Clinical trial NCT06358209: Safety and Efficacy of Ventricular Irrigation for Ventriculitis
Official title: Safety and Efficacy of Ventricular Irrigation for Ventriculitis: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Central Nervous System Infections
Keywords: Ventriculitis
Ventricular irrigation
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
Collaborators: name: Southern Medical University, China
name: First Affiliated Hospital of Zhejiang University
name: 904th Hospital of the Joint Logistics Support Force of the PLA
name: Shenzhen Second People's Hospital
name: First Affiliated Hospital of Wannan Medical College
name: Huashan Hospital
First posted: 2024-04-10
Enrollment: 310
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Ventriculitis is a severe infectious disease of the central nervous system with diverse etiologies. Currently, the treatment for ventriculitis is challenging, with poor prognosis. The mortality rate of ventriculitis is generally reported to be higher than 30%, with the highest reaching over 75%. Even among survivors, over 60% suffer from a variety of neurological sequelae, including cognitive impairment, gait disturbances, paralysis, behavioral disorders, and epilepsy.

Currently, treatments for ventriculitis recommended by guidelines primarily focus on the selection and administration of antibiotics, while the effects of surgical interventions have not been fully elucidated. In recent years, several studies have explored the use of ventricular irrigation in ventriculitis, indicating that ventricular irrigation techniques may accelerate the control of ventricular infection, mitigate damage to the central nervous system caused by infections, improve the prognosis of ventriculitis, and reduce complications such as hydrocephalus. However, current studies are still relatively scarce, and mostly case reports and retrospective studies. High-quality evidence is still lacking for the application of ventricular irrigation in ventriculitis.

This multicenter randomized controlled trial aims to explore the safety and effectiveness of ventricular irrigation compared to conventional treatment for severe ventriculitis, analyze the effectiveness of ventricular irrigation across different pathogen subgroups, and investigate independent risk factors for different prognostic states in patients with severe ventriculitis.

Detailed description: Ventriculitis is a severe infectious disease of the central nervous system with diverse etiologies. Ventriculitis is associated not only with community-acquired diseases but also, more importantly, with invasive clinical procedures, including craniotomy, external ventricular drainage (EVD), lumbar cistern drainage, V-P shunt, and deep brain stimulation, among others. Depending on the diagnostic criteria, the incidence of post-neurosurgery ventriculitis ranges from approximately 5% to 20%, with risk factors including age, prolonged placement of EVD, and intracranial hemorrhage. Besides, the pathogens leading to ventricular infection are also diverse, with the main pathogens including coagulase-negative Staphylococci, Staphylococcus aureus, Propionibacterium acnes, and Gram-negative bacilli.

The treatment for ventriculitis is challenging, with poor prognosis. Under currently widely adopted treatment strategies, the mortality rate of ventriculitis is generally reported to be higher than 30%, with the highest reaching over 75%. Even among survivors, over 60% suffer from a variety of neurological sequelae, including cognitive impairment, gait disturbances, paralysis, behavioral disorders, and epilepsy. This imposes significant burden on families and society. Therefore, how to further improve prognosis of ventriculitis, and reduce the mortality and disability rates, remains to be addressed.

Currently, treatments for ventriculitis recommended by guidelines primarily focus on the selection and administration of antibiotics, while the effects of surgical interventions have not been fully elucidated. As an infectious disease, surgical procedures such as irrigation and drainage have the potential to play a role in reducing infection and improving prognosis for ventriculitis.

