Safety and Efficacy of Ventricular Irrigation for Ventriculitis

Central Nervous System Infections Clinical Trial

Official title:

Safety and Efficacy of Ventricular Irrigation for Ventriculitis: a Randomized Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06358209
• Other study ID #: LY2024-045-B
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 1, 2024
• Est. completion date: May 30, 2026

Study information

• Verified date: April 2024
• Source: RenJi Hospital
• Contact: Jiyao Jiang, Dr
• Phone: 021-68383729
• Email: jiyaojiang[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 104
• Est. completion date: May 30, 2026
• Est. primary completion date: May 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Age 18-65 years old;

• Clinical criteria: 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. Patient has at least two of the following: i. fever (>38.0°C) or headache, ii. meningeal sign(s), iii. cranial nerve sign(s), And at least one of the following: a. increased white cells, elevated protein, and decreased glucose in CSF, b. organism(s) seen on Gram stain of CSF, c. organism(s) identified from blood by a culture or non-culture based microbiologic testing method, d. diagnostic single antibody titer (IgM) or 4-fold increase in paired sera (IgG) for organism;

• Radiological Criteria: Cranial CT or MRI indicating intraventricular floccule or pus

• With consent form

Exclusion Criteria:

• Unstable vital signs

• With surgical indications including brain herniation, acute hydrocephalus

• With comorbidities complicating infection control, including uncontrolled diabetes and hypoproteinemia

• With propensity for bleeding, including history of hemophilia, anticoagulant medication, and abnormal coagulation upon admission

• Pregnancy

Related Conditions & MeSH terms

• Central Nervous System Infections

Intervention

Procedure:
• Ventricular irrigation
Dual-catheter ventricular irrigation, with the lavage catheter placed in the frontal horn of lateral ventricle, and the drainage catheter placed through another burr hole in the ipsilateral occipital horn or in the contralateral ventricle. Lavage is performed twice daily, with each time 500ml of saline over a duration of one hour. Aside from lavage sessions, the lavage is paused, but continuous CSF drainage remains open.

Locations

Country	Name	City	State
China	Zhujiang Hospital of Southern Medical University	Guangzhou	Guangdong
China	First Affiliated Hospital of Zhejiang University	Hangzhou	Zhejiang
China	Huashan Hospital	Shanghai	Shanghai
China	Renji Hospital, School of Medicine, Shanghai Jiaotong University	Shanghai	Shanghai
China	Shenzhen Second People's Hospital	Shenzhen	Guangdong
China	First Affiliated Hospital of Wannan Medical College	Wuhu	Anhui
China	904 Hospital of the People's Liberation Army Joint Logistic Support Force	Wuxi	Jiangsu

Sponsors (7)

Lead Sponsor	Collaborator
RenJi Hospital	904 Hospital of the People's Liberation Army Joint Logistic Support Force, First Affiliated Hospital of Wannan Medical College, First Affiliated Hospital of Zhejiang University, Huashan Hospital, Shenzhen Second People's Hospital, Southern Medical University, China

Country where clinical trial is conducted

China, 

References & Publications (16)

Al Menabbawy A, El Refaee E, Soliman MAR, Elborady MA, Katri MA, Fleck S, Schroeder HWS, Zohdi A. Outcome improvement in cerebral ventriculitis after ventricular irrigation: a prospective controlled study. J Neurosurg Pediatr. 2020 Sep 4;26(6):682-690. doi: 10.3171/2020.5.PEDS2063. — View Citation

Chan AK, Birk HS, Yue JK, Winkler EA, McDermott MW. Bilateral External Ventricular Drain Placement and Intraventricular Irrigation Combined with Concomitant Serial Prone Patient Positioning: A Novel Treatment for Gravity-Dependent Layering in Bacterial Ventriculitis. Cureus. 2017 Apr 18;9(4):e1175. doi: 10.7759/cureus.1175. — View Citation

de Sousa Carvalho Dezena JE, Gerbelli CLB, Braga TKK, Ballestero MFM. How I do it: brainwashing for purulent ventriculitis. Acta Neurochir (Wien). 2023 Nov;165(11):3267-3269. doi: 10.1007/s00701-023-05607-5. Epub 2023 May 20. — View Citation

Gaderer C, Schaumann A, Schulz M, Thomale UW. Neuroendoscopic lavage for the treatment of CSF infection with hydrocephalus in children. Childs Nerv Syst. 2018 Oct;34(10):1893-1903. doi: 10.1007/s00381-018-3894-7. Epub 2018 Jul 11. — View Citation

Hasbun R. Healthcare-associated ventriculitis: current and emerging diagnostic and treatment strategies. Expert Rev Anti Infect Ther. 2021 Aug;19(8):993-999. doi: 10.1080/14787210.2021.1866544. Epub 2020 Dec 24. — View Citation

Humphreys H, Jenks PJ. Surveillance and management of ventriculitis following neurosurgery. J Hosp Infect. 2015 Apr;89(4):281-6. doi: 10.1016/j.jhin.2014.12.019. Epub 2015 Jan 29. — View Citation

