Oral Hygiene and Prophylactic Antibiotics to Prevent Intracerebral Hemorrhage Associated Pneumonia

NCT ID: NCT07311343

Last Updated: 2025-12-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE4

Total Enrollment

440 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-01-01

Study Completion Date

2027-10-31

Brief Summary

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Project Name:

Randomized Controlled Clinical Study on oral hygiene and prophylactic antibiotics to prevent Intracerebral Hemorrhage associated pneumonia

Research Objectives:

To evaluate the effectiveness, safety and health economics value of enhanced oral hygiene combined with antibiotics in preventing post-cerebral hemorrhage pneumonia.

1. To clarify the effectiveness of enhanced oral hygiene combined with antibiotics in preventing post-cerebral hemorrhage pneumonia.
2. To clarify the safety of enhanced oral hygiene combined with antibiotics in preventing post-cerebral hemorrhage pneumonia.
3. To clarify the health economics value of low-intensity enhanced oral hygiene combined with antibiotics in preventing post-cerebral hemorrhage pneumonia.

Research Design:

Research Type: Multicenter, Randomized, Controlled, Open Label, Blinded Endpoint Research Design Research Hypothesis: Intensive oral hygiene combined with antibiotic treatment is beneficial in reducing the incidence of pulmonary infections related to cerebral hemorrhage.

Detailed Description

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Research Background:

The era of evidence-based medicine has been entered. For acute ischemic stroke within the 4.5-hour time window, intravenous thrombolysis, mechanical thrombectomy within 24 hours of onset, and stroke units all have clear evidence-based medical support for their intervention methods. However, for cerebral hemorrhage, which has higher disability and mortality rates, treatment methods currently lack evidence-based medical support, with management more often being supportive. In this context, exploring new targets, methods, and strategies to improve the prognosis of cerebrovascular diseases has become a hot topic in global research.

Stroke-associated pneumonia (SAP) is one of the most common complications after stroke. Substantial evidence shows that the occurrence of SAP not only increases patient length of hospital stay and medical expenses but also significantly elevates the risk of death and severe disability post-stroke. Based on data from the China National Stroke Registry (CNSR), the composition and distribution of various complications after cerebral infarction and cerebral hemorrhage in Chinese patients were first systematically reported. Among them, SAP is the most common complication for both major stroke subtypes: cerebral infarction and cerebral hemorrhage. Concurrently, it was also found that SAP not only increases the risk of adverse stroke prognosis but is also an important risk factor for the increase of various non-pneumonia complications. For example, in the sub-cohort of acute cerebral infarction patients (N=14,702), the occurrence of SAP increased the risk of gastrointestinal bleeding by 8-fold (adjusted OR=8.35; 95% CI=6.27-11.1; P\<0.001), pressure ulcers by 5-fold (OR=5.31; 95% CI=3.39-8.31; P\<0.001), deep vein thrombosis by 4-fold (OR=4.27; 95% CI=2.41-7.59; P\<0.001), symptomatic epilepsy by 4-fold (OR=3.96; 95% CI=2.67-5.88; P\<0.001), urinary tract infection by 3-fold (OR=3.34; 95% CI=2.73-4.10; P\<0.001), atrial fibrillation by 3-fold (OR=3.17; 95% CI=2.58-3.90; P\<0.001), and stroke recurrence by 2-fold (OR=2.65; 95% CI=2.07-3.40; P\<0.001).

The same phenomenon was also confirmed in the cerebral hemorrhage cohort (N=5,221). The effective prevention and control of SAP will become a new target for improving stroke prognosis, as clearly reflected in multiple domestic and international expert consensuses and guidelines on SAP.

