital
      • Contact: Jialing Wu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18 years older and less than 80 years.
2. Onset of new neurological deficits within≤24 hours at the time of randomization
3. CT scan demonstrates supratentorial parenchymal hemorrhage and volume of hematoma≥10ml .
4. Initial NIHSS score of 11 or greater and less than 25 scores.
5. Initial GCS score (aggregate of verbal, eye, and motor response scores) of 8 or greater at time of enrollment.
6. Admission without infection signs.
7. Signed and dated informed consent by the subject, legally authorized representative, or surrogate obtained.

Exclusion Criteria:

1. Subjects is considered a candidate for immediate surgical intervention by the neurosurgery service, including surgical evacuation of hematoma, decompressive craniectomy, minimally invasive aspiration of hematoma, and ventricular shunt or external ventricular drainage for intracerebral hemorrhage into the ventricle.
2. Patients with primary intraventricular hemorrhage or cerebral hemorrhage due to a definite cause, such as trauma, vascular malformation, aneurysm, coagulopathy, anticoagulant or antiplatelet drugs, thrombolytic therapy, post-infarction hemorrhagic transformation, hematologic disease, moyamoya disease, primary or metastatic tumor, venous sinus thrombosis, vasculitis, etc.
3. Previous stroke or pre-onset motor disability (mRS≥1)
4. Pregnancy or parturition within previous 30 days or active lactation.
5. Use of beta blockers (propranolol, metoprolol, sotalol, carvedilol, bisoprolol, atenolol, esmolol, etc.) or reserpine within the last 30 days.
6. Bronchial asthma or chronic obstructive pulmonary disease
7. Cardiogenic shock or severe or acute heart failure.
8. Degree II-III atrioventricular block or sinus bradycardia or heart rate ≤65/min.
9. Known sensitivity to propranolol.
10. Severe hepatic or renal insufficiency
11. History of Malignancy
12. Currently participating in other interventional clinical trials.
13. Immunosuppressant therapy or known immunosuppression.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control group; Patients will receive usual care and drug use in hospital.	Other: control group; Patients will receive usual care and drug use in hospital
Experimental: Propranolol group; Propranolol hydrochloride will be administered intravenously via pump at a initial dose of 5mg/day over a course of 7 consecutive days after randomization.	Drug: Propranolol Hydrochloride; Day of randomization: propranolol IV vp for 7 days after randomization

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of stroke-associated pneumonia	Stroke-associated pneumonia diagnosed in accordance to a defined algorithm.	up to 7days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Event (AE)	Per protocol Adverse Event (AE), Adverse Reaction (AR), Serious Adverse Event / Reaction (SAE / SAR), and Suspected Unexpected Serious Adverse Reactions (SUSAR)	up to 90 days
Clinical improvement	Modified Rankin Scale （mRS，0-6 scores, poor outcome defined as mRS≥4）are used to describe the clinical improvement at baseline, 7days, 14days, 30days and 90days.	up to 90 days
Change in immunology function [ Time Frame: up to 7 days ]（ONLY patients recruited from Beijing Tiantan hospital and Tangdu Hospital, Air Force Medical University will receive this evaluation）	Use the flow cytometry to measure the change of ratio and number of CD4+、CD8+、NK 、B cells at baseline, 3 days, 7 days	up to 7 days
Spleen volume [ Time Frame: up to 7 days ] （ONLY patients recruited from Beijing Tiantan hospital and Tangdu Hospital, Air Force Medical University will receive this evaluation）	Spleen volume calculated based on Abdominal CT.	up to 7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total mortality	Total mortality	up to 90 days
Disability	Disability is defined as modified Rankin Scale≥3	up to 90 days

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2023
• Primary Completion (Estimated): July 3, 2024
• Study Completion (Estimated): July 3, 2025

Study Registration Dates

• First Submitted: June 2, 2022
• First Submitted That Met QC Criteria: June 10, 2022
• First Posted (Actual): June 15, 2022

Study Record Updates

• Last Update Posted (Estimated): November 8, 2023
• Last Update Submitted That Met QC Criteria: November 6, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: treatment; Stroke; infection; propranolol
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Stroke; Pneumonia; Hemorrhage; Intracranial Hemorrhages; Cerebral Hemorrhage; Hemorrhagic Stroke; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Propranolol
• Other Study ID Numbers: KY-2022-05-07-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The study protocol,statistical analysis plan(SAP),informed consent form(ICF),clinical study report(CSR),analytic code will be shared with other researchers.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; 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