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Trial registered on ANZCTR


Trial ID
ACTRN12613000757718
Ethics application status
Not yet submitted
Date submitted
16/06/2013
Date registered
8/07/2013
Date last updated
8/07/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
The role of lumbar drainage in the treatment of post-neurosurgical bacterial meningitis
Scientific title
A randomized controlled trial to evaluate the effects of lumbar drainage as an adjunctive treatment to antibiotic therapy in patients with post-neurosurgical nosocomial bacterial meningitis
Secondary ID [1] 282682 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
central nervous system infection 289387 0
nosocomial bacterial meningitis 289388 0
Condition category
Condition code
Infection 289717 289717 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Enrolled subjects will receive antibiotic therapy combined with continuous lumbar drainage. The procedure of lumbar drainage will be performed at bedside or in an operating room, which will take about 30-45 minutes. After that, continuous cerebrospinal fluid drainage will be maintained at a target draining speed of 8-12 mL/h throughout antibiotic treatment which is approximately 7-10 days. Cellular, biochemical, and microbial analysis of cerebrospinal fluid will be performed daily. The choice of antibiotic agents is dependent on the result from bacterial antibiotic resistant tests. Antibiotic agents will mainly be used intravenously, and their dosage and frequency will stick to the recommendations from the manufacturers. As for vancomycin and gentamicin which have weak permeability into cerebrospinal fluid, intrathecal administration of vancomycin 20 mg or gentamicin 8mg will be used once daily through the draining catheter. One-hour clamping of the draining catheter is mandatory after intrathecal administration.
Intervention code [1] 287340 0
Treatment: Surgery
Comparator / control treatment
Subjects will receive antibiotic therapy alone. The choice of antibiotic agents is dependent on the result from bacterial antibiotic resistant tests. Antibiotic agents will mainly be used intravenously, and their dosage and frequency will stick to the recommendations from the manufacturers, which will take approximately 2 weeks. As for vancomycin and gentamicin which have weak permeability into cerebrospinal fluid, intrathecal administration of vancomycin 20 mg or gentamicin 8mg will be used once daily by means of lumbar puncture. Cellular, biochemical, and microbial analysis of cerebrospinal fluid will be performed daily by collecting samples before intrathecal administration of antibiotic agents.
Control group
Active

Outcomes
Primary outcome [1] 289809 0
A cure measured by resolution of meningitis-related clinical manifestations and normalization of cerebrospinal fluid characteristics, or death due to uncontrolled bacterial meningitis
Timepoint [1] 289809 0
Monitored on a daily basis until reaching the primary outcome
Primary outcome [2] 289810 0
Intracranial complications due to meningitis, including hydrocephalus and seizure. Hydrocephalus is diagnosed by clinical manifestations combined with enlarged ventricular size on computerized tomography scans. Seizure is diagnosed by clinical manifestations combined with electroencephalographic evidence.
Timepoint [2] 289810 0
Monitored on a daily basis until 6 months after the meningitis
Secondary outcome [1] 303282 0
Duration of antibiotic usage calculated by days of intravenous antibiotic administration
Timepoint [1] 303282 0
Monitored on a daily basis until discharge
Secondary outcome [2] 303283 0
Days of meningitis-related clinical manifestations, including fever and impaired consciousness measured by the Glasgow Coma Scale score.
Timepoint [2] 303283 0
Monitored on a daily basis until discharge
Secondary outcome [3] 303284 0
Days of normalization of cerebrospinal fluid characteristics, including white cell count, glucose and protein concentration, and microbial culture and Gram's staining .
Timepoint [3] 303284 0
Monitored on a daily basis until discharge

