PROpranolol for Cerebral Hemorrhage-ASsociated pnEumonia (PRO-CHASE)

Sponsor

Beijing Tiantan Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05419193

Collaborator

(none)

926

Enrollment

Location

Arms

Anticipated Duration (Months)

25.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Stroke-associated pneumonia (SAP) is a grave complication of stroke and one of the most important predictors for patients' poor outcomes. Stroke associated pneumonia and other infections limit the overall efficacy of stroke management. Increasing evidence suggests that sympathetic nervous system activity contributes to post stroke immunosuppression and emergence of infections. This study is designed to test the safety and efficacy of an adrenergic β receptor blocker propranolol in reducing SAP in hemorrhagic stroke patients, in multi-center, randomized, placebo controlled, double blinded fashion.

Condition or Disease	Intervention/Treatment	Phase
Stroke Vascular Accident Intracranial Hemorrhages Intracerebral Hemorrhage Hemorrhagic Stroke Stroke, Acute	Drug: Propranolol Hydrochloride Drug: Propranolol Hydrochloride and ceftriaxone Other: control group	Phase 3

Detailed Description

This study will enroll 926 intracerebral hemorrhage patients who meet the inclusion criteria.

ICH patients meet 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 allocated to experimented group will be intravenously given 5mg propranolol daily alone or plus 2 g/day intravenous ceftriaxone over a course of 7 consecutive days, The primary purpose of this study is to compare propranolol or placebo on reducing the 7-day risk of pneumonia when initiated within 24 hours of symptom onset in intracerebral hemorrhage.

Both intent analysis (ITT) and per-protocol (PP) were used for analysis.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

926 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Parallel AssignmentParallel Assignment

Masking:

Single (Outcomes Assessor)

Masking Description:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Efficacy and Safety of Propranolol for the Post-Stroke Pneumonia

Anticipated Study Start Date :

Jul 3, 2022

Anticipated Primary Completion Date :

Jul 3, 2024

Anticipated Study Completion Date :

Jul 3, 2025

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Control group Patients will receive usual care and drug use in hospital.	Other: control group Patients will receive usual care and drug use in hospital
Experimental: Propranolol group Propranolol will be administered intravenously via pump at a dose of 5mg/day over a course of 7 consecutive days after randomization.	Drug: Propranolol Hydrochloride Day of randomization: propranolol IV vp for 7 days after randomization
Experimental: Propranolol + ceftriaxone group Propranolol intravenously via pump at a dose of 5mg/day for 7 consecutive days Ceftriaxone intravenously at a dose of 2g/day for 7 consecutive days	Drug: Propranolol Hydrochloride and ceftriaxone Day of randomization: propranolol IV vp combined with ceftriaxone IV for 7 days after randomization

Arm

Intervention/Treatment

Placebo Comparator: Control group

Patients will receive usual care and drug use in hospital.

Other: control group

Patients will receive usual care and drug use in hospital

Experimental: Propranolol group

Propranolol will be administered intravenously via pump at a dose of 5mg/day over a course of 7 consecutive days after randomization.

Drug: Propranolol Hydrochloride

Day of randomization: propranolol IV vp for 7 days after randomization

Experimental: Propranolol + ceftriaxone group

Propranolol intravenously via pump at a dose of 5mg/day for 7 consecutive days Ceftriaxone intravenously at a dose of 2g/day for 7 consecutive days

Drug: Propranolol Hydrochloride and ceftriaxone

Day of randomization: propranolol IV vp combined with ceftriaxone IV for 7 days after randomization

Outcome Measures

Primary Outcome Measures

Incidence of stroke-associated pneumonia [up to 7days]
Stroke-associated pneumonia diagnosed in accordance to a defined algorithm.

Secondary Outcome Measures

Assessment of clinical outcome by National Institute of Healthy Stroke Scale [up to 90 days]
National Institute of Healthy Stroke Scale(0-42 score),higher scores mean a worse outcome.
Assessment of clinical outcome by modified Barthel Index [up to 90 days]
Modified Barthel Index（0-100 score),higher scores mean a better outcome.
Assessment of clinical outcome by modified Rankin Scale [up to 90 days]
Modified Rankin Scale(0-5 score),higher scores mean a worse outcome.
Assessment of clinical outcome by Glasgow Coma Scale [up to 90 days]
Glasgow Coma Scale(0-15),higher scores mean a better outcome.
Assessment of clinical outcome by Quality of Life (EuroQol EQ-5D scale) [up to 90 days]
Further efficacy exploratory analysis:Quality of Life (EuroQol EQ-5D scale). We will use the EQ-5D-5L scale to evaluate the quality of life. EQ-5D-5L is a standardized instrument for measuring generic health status. It has been widely used in population health surveys, clinical studies, economic evaluation and in routine outcome measurement in the delivery of operational healthcare. The EQ-5D-5L has five domain scales (mobility, self-care, usual activities, pain and discomfort, and anxiety and depression) and five levels for each domain.
Incidence of post-stroke pneumonia [up to 14days]
Post-stroke pneumonia is diagnosed by clinician
Incidence of urinary tract infection [up to 14 days]
Urinary tract infection is diagnosed within defined criteria
Incidence of sepsis [up to 14 days]
Sepsis is diagnosed with defined criteria.
Incidence of elevated cardiac troponin I(E-cTnI) [up to 14 days]
Occurrence of elevated cardiac troponin I(cTnI) at 14 days or at discharge if sooner
Incidence of gastrointestinal hemorrhage(GH) [up to 14 days]
Occurrence of gastrointestinal hemorrhage at 14 days or at discharge if sooner
Adverse Event (AE) [up to 90 days]
Per protocol Adverse Event (AE), Adverse Reaction (AR), Serious Adverse Event / Reaction (SAE / SAR), and Suspected Unexpected Serious Adverse Reactions (SUSAR)
Total hospital costs [up to 90 days]
Total hospital costs were counted as CNY
Length of stay in hospital [up to 90 days]
length of stay in hospital

Other Outcome Measures

Total mortality [up to 90 days]
Total mortality
Disability [up to 90 days]
Disability is defined as modified Rankin Scale≥3

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 60 years older and no more than 90 years.
Onset of new neurological deficits within≤24 hours at the time of randomization
CT scan demonstrates parenchymal hemorrhage.
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.
Unable to tolerate normal diet or fluids because of:
impaired consciousness levels.
failed clinical bedside swallowing assessment performed by a trained assessor.
"nil orally" orders, nasogastric tubes, modified diet or requiring compensatory feeding techniques.
Admission without infection signs. Signed and dated informed consent by the subject, legally authorized representative, or surrogate obtained.

Exclusion Criteria:

Time of symptom onset cannot be reliably assessed.
Subjects is considered a candidate for immediate surgical intervention by the neurosurgery service.
Pregnancy or parturition within previous 30 days or active lactation.
Use of beta blockers (propranolol, metoprolol, sotalol, carvedilol, bisoprolol, atenolol, esmolol, and etc.) or antibiotics within the last 30 days.
Use of reserpine within the last 30 days.
Pre-stroke dementia or disability.
With severe liver, kidney disease, or malignancy, life expectancy is less than 14 days.
Bronchial asthma or COPD.
Cardiogenic shock or severe or acute heart failure.
Degree II-III atrioventricular block or sinus bradycardia (heart rate ≤75/min).
Known sensitivity to propranolol.
Currently participating in other interventional clinical trials.
Immunosuppressant therapy or known immunosuppression.