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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Efficacy and Safety of Propranolol for the Post-Stroke Pneumonia

Conditions
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Stroke, Vascular Accident, Intracranial Hemorrhages, Intracerebral Hemorrhage, Hemorrhagic Stroke, Stroke, Acute

Intervention / Treatment
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* Drug: Propranolol Hydrochloride
* Other: control group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years older and less than 80 years. Onset of new neurological deficits within≤24 hours at the time of randomization CT scan demonstrates supratentorial parenchymal hemorrhage and volume of hematoma≥10ml . Initial NIHSS score of 11 or greater and less than 25 scores. Initial GCS score (aggregate of verbal, eye, and motor response scores) of 8 or greater at time of enrollment. Admission without infection signs. Signed and dated informed consent by the subject, legally authorized representative, or surrogate obtained. Exclusion Criteria: 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. 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. Previous stroke or pre-onset motor disability (mRS≥1) Pregnancy or parturition within previous 30 days or active lactation. Use of beta blockers (propranolol, metoprolol, sotalol, carvedilol, bisoprolol, atenolol, esmolol, etc.) or reserpine within the last 30 days. Bronchial asthma or chronic obstructive pulmonary disease Cardiogenic shock or severe or acute heart failure. Degree II-III atrioventricular block or sinus bradycardia or heart rate ≤65/min. Known sensitivity to propranolol. Severe hepatic or renal insufficiency History of Malignancy Currently participating in other interventional clinical trials. Immunosuppressant therapy or known immunosuppression.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control group<br>Patients will receive usual care and drug use in hospital. | Other: control group<br>* Patients will receive usual care and drug use in hospital<br>|
| Experimental: Propranolol group<br>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<br>* Day of randomization: propranolol IV vp for 7 days after randomization<br>|

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, propranolol, infection, treatment