Similar related studies have been conducted abroad. In 2015, the UK STROKE-INF study, for patients hospitalized within 48 hours after stroke onset, administered prophylactic antibiotics for 7 days plus standard stroke ward care or standard stroke ward care alone, finally including 1,217 patients from 37 units (615 in the antibiotic group, 602 in the control group). No difference was found in the diagnosis of post-stroke pneumonia between the two groups (101 of 615 patients \[16%\] in the antibiotic treatment group vs. 91 of 602 patients \[15%\] in the non-antibiotic treatment group; adjusted OR = 1.01 \[95% CI 0.61-1.68\], p = 0.957). In 2015, the Dutch PASS study randomly assigned acute stroke patients in a 1:1 ratio to an antibiotic treatment group (ceftriaxone) or a non-antibiotic treatment group (control) within 24 hours after onset. The control group received standardized stroke treatment; the ceftriaxone group received standardized treatment plus intravenous application of 2g ceftriaxone once daily for 4 days. Finally, 2,538 patients were included for treatment analysis (ceftriaxone group: 1,268; control group: 1,270). The study results showed that prophylactic use of ceftriaxone was safe, mainly manifested by a significantly lower incidence of urinary tract infections in the ceftriaxone group, with no significant difference in the incidence of infections at other sites between the two groups. Prophylactic ceftriaxone did not affect the distribution of 3-month modified Rankin Scale (mRS) scores (OR = 0.95 \[95% CI 0.81-1.09\], p = 0.46). Both these trials yielded negative results. This study aims to explore the relationship between the preventive use of antibiotics combined with oral care and the incidence of SAP in the Chinese population.

Research Objectives:

To clarify the effectiveness of enhanced oral hygiene combined with antibiotics in preventing pneumonia after cerebral hemorrhage.

To clarify the safety of enhanced oral hygiene combined with antibiotics in preventing pneumonia after cerebral hemorrhage.

To clarify the health economics value of enhanced oral hygiene combined with antibiotics in preventing pneumonia after cerebral hemorrhage.

Conditions

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Hemorrhage Pneumonia

Keywords

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Cerebral hemorrhage Stroke Associated Pneumonia oral care prophylactic antibiotics effectiveness

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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enhanced oral care combined with prophylactic antibiotics

After randomization, immediate intensive oral hygiene treatment (chlorhexidine 20ml, three times a day) combined with antibiotics (ceftazidime 1g, every 8 hours) was given on the basis of conventional standard treatment, and the treatment course was 3 days.

Group Type ACTIVE_COMPARATOR

wether apply enhanced oral care combined with prophylactic antibiotics

Intervention Type BIOLOGICAL

Intervention group: After randomization, immediate intensive oral hygiene treatment (chlorhexidine 20 ml, three times a day) combined with antibiotics (ceftazidime 1 g, every 8 hours) was administered on the basis of the conventional standard treatment, and the treatment lasted for 3 days; Control group: Conventional standard treatment combined with routine oral care (normal saline 20 ml, twice a day), and detailed records were made of the specific measures of patient oral care, including the selection of cleaning solution and frequency.

conventional standard treatment combined with conventional oral care

Conventional standard treatment combined with routine oral care (20 ml of normal saline twice a day), and detailed records were made of the specific measures of the patients' oral care, including the selection of the cleaning solution and the frequency.

Group Type EXPERIMENTAL

wether apply enhanced oral care combined with prophylactic antibiotics

Intervention Type BIOLOGICAL

Intervention group: After randomization, immediate intensive oral hygiene treatment (chlorhexidine 20 ml, three times a day) combined with antibiotics (ceftazidime 1 g, every 8 hours) was administered on the basis of the conventional standard treatment, and the treatment lasted for 3 days; Control group: Conventional standard treatment combined with routine oral care (normal saline 20 ml, twice a day), and detailed records were made of the specific measures of patient oral care, including the selection of cleaning solution and frequency.

Interventions

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wether apply enhanced oral care combined with prophylactic antibiotics

Intervention group: After randomization, immediate intensive oral hygiene treatment (chlorhexidine 20 ml, three times a day) combined with antibiotics (ceftazidime 1 g, every 8 hours) was administered on the basis of the conventional standard treatment, and the treatment lasted for 3 days; Control group: Conventional standard treatment combined with routine oral care (normal saline 20 ml, twice a day), and detailed records were made of the specific measures of patient oral care, including the selection of cleaning solution and frequency.