Eligibility
Key inclusion criteria
(1) postoperative or post-traumatic patients with nosocomial bacterial meningitis diagnosed by clinical manifestations in combination with positive results from cerebrospinal fluid culture and/or Gram's staining; (2) No clinical or radiographic signs of impending brain herniation;(3) informed consent is obtained from family members
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
(1) Failure to obtain informed consent; (2) Patients with unremovable infected neurosurgical devices; (3) Presence of coagulation disorders or thrombocytopenia ; (4) Presence of chronic heart failure, respiratory insufficiency, liver dysfunction or renal impairment ; (5) Patients on immunosuppressors;(6) Pregnancy

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Identical preoperative preparations, computer-generated randomization. Envelops containing computer-generated randomized numbers are not opened until operations begin.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated randomized numbers
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Calculations for sample size were based on the outcomes from published works. With an approximate morality rate of 30% in patients with post-neurosurgical nosocomial meningitis, each group of 120 patients would be needed to show a 50% absolute benefit with 80% power (two-sided significance level of 0·05). A safety margin of 25% was built in to allow for protocol violations and crossovers, making a total sample size of 300.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 5145 0
China
State/province [1] 5145 0
Shanghai

Funding & Sponsors
Funding source category [1] 287454 0
Hospital
Name [1] 287454 0
Shanghai Tenth People's Hospital, Tongji University
Address [1] 287454 0
301 Middle Yanchang Road, Shanghai, China, 200072
Country [1] 287454 0
China
Primary sponsor type
Individual
Name
Ke Wang
Address
301 Middle Yanchang Road, Shanghai, China, 200072
Country
China
Secondary sponsor category [1] 286198 0
Individual
Name [1] 286198 0
Meiqing Lou
Address [1] 286198 0
301 Middle Yanchang Road, Shanghai, China, 200072
Country [1] 286198 0
China

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 289540 0
Institutional Ethics Committee of Shanghai Tenth People's Hospital, Tongji University
Ethics committee address [1] 289540 0
301 Middle Yanchang Road, Shanghai, China, 200072
Ethics committee country [1] 289540 0
China
Date submitted for ethics approval [1] 289540 0
01/08/2013
Approval date [1] 289540 0
Ethics approval number [1] 289540 0

Summary
Brief summary
Neurosurgical patients are at a high risk of nosocomial bacterial meningitis (NBM), which results in high morbidity and mortality. Except antibiotic treatment, few therapeutic approaches have been proven to be effective in the treatment of NBM. Therefore, new therapeutic approaches need to be explored. Patients with bacterial meningitis usually present with abnormal characteristics of cerebrospinal fluid (CSF), including elevated white cell count, increased protein concentration, and reduced glucose level. The abnormal CSF constitutes a noxious stimulus to central nervous system and arouses a series of clinical manifestations including fever, nuchal stiffness, and impaired consciousness. Therefore, we suppose that drainage of abnormal CSF may lead to more rapid resolution of clinical manifestations or even a higher probability of a cure. This study aims to evaluate the role of lumbar drainage as an adjunctive treatment to antibiotic therapy in the treatment of post-neurosurgical nosocomial bacterial meningitis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 40818 0
Dr Ke Wang
Address 40818 0
Ke Wang Shanghai Tenth People's Hospital, Tongji University 301 Middle Yanchang Road, Shanghai, China, 200072
Country 40818 0
China
Phone 40818 0
86-02166307370
Fax 40818 0
Email 40818 0
trizzt@gmail.com
Contact person for public queries
Name 40819 0
Dr Ke Wang
Address 40819 0
Ke Wang Shanghai Tenth People's Hospital, Tongji University 301 Middle Yanchang Road, Shanghai, China, 200072
Country 40819 0
China
Phone 40819 0
86-02166307370
Fax 40819 0
Email 40819 0
trizzt@gmail.com
Contact person for scientific queries
Name 40820 0
Dr Ke Wang
Address 40820 0
Ke Wang Shanghai Tenth People's Hospital, Tongji University 301 Middle Yanchang Road, Shanghai, China, 200072
Country 40820 0
China
Phone 40820 0
86-02166307370
Fax 40820 0
Email 40820 0
trizzt@gmail.com