Back to resultsPropranolol on Post Stroke Immune Status and Infection
Primary Purpose
Stroke, Cerebrovascular Disorders, Ischemic Stroke
Status
Not yet recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Propranolol
Ceftriaxone
Sponsored by
About this trial
This is an interventional treatment trial for Stroke focused on measuring Stroke, Propranolol, Infection, Treatment
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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>25.
- 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.
Sites / Locations
- Beijing Tiantan Hospital
- Tianjin Medical University General Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
No Intervention
Experimental
Experimental
Arm Label
Blank-control group
Oropranolol group
Propranolol + ceftriaxone group
Arm Description
Patients will receive standard treatment.
Propranolol will be administered at a dose of 10mg*3/day over a course of 7 consecutive days after stroke onset.
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.
Outcomes
Primary Outcome Measures
Incidence of pneumonia
Stroke-associated pneumonia diagnosed in accordance to a defined algorithm.
Secondary Outcome Measures
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.
Assessment of clinical outcome by modified Barthel Index
Modified Barthel Index（0-100 score),higher scores mean a better outcome.
Assessment of clinical outcome by modified Rankin Scale
Modified Rankin Scale(0-5 score),higher scores mean a worse outcome.
Assessment of clinical outcome by Glasgow Coma Scale
Glasgow Coma Scale(0-15),higher scores mean a better outcome.
Incidence of urinary tract infection
Urinary tract infection diagnosed with defined criteria.
Incidence of sepsis
Sepsis diagnosed with defined criteria.
Alterations of spleen volume
Spleen volume will be evaluated within 7 days via abdomen CT scan.
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.
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
Counts of lymphocytes in blood
Counts of lymphocytes will be evaluated by flow cytometry at baseline, day 3, and day 7 post stroke onset
Full Information
NCT ID
NCT05375240
First Posted
April 19, 2022
Last Updated
May 11, 2022
Sponsor
Tianjin Medical University General Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05375240
Brief Title
Propranolol on Post Stroke Immune Status and Infection
Official Title
A Randomized, Blank-controlled, Open Label Study of the Safety and Efficacy of Propranolol in Reducing Stroke Associated Pneumonia and Urinary Tract Infection
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
June 2022 (Anticipated)
Primary Completion Date
June 2024 (Anticipated)
Study Completion Date
June 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Tianjin Medical University General Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
Keywords
Stroke, Propranolol, Infection, Treatment
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
45 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Blank-control group
Arm Type
No Intervention
Arm Description
Patients will receive standard treatment.
Arm Title
Oropranolol group
Arm Type
Experimental
Arm Description
Propranolol will be administered at a dose of 10mg*3/day over a course of 7 consecutive days after stroke onset.
Arm Title
Propranolol + ceftriaxone group
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Propranolol
Intervention Description
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
Intervention Name(s)
Ceftriaxone
Intervention Description
Intravenously 2.0g/day for 7 consecutive days.
Primary Outcome Measure Information:
Title
Incidence of pneumonia
Description
Stroke-associated pneumonia diagnosed in accordance to a defined algorithm.
Time Frame
Up to 7 days
Secondary Outcome Measure Information:
Title
Assessment of clinical outcome by National Institute of Healthy Stroke Scale
Description
National Institute of Healthy Stroke Scale(0-42 score),higher scores mean a worse outcome.
Time Frame
Up to 90 days
Title
Assessment of clinical outcome by modified Barthel Index
Description
Modified Barthel Index（0-100 score),higher scores mean a better outcome.
Time Frame
Up to 90 days
Title
Assessment of clinical outcome by modified Rankin Scale
Description
Modified Rankin Scale(0-5 score),higher scores mean a worse outcome.
Time Frame
Up to 90 days
Title
Assessment of clinical outcome by Glasgow Coma Scale
Description
Glasgow Coma Scale(0-15),higher scores mean a better outcome.
Time Frame
Up to 90 days
Title
Incidence of urinary tract infection
Description
Urinary tract infection diagnosed with defined criteria.
Time Frame
Up to 14 days
Title
Incidence of sepsis
Description
Sepsis diagnosed with defined criteria.
Time Frame
Up to 14 days
Title
Alterations of spleen volume
Description
Spleen volume will be evaluated within 7 days via abdomen CT scan.
Time Frame
Up to 7 days
Title
Single cell sequencing results of immune cells from blood and bronchoalveolar lavage fluid
Description
Single cell sequencing of immune cells from blood and bronchoalveolar lavage fluid will be conducted at baseline and 7 days after stroke onset.
Time Frame
Up to 7 days
Title
Concentration of soluble protein in blood and bronchoalveolar lavage fluid
Description
Soluble proteins in blood and bronchoalveolar lavage fluid will be evaluated by O-link at baseline and 7 days after stroke onset
Time Frame
Up to 7 days
Title
Counts of lymphocytes in blood
Description
Counts of lymphocytes will be evaluated by flow cytometry at baseline, day 3, and day 7 post stroke onset
Time Frame
Up to 7 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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>25.
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Fu-Dong Shi, Ph.D
Phone
+8615822011530
Email
fshi@tmu.edu.cn
Facility Information:
Facility Name
Beijing Tiantan Hospital
City
Beijing
ZIP/Postal Code
100070
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fu-Dong Shi, MD,PhD
Facility Name
Tianjin Medical University General Hospital
City
Tianjin
ZIP/Postal Code
300052
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fu-Dong Shi, MD,PhD
12. IPD Sharing Statement
Plan to Share IPD
No
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Propranolol on Post Stroke Immune Status and Infection
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