A Randomized, Blank-controlled, Open Label Study of the Safety and Efficacy of Propranolol in Reducing Stroke Associated Pneumonia and Urinary Tract Infection
试验速览
- 阶段
- 2 期
- 入组人数
- 45
- 试验地点
- 2
- 主要终点
- Incidence of pneumonia
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 60 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: 60 years older and less than 90 years.
- •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.
- •Clinical signs consistent with the diagnosis of stroke, including impairment of language, motor function, cognition, and/or gaze, vision, or neglect.
- •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.
- •MRI or CT scan confirmed stroke.
- •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.
- •TOAST: Large-artery atherosclerosis.
- •Signed and dated informed consent by the subject, legally authorized representative, or surrogate obtained.
排除标准
- •Time of symptom onset that cannot be reliably assessed.
- •Subjects considered as candidates for immediate surgical intervention by the neurosurgery service.
- •Pregnancy or parturition within previous 30 days or active lactation.
- •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.
- •Use of beta blockers (propranolol, metoprolol, sotalol, carvedilol, bisoprolol, atenolol, esmolol) or antibiotics within 30 days.
- •Use of reserpine within the last 30 days.
- •Pre-stroke dementia or disability.
- •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>
- •Severe liver, kidney disease, or malignancy, life expectancy is less than 14 days.
- •Bronchial asthma or COPD.
- •Cardiogenic shock.
- •Severe or acute heart failure.
- •Degree II-III atrioventricular block.
- •Sinus bradycardia (heart rate ≤75/min).
- •Known anergic to propranolol or amoxicillin.
- •Current participation in other interventional clinical trials.
- •Immunosuppressant therapy or known immunosuppression.
- •Inability to undergo neuroimaging with magnetic resonance.
研究组 & 干预措施
Oropranolol group
Propranolol will be administered at a dose of 10mg*3/day over a course of 7 consecutive days after stroke onset.
干预措施: Propranolol (Drug)
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.
干预措施: Propranolol (Drug)
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.
干预措施: Ceftriaxone (Drug)
结局指标
主要结局
Incidence of pneumonia
时间窗: Up to 7 days
Stroke-associated pneumonia diagnosed in accordance to a defined algorithm.
次要结局
- Assessment of clinical outcome by National Institute of Healthy Stroke Scale(Up to 90 days)
- Alterations of spleen volume(Up to 7 days)
- Concentration of soluble protein in blood and bronchoalveolar lavage fluid(Up to 7 days)
- Assessment of clinical outcome by modified Barthel Index(Up to 90 days)
- Incidence of sepsis(Up to 14 days)
- Counts of lymphocytes in blood(Up to 7 days)
- Assessment of clinical outcome by modified Rankin Scale(Up to 90 days)
- Assessment of clinical outcome by Glasgow Coma Scale(Up to 90 days)
- Incidence of urinary tract infection(Up to 14 days)
- Single cell sequencing results of immune cells from blood and bronchoalveolar lavage fluid(Up to 7 days)
研究者
Fu-Dong Shi
Professor of Immunology, Neurologist-in-Chief
Beijing Tiantan Hospital