Clinical trial NCT05419193: PROpranolol for Cerebral Hemorrhage-ASsociated pnEumonia (PRO-CHASE)
Official title: Efficacy and Safety of Propranolol for the Post-Stroke Pneumonia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stroke
Vascular Accident
Intracranial Hemorrhages
Intracerebral Hemorrhage
Hemorrhagic Stroke
Stroke, Acute
Keywords: Stroke
propranolol
infection
treatment
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
First posted: 2022-06-15
Enrollment: 168
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of stroke-associated pneumonia
timeFrame: up to 7days
Secondary outcomes:
measure: Clinical improvement
timeFrame: up to 90 days
measure: 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）
timeFrame: up to 7 days
measure: 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）
timeFrame: up to 7 days
measure: Adverse Event (AE)
timeFrame: up to 90 days
Other outcomes:
Locations:
city: Lu'an
country: China
facility: Lu'an Hospital of Traditional Chinese Medicine
state: Anhui
city: Beijing
country: China
facility: Beijing Tiantan Hospital,Capital Medical University
state: Beijing
city: Changzhou
country: China
facility: Third Affiliated Hospital, Soochow University
state: Jiangsu
city: Weinan
country: China
facility: Weinan City Center hospital
state: Shaanxi
city: Xi'an
country: China
facility: Tangdu Hospital,Air Force Medical University
state: Shaanxi
city: Xi'an
country: China
facility: Xi'an Central Hospital
state: Shaanxi
city: Xianyang
country: China
facility: Qianxian People's Hospital
state: Shaanxi
city: Xianyang
country: China
facility: The First People' Hospital of Xian Yang
state: Shaanxi
city: Xianyang
country: China
facility: Xianyang hospital affliated of Yan'an University
state: Shaanxi
city: Weihai
country: China
facility: The 970th Hospital of the Chinese People's Liberation Army (Weihai Branch)
state: Shandong
city: Yantai
country: China
facility: The 970th Hospital of the Chinese People's Liberation Army (Yantai Branch)
state: Shandong
city: Tianjin
country: China
facility: Tianjin Huanhu Hospital
state: Tianjin
Study officials:
References: