Comparative Infection Rates for the Codman BACTISEAL TM External Ventricular Drainage (EVD) System

Study Overview
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Brief Summary
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The purpose of this non-significant risk study is to establish initial baseline infection rates for the Codman BACTISEAL External Ventricular Drainage (B-EVD) System (Antibiotic impregnated catheter) and to compare relative rates of ventriculostomy-related infection between Subjects with BACTISEAL or conventional EVD catheters in a prospective, randomized open label study

Detailed Description
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External ventricular drainage catheters are widely used in the management of Subjects with elevated intra-cranial pressure (ICP) secondary to acute hydrocephalus due to sub-arachnoid hemorrhage, intra-cerebral hemorrhage, intra-ventricular hemorrhage and other causes that obstruct the cerebrospinal fluid (CSF) circulation. However, this mode of treatment could be compromised by the increased risk of catheter related CSF infection. B-EVD is manufactured using a patented process to impregnate silicone catheters with two antibiotics, rifampin and clindamycin. These antibiotics are impregnated throughout the silicone matrix. After implantation, slow release of both antibiotics at the extra- and intra-luminal catheter surfaces minimizes the likelihood of bacterial colonization. The B-EVD Catheter System has, to date, been well accepted by domestic and European customers. Currently there exists sound scientific rationale and promising bench-top in vitro data to anticipate low levels of ventriculostomy-related infection in Subjects using this system. Published BACTISEAL shunt data and direct feedback from U.S. market experience also support this notion. There are no published clinical studies reporting infection rates with the use of the B-EVD System, making all statements regarding its propensity to minimize clinical risk for catheter-related infection mere speculation and anecdotal. Therefore, Codman proposes to undertake a controlled clinical evaluation of this product to demonstrate its influence on EVD catheter-related infections, using a conventional EVD catheter as a standard of reference. Immediately following successful screening, the Subject will be randomized to test or control group and will have the appropriate EVD system implanted. The Treatment Phase will cover the duration of the implanted EVD system. Subjects will be monitored for 2 weeks post-explant. This study is expected to enroll 600 evaluable implanted Subjects at up to 15 Investigational Sites in US, Europe and Asia-Pacific

Official Title
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Establishment of Baseline and Comparative Infection Rates for the Codman BACTISEAL TM External Ventricular Drainage (EVD) System

Conditions
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Intraventricular Hemorrhage, Subarachnoid Hemorrhage

Intervention / Treatment
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* Device: Bactiseal TM EVD
* Device: Standard EVD Catheter


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The Subject is 18 years or older. The Subject (family member/legal representative) has given written Informed Consent prior to enrollment into this trial OR, where the Subject is unable to consent and no relative/legal representative is available to offer consent, appropriate legal and ethical practices are employed and thoroughly documented according to the laws and policies of the respective country and institution. The Subject (family member/legal representative) is willing to participate in this trial for the duration of the implanted EVD system and is willing to comply with the protocol requirements. Exclusion Criteria: Within the preceding 30 days, the Subject has enrolled or participated in another trial utilizing an anti-microbial drug or medical device implanted in or directly influencing the CNS and/or spinal cord. The Subject is pregnant or lactating. The Subject has a suspected or documented allergy to the materials of the EVD system, including silicone, rifampin and clindamycin. The Subject has a positive CSF culture prior to EVD implant. The Subject is immunocompromised. The Subject requires more than one ventricular catheter concurrently. The Subject has had an EVD catheter within the previous 30 days. The Subject has sepsis, ventriculitis, meningitis, a skin infection/inflammation at or near the implantation site, an ear infection on either side, or a severe respiratory tract infection that, in the opinion of the Investigator, would most likely compromise the effectiveness of the EVD system. The Subject is known to have received systemic antibiotic therapy within a 14-day period preceding screening for inclusion in this trial. The Subject has an uncontrolled coagulopathy or any other known bleeding diathesis. The Subject is otherwise determined by the Investigator to be medically unsuitable for participation in this trial. The Subject is a prisoner.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bactiseal TM EVD<br>Bactiseal External Ventricular Drainage System. | Device: Bactiseal TM EVD<br>* Standard of care implantation of external ventricular drainage catheter<br>* Other names: EVD,Bactiseal, standard;|
| Active Comparator: Standard EVD Catheter<br>Standard External Ventricular Device system | Device: Standard EVD Catheter<br>* Standard of care EVD system other than Bactiseal.<br>* Other names: EVD, ventricular catheters;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Infections | The number of infections for the Codman Bactiseal EVD Catheter and the number of infections for a Standard EVD Catheter (ventriculostomy-related infections). | Duration of implanted EVD system to 2 week post implant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days to Proven Infection | Number of days to proven infection. | Implantation of EVD System to explant of EVD catheter, an average of ten days | 
| Class of Bacterial Agent Causing Proven Infection | Type of bacterial agent related to proven infection in Bactiseal EVD and Standard EVD | Implantation of subject to post implant | 
| Intraluminal Colonization on Catheters | Number of catheters with Bacterial colonization verified using fluorescence. | Implant of subjects to post implant | 
| Device Related Adverse Events | Number of Device Related Adverse Events | Implanted subjects to time of explant | 
| Number of Days With Indwelling Catheter | Days catheter was implanted in subjects | Implant of subjects to day of explant | 
| Average Subject Age | The average subject age | Implant to subject | 
| Diagnosis Requiring EVD Implantation | Primary diagnosis for implantation of EVD system | Implantation of EVD system | 
| Non-infectious Catheter Failure in the MITT Population | Reasons for non-infectious catheter malfunctions in the Modified intent to treat population. | Implant of subject to explant | 
| Time Point of Introduction of Systemic Antibiotic Therapy | Time points of then patients received systemic antibiotic therapy | Within 48 hours of implant of subjects to explant | 
| Hospital Locations for EVD Catheter Placement | Number of subjects in each analysis population where the EVD catheter placement occurred; either in the Intensive Care Unit (ICU)or the Operating Room (OR). | Implantation of subject | 
| Length of Catheter Tunneling Into the Brain | Length of tunneling of EVD catheter in the brain for each analysis population. | Implant of subject | 
| Number of Catheter Insertion Attempts | Number of insertions needed to place catheter | Implantation of subject | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ventriculostomy, EVD