In recent years, several studies have explored the use of ventricular irrigation in ventriculitis, indicating that ventricular irrigation techniques (including endoscopic ventricular irrigation and dual catheter irrigation techniques) via replacing saline and draining purulent cerebrospinal fluid (CSF), may accelerate the control of ventricular infection, mitigate damage to the central nervous system caused by infections, improve the prognosis of ventriculitis, and reduce complications such as hydrocephalus. However, current studies are still relatively scarce, and mostly case reports and retrospective studies. A prospective controlled study that included 33 patients with ventriculitis divided participants into groups receiving ventricular irrigation treatment and conventional treatment. The study results showed that compared to conventional treatment, ventricular irrigation resulted in higher mRS prognosis scores, shorter hospital stays, and the study also showed a trend towards reduced mortality in irrigation group. However, this study was limited by a small sample size, limited study endpoints and not strictly randomized. Currently, high-quality evidence is still lacking for the application of ventricular irrigation in ventriculitis.

Based on these considerations, this multicenter randomized controlled trial aims to explore the safety and effectiveness of ventricular irrigation compared to conventional treatment for severe ventriculitis, analyze the effectiveness of ventricular irrigation across different pathogen subgroups, and investigate independent risk factors for different prognostic states in patients with severe ventriculitis.

Eligibility criteria: Inclusion Criteria:

* Age 18-65 years old;
* CSF is purulent and white blood cell count over 1000×10\^6/L.
* Fever (\>38.0°C)
* Meet at least one of the following: 1. Patient has organism(s) identified from CSF by a culture or non-culture based microbiologic testing method; 2. Cranial CT or MRI indicating intraventricular floccule or pus.
* With consent form

Exclusion Criteria:

* With GCS score of 3
* With unstable vital signs such as no spontaneous breathing and blood pressure maintenance drugs
* With serious infections in other parts of the body
* With propensity for bleeding, including history of hemophilia, anticoagulant medication, and abnormal coagulation upon admission
* Pregnancy

Primary outcomes:
measure: Clinical cure rate
timeFrame: 4 weeks after enrollment
Secondary outcomes:
measure: GOSE
timeFrame: At discharge and within 6 months after diagnosis
measure: CSF test results
timeFrame: At 8th day after enrollment, and within 1 week before discharge
measure: Cranial CT or MRI indicating
timeFrame: At 8th day after enrollment, and within 1 week before discharge
measure: The maximum body temperature of each day
timeFrame: From enrollment to discharge
measure: Length of stay
timeFrame: After diagnosis
measure: Complications
timeFrame: During hospitalization
Other outcomes:
Locations:
city: Wuhu
country: China
facility: First Affiliated Hospital of Wannan Medical College
state: Anhui
city: Guangzhou
country: China
facility: Zhujiang Hospital of Southern Medical University
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen Second People's Hospital
state: Guangdong
city: Wuxi
country: China
facility: 904 Hospital of the People's Liberation Army Joint Logistic Support Force
state: Jiangsu
city: Shanghai
country: China
facility: Huashan Hospital
state: Shanghai
city: Shanghai
country: China
facility: Renji Hospital, School of Medicine, Shanghai Jiaotong University
state: Shanghai
city: Hangzhou
country: China
facility: First Affiliated Hospital of Zhejiang University
state: Zhejiang
Study officials:
affiliation: Renji Hospital, School of Medicine, Shanghai Jiaotong University
name: Jiyao Jiang, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Renji Hospital, School of Medicine, Shanghai Jiaotong University
name: Junfeng Feng, Dr
role: STUDY_DIRECTOR
affiliation: Southern Medical University, China
name: Qinghua Wang, Dr
role: STUDY_DIRECTOR
affiliation: First Affiliated Hospital of Zhejiang University
name: Xiaofeng Yang, Dr
role: STUDY_DIRECTOR
affiliation: 904th Hospital of the Joint Logistics Support Force of the PLA
name: Likun Yang, Dr
role: STUDY_DIRECTOR
affiliation: Shenzhen Second People's Hospital
name: Xianjian Huang, Dr
role: STUDY_DIRECTOR
affiliation: First Affiliated Hospital of Wannan Medical College
name: Xuefei Shao, Dr
role: STUDY_DIRECTOR
affiliation: Huashan Hospital
name: Jin Hu, Dr
role: STUDY_DIRECTOR
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