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

1. Age 18-80 years old;
2. Spontaneous intracerebral hemorrhage;
3. Supratentorial intracerebral hemorrhage (ICH);
4. Hematoma volume \< 30 ml (calculated by ABC/2 method);
5. Glasgow Coma Scale score ≥ 9 at randomization;
6. Time from onset to randomization ≤ 72 hours;
7. Spontaneous intracerebral hemorrhage-associated pneumonia score (ICH-APS) ≥ 8;
8. Informed consent from the patient and/or their family.

Exclusion Criteria

1. Secondary intracerebral hemorrhage, such as that resulting from cerebral aneurysms, cerebral arteriovenous malformations, brain tumors, cerebral venous system thrombosis, antithrombotic therapy (antiplatelet, anticoagulant therapy, etc.), hemorrhagic transformation after cerebral infarction, hematological diseases, etc.
2. The patient's clinical symptoms and signs suggest signs of brain herniation, such as progressive decline in consciousness level, weakened or absent pupillary light reflex.
3. Obvious signs of pneumonia already exist, such as fever, persistent cough or yellow purulent sputum, and imaging examinations (chest X-ray or chest CT) suggest signs of pneumonia; two consecutive measurements of body temperature ≥ 37.5℃, or one measurement of body temperature ≥ 38.0℃.
4. A history of severe cardiovascular disease, meeting any of the following: 1) Heart failure (New York Heart Association functional class ≥ III); 2) Unstable angina within 3 months; 3) Any supraventricular or ventricular arrhythmia requiring treatment; 4) Prolonged QTc interval considered clinically significant by the investigator (reference range: \> 450ms for men, \> 470ms for women) (Note: QTc interval must be calculated according to Fridericia's formula); 5) Complete atrioventricular block and left or right bundle branch block requiring treatment; 6) Acute myocardial infarction or interventional treatment within 1 month; high-risk patients with chronic arrhythmia, such as sick sinus syndrome, second or third-degree atrioventricular block, bradycardia-related syncope without pacemaker installation, etc.
5. Diagnosed with severe active liver disease, such as acute hepatitis, chronic active hepatitis, liver cirrhosis, etc.; or ALT or AST \> 3 times the upper limit of normal.
6. Severe renal insufficiency: such as patients undergoing dialysis, or diagnosed with severe active kidney disease, etc., or creatinine clearance rate \< 50 mL/min.
7. Other severe diseases that lead to an expected lifespan of less than 1 year.
8. Patients scheduled for surgical intervention before the first administration, including but not limited to hematoma evacuation (including minimally invasive and conventional surgery), decompressive craniectomy, hematoma aspiration, and external ventricular drainage.
9. Patients unable to understand the research procedures and/or complete follow-up due to mental illness, cognitive impairment, emotional disorders, etc.
10. Pregnant or lactating women.
11. Participation in other clinical studies within 3 months or currently participating in other clinical studies.
12. Known allergy to cephalosporins, penicillins, or chlorhexidine compound mouthwash.

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Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Beijing Tiantan Hospital

OTHER

Sponsor Role lead

Responsible Party

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guojunping

Associate Chief Nurse

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Junping Guo

Role: PRINCIPAL_INVESTIGATOR

Beijing Tiantan Hospital

Locations

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Beijing Tiantan Hospital

Beijing, Beijing Municipality, China

Site Status

Countries

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China

Central Contacts

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Xue Sun

Role: CONTACT

Phone: 86+13521769614

Email: [email protected]

Qixuan Guan

Role: CONTACT

Phone: 86+18612572388

Email: [email protected]

Facility Contacts

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Junping Guo

Role: primary

References

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Other Identifiers

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KY2025-105-03

Identifier Type: -

Identifier Source: org_study_id