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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Blank-control group | No Intervention | Patients will receive standard treatment. | |
| Oropranolol group | Experimental | Propranolol will be administered at a dose of 10mg*3/day over a course of 7 consecutive days after stroke onset. |
|
| Propranolol + ceftriaxone group | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Propranolol | Drug | Propranolol will be given at a dose of 10 mg orally, 3 times per day, for 7 consecutive days after stroke onset. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of pneumonia | Stroke-associated pneumonia diagnosed in accordance to a defined algorithm. | Up to 7 days |
| Measure | Description | Time Frame |
|---|---|---|
| Assessment of clinical outcome by National Institute of Healthy Stroke Scale | National Institute of Healthy Stroke Scale(0-42 score),higher scores mean a worse outcome. | Up to 90 days |
| Assessment of clinical outcome by modified Barthel Index |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Fu-Dong Shi, Ph.D | Contact | +8615822011530 | fshi@tmu.edu.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Tiantan Hospital | Beijing | 100070 | China |
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| Ceftriaxone | Drug | Intravenously 2.0g/day for 7 consecutive days. |
|
Modified Barthel Index(0-100 score),higher scores mean a better outcome.
| Up to 90 days |
| Assessment of clinical outcome by modified Rankin Scale | Modified Rankin Scale(0-5 score),higher scores mean a worse outcome. | Up to 90 days |
| Assessment of clinical outcome by Glasgow Coma Scale | Glasgow Coma Scale(0-15),higher scores mean a better outcome. | Up to 90 days |
| Incidence of urinary tract infection | Urinary tract infection diagnosed with defined criteria. | Up to 14 days |
| Incidence of sepsis | Sepsis diagnosed with defined criteria. | Up to 14 days |
| Alterations of spleen volume | Spleen volume will be evaluated within 7 days via abdomen CT scan. | Up to 7 days |
| Single cell sequencing results of immune cells from blood and bronchoalveolar lavage fluid | Single cell sequencing of immune cells from blood and bronchoalveolar lavage fluid will be conducted at baseline and 7 days after stroke onset. | Up to 7 days |
| Concentration of soluble protein in blood and bronchoalveolar lavage fluid | Soluble proteins in blood and bronchoalveolar lavage fluid will be evaluated by O-link at baseline and 7 days after stroke onset | Up to 7 days |
| Counts of lymphocytes in blood | Counts of lymphocytes will be evaluated by flow cytometry at baseline, day 3, and day 7 post stroke onset | Up to 7 days |
| Tianjin Medical University General Hospital | Tianjin | 300052 | China |
|
| ID | Term |
|---|---|
| D020521 | Stroke |
| D002561 | Cerebrovascular Disorders |
| D000083242 | Ischemic Stroke |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D002318 | Cardiovascular Diseases |
| D007239 | Infections |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| D011433 | Propranolol |
| D002443 | Ceftriaxone |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D002439 | Cefotaxime |
| D002505 | Cephacetrile |
| D002511 | Cephalosporins |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 | Amides |
| D013843 | Thiazines |
| D013457 | Sulfur Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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