Propranolol on Post Stroke Immune Status and Infection

NCT ID: NCT05375240

Last Updated: 2022-05-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-06-30

Study Completion Date

2024-06-30

Brief Summary

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Stroke-associated pneumonia (SAP) is one of the important risk factors influencing poor outcomes and death in stroke patients. Over the past two decades, accumulating evidence suggests that post-stroke brain injury mobilizes the adrenergic system, which induces post-stroke immunosuppression and SAP. This study is designed to test the safety and efficacy of an adrenergic β-receptor blocker, propranolol, with or without combination of antibiotics, in reducing SAP in stroke patients. The underlying immune mechanisms will be investigated.

Detailed Description

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Stroke patients meeting the inclusion criteria will be randomly assigned at a 1:1:1 ratio into groups of standard treatment (blank-controlled), propranolol, or propranolol + ceftriaxone.

Patients will be given 10.0mg\*3/day oral/nil propranolol alone or combined with 2.0g/day intravenous ceftriaxone over the course of 7 consecutive days. Neurological functions of these patients will be assessed at the baseline, day 7, 14, 30, and 90 after randomization. Head magnetic resonance imaging (MRI) will be performed at baseline and 7 days after randomization. Chest computed tomography (CT) will be performed within 7 days following randomization. Abdomen CT will be performed simultaneously with CT chest to evaluate spleen volume. For patients requiring acute endotracheal intubation upon admission, bronchoalveolar lavage fluid will be harvested at baseline and 7 days post-randomization. For all patients, 15 mL intravenous blood will be collected at baseline, days 3 and 7 after randomization. Bronchoalveolar lavage fluid and blood will be used to explore the peripheral and pulmonary immune status of patients. Urinary tract infection will be evaluated within 14 days based on routine urine test and bacterial culture.

Conditions

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Stroke Cerebrovascular Disorders Ischemic Stroke Brain Diseases Central Nervous System Diseases Nervous System Diseases Cardiovascular Diseases Propranolol Beta Blocker Molecular Mechanisms of Pharmacological Action Immunologic Factors Physiological Effects of Drugs

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Blank-control group

Patients will receive standard treatment.

Group Type NO_INTERVENTION

No interventions assigned to this group

Oropranolol group

Propranolol will be administered at a dose of 10mg\*3/day over a course of 7 consecutive days after stroke onset.

Group Type EXPERIMENTAL

Propranolol

Intervention Type DRUG

Propranolol will be given at a dose of 10 mg orally, 3 times per day, for 7 consecutive days after stroke onset.

Propranolol + ceftriaxone group

Propranolol will be administered at a dose of 10mg\*3/day combined with 2g/day ceftriaxone over a course of 7 consecutive days after stroke onset.

Group Type EXPERIMENTAL

Propranolol

Intervention Type DRUG

Propranolol will be given at a dose of 10 mg orally, 3 times per day, for 7 consecutive days after stroke onset.

Ceftriaxone

Intervention Type DRUG

Intravenously 2.0g/day for 7 consecutive days.

Interventions

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Propranolol

Propranolol will be given at a dose of 10 mg orally, 3 times per day, for 7 consecutive days after stroke onset.

Intervention Type DRUG

Ceftriaxone

Intravenously 2.0g/day for 7 consecutive days.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Age: 60 years older and less than 90 years.
2. Onset of new neurological deficits within 24 hours at the time of randomization and propranolol treatment can be initiated within 24 hours of symptom onset.
3. Clinical signs consistent with the diagnosis of stroke, including impairment of language, motor function, cognition, and/or gaze, vision, or neglect.
4. Initial NIHSS score of 11 or greater or Total GCS score (aggregate of verbal, eye, and motor response scores) of 5 or greater and no more than 12 at time of enrollment.
5. MRI or CT scan confirmed stroke.
6. Inability to tolerate normal diet or fluids because of: a. impaired consciousness levels; b. failed clinical bedside swallowing assessment performed by a trained and qualified assessor; c. "nil orally" orders, nasogastric tubes, modified diet or requiring compensatory feeding techniques.
7. TOAST: Large-artery atherosclerosis.
8. Signed and dated informed consent by the subject, legally authorized representative, or surrogate obtained.

Exclusion Criteria

1. Time of symptom onset that cannot be reliably assessed.
2. Subjects considered as candidates for immediate surgical intervention by the neurosurgery service.
3. Pregnancy or parturition within previous 30 days or active lactation.
4. Coagulation disorders (platelet count less than 50x109/L, elevated baseline APTT or INR\>1.3) or use of anti-coagulant drugs within the last 24 hours.
5. Use of beta blockers (propranolol, metoprolol, sotalol, carvedilol, bisoprolol, atenolol, esmolol) or antibiotics within 30 days.
6. Use of reserpine within the last 30 days.
7. Pre-stroke dementia or disability.
8. Admission with any of following signs: 1). Fever\>38℃; 2). Signs of pneumonia in chest CT scan; 3). White blood cell count\>12000 or \<4000 /μL; 4). Cough, sputum or dyspnea; 5). Respiratory rate\>25.
9. Severe liver, kidney disease, or malignancy, life expectancy is less than 14 days.
10. Bronchial asthma or COPD.
11. Cardiogenic shock.
12. Severe or acute heart failure.
13. Degree II-III atrioventricular block.
14. Sinus bradycardia (heart rate ≤75/min).
15. Known anergic to propranolol or amoxicillin.
16. Current participation in other interventional clinical trials.
17. Immunosuppressant therapy or known immunosuppression.
18. Inability to undergo neuroimaging with magnetic resonance.
Minimum Eligible Age

60 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Tianjin Medical University General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Fu-Dong Shi

Professor of Immunology, Neurologist-in-Chief

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Beijing Tiantan Hospital

Beijing, , China

Site Status

Tianjin Medical University General Hospital

Tianjin, , China

Site Status

Countries

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China

Central Contacts

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Fu-Dong Shi, Ph.D

Role: CONTACT

+8615822011530

Facility Contacts

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Fu-Dong Shi, MD,PhD

Role: primary

Fu-Dong Shi, MD,PhD

Role: primary

Other Identifiers

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IRB2022-YX-001

Identifier Type: -

Identifier Source: org_study_id

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