Clinical trial NCT00197392: Comparative Infection Rates for the Codman BACTISEAL TM External Ventricular Drainage (EVD) System
Official title: Establishment of Baseline and Comparative Infection Rates for the Codman BACTISEAL TM External Ventricular Drainage (EVD) System
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Intraventricular Hemorrhage
Subarachnoid Hemorrhage
Keywords: Ventriculostomy
EVD
Lead sponsor: Codman & Shurtleff
Sponsor class: INDUSTRY
First posted: 2005-09-20
Enrollment: 434
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Infections
timeFrame: Duration of implanted EVD system to 2 week post implant
Secondary outcomes:
measure: Days to Proven Infection
timeFrame: Implantation of EVD System to explant of EVD catheter, an average of ten days
measure: Class of Bacterial Agent Causing Proven Infection
timeFrame: Implantation of subject to post implant
measure: Intraluminal Colonization on Catheters
timeFrame: Implant of subjects to post implant
measure: Device Related Adverse Events
timeFrame: Implanted subjects to time of explant
measure: Number of Days With Indwelling Catheter
timeFrame: Implant of subjects to day of explant
measure: Average Subject Age
timeFrame: Implant to subject
measure: Diagnosis Requiring EVD Implantation
timeFrame: Implantation of EVD system
measure: Non-infectious Catheter Failure in the MITT Population
timeFrame: Implant of subject to explant
measure: Time Point of Introduction of Systemic Antibiotic Therapy
timeFrame: Within 48 hours of implant of subjects to explant
measure: Hospital Locations for EVD Catheter Placement
timeFrame: Implantation of subject
measure: Length of Catheter Tunneling Into the Brain
timeFrame: Implant of subject
measure: Number of Catheter Insertion Attempts
timeFrame: Implantation of subject
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: Gainesville
country: United States
state: Florida
city: Syracuse
country: United States
state: New York
city: Hershey
country: United States
state: Pennsylvania
city: Calgary
country: Canada
state: Alberta
city: Edmonton
country: Canada
state: Alberta
city: Sherbrooke
country: Canada
state: Quebec
city: Beijing
country: China
facility: Tiantan Hospital
city: Beijing
country: China
facility: Xuan Wu Hospital
city: Angers
country: France
city: Lille
country: France
city: Paris
country: France
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Oslo
country: Norway
city: Singapore
country: Singapore
facility: National Neuroscience Institute
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Bristol
country: United Kingdom
city: Leeds
country: United Kingdom
city: Salford
country: United Kingdom
Study officials:
affiliation: Unaffilliated
name: J. Thomas Megerian, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Codman in house testing reports, TR2213 and PVER99-133 Addendum
citation: Bayston R. Hydrocephalus Shunt Infections. Chapman and Hall Medical, London, 1989, p. 23.
citation: Bayston R, Grove N, Siegel J, Lawellin D, Barsham S. Prevention of hydrocephalus shunt catheter colonisation in vitro by impregnation with antimicrobials. J Neurol Neurosurg Psychiatry. 1989 May;52(5):605-9. doi: 10.1136/jnnp.52.5.605.
citation: Bayston R, Lambert E. Duration of protective activity of cerebrospinal fluid shunt catheters impregnated with antimicrobial agents to prevent bacterial catheter-related infection. J Neurosurg. 1997 Aug;87(2):247-51. doi: 10.3171/jns.1997.87.2.0247.
citation: Govender ST, Nathoo N, van Dellen JR. Evaluation of an antibiotic-impregnated shunt system for the treatment of hydrocephalus. J Neurosurg. 2003 Nov;99(5):831-9. doi: 10.3171/jns.2003.99.5.0831.
citation: Lozier AP, Sciacca RR, Romagnoli MF, Connolly ES Jr. Ventriculostomy-related infections: a critical review of the literature. Neurosurgery. 2002 Jul;51(1):170-81; discussion 181-2. doi: 10.1097/00006123-200207000-00024.
citation: Schierholz J, Jansen B, Jaenicke L, Pulverer G. In-vitro efficacy of an antibiotic releasing silicone ventricle catheter to prevent shunt infection. Biomaterials. 1994 Oct;15(12):996-1000. doi: 10.1016/0142-9612(94)90080-9.
citation: Zabramski JM, Whiting D, Darouiche RO, Horner TG, Olson J, Robertson C, Hamilton AJ. Efficacy of antimicrobial-impregnated external ventricular drain catheters: a prospective, randomized, controlled trial. J Neurosurg. 2003 Apr;98(4):725-30. doi: 10.3171/jns.2003.98.4.0725.