Karvouniaris M, Brotis A, Tsiakos K, Palli E, Koulenti D. Current Perspectives on the Diagnosis and Management of Healthcare-Associated Ventriculitis and Meningitis. Infect Drug Resist. 2022 Feb 28;15:697-721. doi: 10.2147/IDR.S326456. eCollection 2022. — View Citation

Karvouniaris M, Brotis AG, Tsiamalou P, Fountas KN. The Role of Intraventricular Antibiotics in the Treatment of Nosocomial Ventriculitis/Meningitis from Gram-Negative Pathogens: A Systematic Review and Meta-Analysis. World Neurosurg. 2018 Dec;120:e637-e650. doi: 10.1016/j.wneu.2018.08.138. Epub 2018 Aug 29. — View Citation

Luque-Paz D, Revest M, Eugene F, Boukthir S, Dejoies L, Tattevin P, Le Reste PJ. Ventriculitis: A Severe Complication of Central Nervous System Infections. Open Forum Infect Dis. 2021 Apr 29;8(6):ofab216. doi: 10.1093/ofid/ofab216. eCollection 2021 Jun. — View Citation

Ochoa A, Arganaraz R, Mantese B. Neuroendoscopic lavage for the treatment of pyogenic ventriculitis in children: personal series and review of the literature. Childs Nerv Syst. 2022 Mar;38(3):597-604. doi: 10.1007/s00381-021-05413-3. Epub 2021 Nov 13. — View Citation

Qin G, Liang Y, Xu K, Xu P, Ye J, Tang X, Lan S. Neuroendoscopic lavage for ventriculitis: Case report and literature review. Neurochirurgie. 2020 Apr;66(2):127-132. doi: 10.1016/j.neuchi.2019.12.005. Epub 2020 Feb 19. — View Citation

Rogers T, Sok K, Erickson T, Aguilera E, Wootton SH, Murray KO, Hasbun R. Impact of Antibiotic Therapy in the Microbiological Yield of Healthcare-Associated Ventriculitis and Meningitis. Open Forum Infect Dis. 2019 Feb 6;6(3):ofz050. doi: 10.1093/ofid/ofz050. eCollection 2019 Mar. — View Citation

Stati G, Migliorino E, Moneti M, Castioni CA, Scibilia A, Palandri G, Virgili G, Aspide R. Treatment of cerebral ventriculitis with a new self-irrigating catheter system: narrative review and case series. J Anesth Analg Crit Care. 2023 Nov 8;3(1):46. doi: 10.1186/s44158-023-00131-5. — View Citation

Terada Y, Mineharu Y, Arakawa Y, Funaki T, Tanji M, Miyamoto S. Effectiveness of neuroendoscopic ventricular irrigation for ventriculitis. Clin Neurol Neurosurg. 2016 Jul;146:147-51. doi: 10.1016/j.clineuro.2016.05.010. Epub 2016 May 9. — View Citation

Tomita Y, Shimazu Y, Kawakami M, Matsumoto H, Fujii K, Kameda M, Yasuhara T, Suruga Y, Ota T, Kimata Y, Kurozumi K, Date I. Pyogenic Ventriculitis After Anterior Skull Base Surgery Treated With Endoscopic Ventricular Irrigation And Reconstruction Using a Vascularized Flap. Acta Med Okayama. 2021 Apr;75(2):243-248. doi: 10.18926/AMO/61908. — View Citation

Tunkel AR, Hasbun R, Bhimraj A, Byers K, Kaplan SL, Scheld WM, van de Beek D, Bleck TP, Garton HJL, Zunt JR. 2017 Infectious Diseases Society of America's Clinical Practice Guidelines for Healthcare-Associated Ventriculitis and Meningitis. Clin Infect Dis. 2017 Mar 15;64(6):e34-e65. doi: 10.1093/cid/ciw861. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Complications	Number of participants with complications within 6 months after diagnosis of ventriculitis	Within 6 months after diagnosis
Primary	Mortality rate	All-cause mortality rate at 6 months after diagnosis of ventriculitis	6 months after diagnosis
Secondary	GOSE	Extended Glasgow Outcome Scale within 6 months after diagnosis of ventriculitis	Within 6 months after diagnosis
Secondary	CRS-R	Coma Recovery Scale - Revised within 6 months after diagnosis of ventriculitis	Within 6 months after diagnosis
Secondary	DRS	Disability Rating Scale within 6 months after diagnosis of ventriculitis	Within 6 months after diagnosis
Secondary	mRS	Modified Rankin Scale within 6 months after diagnosis of ventriculitis	Within 6 months after diagnosis
Secondary	Microbial culture	Results of CSF culture within 6 months after diagnosis of ventriculitis	Within 6 months after diagnosis
Secondary	CSF glucose	CSF glucose level within 6 months after diagnosis of ventriculitis	Within 6 months after diagnosis
Secondary	CSF protein	CSF protein level within 6 months after diagnosis of ventriculitis	Within 6 months after diagnosis
Secondary	CSF WBC count	CSF white blood cell count within 6 months after diagnosis of ventriculitis	Within 6 months after diagnosis
Secondary	Length of stay	Length of hospital stay	Within 6 months after diagnosis