Propranolol on Post Stroke Immune Status and Infection

Tianjin Medical University

Status and phase: Not yet enrolling; Phase 2

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

Treatments: Drug: Ceftriaxone; Drug: Propranolol

Study type: Interventional

Funder types: Other

Identifiers

NCT05375240

IRB2022-YX-001

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 45 estimated patients

Sex: All

Ages: 60 to 90 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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45 participants in 3 patient groups

Blank-control group

No Intervention group

Description:

Patients will receive standard treatment.

Oropranolol group

Experimental group

Description:

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

Treatment:

Drug: Propranolol

Propranolol + ceftriaxone group

Experimental group

Description:

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.

Treatment:

Drug: Ceftriaxone

Drug: Propranolol