Intraventricular Hemorrhage, Subarachnoid Hemorrhage
Conditions
Keywords
Ventriculostomy, EVD
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
Interventions
DEVICEBactiseal TM EVD
Standard of care implantation of external ventricular drainage catheter
DEVICEStandard EVD Catheter
Standard of care EVD system other than Bactiseal.
Sponsors
Codman & Shurtleff
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Infections | Duration of implanted EVD system to 2 week post implant | The number of infections for the Codman Bactiseal EVD Catheter and the number of infections for a Standard EVD Catheter (ventriculostomy-related infections). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Class of Bacterial Agent Causing Proven Infection | Implantation of subject to post implant | Type of bacterial agent related to proven infection in Bactiseal EVD and Standard EVD |
| Intraluminal Colonization on Catheters | Implant of subjects to post implant | Number of catheters with Bacterial colonization verified using fluorescence. |
| Device Related Adverse Events | Implanted subjects to time of explant | Number of Device Related Adverse Events |
| Number of Days With Indwelling Catheter | Implant of subjects to day of explant | Days catheter was implanted in subjects |
| Average Subject Age | Implant to subject | The average subject age |
| Days to Proven Infection | Implantation of EVD System to explant of EVD catheter, an average of ten days | Number of days to proven infection. |
| Non-infectious Catheter Failure in the MITT Population | Implant of subject to explant | Reasons for non-infectious catheter malfunctions in the Modified intent to treat population. |
| Time Point of Introduction of Systemic Antibiotic Therapy | Within 48 hours of implant of subjects to explant | Time points of then patients received systemic antibiotic therapy |
| Hospital Locations for EVD Catheter Placement | Implantation of subject | 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). |
| Length of Catheter Tunneling Into the Brain | Implant of subject | Length of tunneling of EVD catheter in the brain for each analysis population. |
| Number of Catheter Insertion Attempts | Implantation of subject | Number of insertions needed to place catheter |
| Diagnosis Requiring EVD Implantation | Implantation of EVD system | Primary diagnosis for implantation of EVD system |
Countries
Canada, China, France, Hong Kong, Norway, Singapore, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bactiseal EVD | 214 |
| Standard EVD | 220 |
| Total | 434 |
Baseline characteristics
| Characteristic | Bactiseal EVD | Standard EVD | Total |
|---|---|---|---|
| Age Continuous | 51.7 years STANDARD_DEVIATION 16.2 | 54.4 years STANDARD_DEVIATION 14.7 | 53.05 years STANDARD_DEVIATION 15.45 |
| Region of Enrollment Canada | 21 participants | 17 participants | 38 participants |
| Region of Enrollment China | 18 participants | 17 participants | 35 participants |
| Region of Enrollment France | 30 participants | 29 participants | 59 participants |
| Region of Enrollment Hong Kong | 27 participants | 33 participants | 60 participants |
| Region of Enrollment Norway | 30 participants | 26 participants | 56 participants |
| Region of Enrollment Singapore | 14 participants | 11 participants | 25 participants |
| Region of Enrollment United Kingdom | 38 participants | 45 participants | 83 participants |
| Region of Enrollment United States | 36 participants | 42 participants | 78 participants |
| Sex: Female, Male Female | 110 Participants | 110 Participants | 220 Participants |
| Sex: Female, Male Male | 104 Participants | 110 Participants | 214 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 220 | 19 / 214 |
| serious Total, serious adverse events | 16 / 220 | 14 / 214 |
Outcome results
Primary
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).
Time frame: Duration of implanted EVD system to 2 week post implant
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bactiseal EVD Catheter | Number of Infections | Modified intent to Treat | 4 Infections |
| Bactiseal EVD Catheter | Number of Infections | Evaluable | 4 Infections |
| Bactiseal EVD Catheter | Number of Infections | Per Protocol | 1 Infections |
| Standard EVD Cathter | Number of Infections | Modified intent to Treat | 5 Infections |
| Standard EVD Cathter | Number of Infections | Evaluable | 5 Infections |
| Standard EVD Cathter | Number of Infections | Per Protocol | 3 Infections |
Secondary
Average Subject Age
The average subject age
Time frame: Implant to subject
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bactiseal EVD Catheter | Average Subject Age | Modified Intent to Treat | 51.9 Years | Standard Deviation 16.1 |
| Bactiseal EVD Catheter | Average Subject Age | Evaluable | 51.9 Years | Standard Deviation 16.1 |
| Bactiseal EVD Catheter | Average Subject Age | Per protocol | 49.4 Years | Standard Deviation 15.8 |
| Standard EVD Cathter | Average Subject Age | Modified Intent to Treat | 54.4 Years | Standard Deviation 14.7 |
| Standard EVD Cathter | Average Subject Age | Evaluable | 54.5 Years | Standard Deviation 14.6 |
| Standard EVD Cathter | Average Subject Age | Per protocol | 54.2 Years | Standard Deviation 14.2 |
Secondary
Class of Bacterial Agent Causing Proven Infection
Type of bacterial agent related to proven infection in Bactiseal EVD and Standard EVD
Time frame: Implantation of subject to post implant
Population: All subjects included in the MITT, Evaluable and Per-Protocol population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bactiseal EVD Catheter | Class of Bacterial Agent Causing Proven Infection | Bacilli | 11 participants |
| Bactiseal EVD Catheter | Class of Bacterial Agent Causing Proven Infection | Gamma Proteobacteria | 0 participants |
| Standard EVD Cathter | Class of Bacterial Agent Causing Proven Infection | Bacilli | 0 participants |
| Standard EVD Cathter | Class of Bacterial Agent Causing Proven Infection | Gamma Proteobacteria | 6 participants |
Secondary
Days to Proven Infection
Number of days to proven infection.
Time frame: Implantation of EVD System to explant of EVD catheter, an average of ten days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bactiseal EVD Catheter | Days to Proven Infection | Modified Intent to Treat | 9.5 Days | Standard Deviation 3.3 |
| Bactiseal EVD Catheter | Days to Proven Infection | Evaluable | 9.5 Days | Standard Deviation 3.3 |
| Bactiseal EVD Catheter | Days to Proven Infection | Per protocol | 14 Days | Standard Deviation 1 |
| Standard EVD Cathter | Days to Proven Infection | Modified Intent to Treat | 10 Days | Standard Deviation 3 |
| Standard EVD Cathter | Days to Proven Infection | Evaluable | 10 Days | Standard Deviation 3 |
| Standard EVD Cathter | Days to Proven Infection | Per protocol | 10 Days | Standard Deviation 2.5 |
Secondary
Device Related Adverse Events
Number of Device Related Adverse Events
Time frame: Implanted subjects to time of explant
Population: There were 8 device-related events, 7 of which were in subjects that received a standard catheter. None of the 8 subjects were proven infections.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bactiseal EVD Catheter | Device Related Adverse Events | Modifeid Intent to Treat | 0 events |
| Bactiseal EVD Catheter | Device Related Adverse Events | Evaluable | 1 events |
| Bactiseal EVD Catheter | Device Related Adverse Events | Per protocol | 0 events |
| Bactiseal EVD Catheter | Device Related Adverse Events | Safety | 0 events |
| Standard EVD Cathter | Device Related Adverse Events | Safety | 2 events |
| Standard EVD Cathter | Device Related Adverse Events | Modifeid Intent to Treat | 1 events |
| Standard EVD Cathter | Device Related Adverse Events | Per protocol | 0 events |
| Standard EVD Cathter | Device Related Adverse Events | Evaluable | 4 events |
Secondary
Diagnosis Requiring EVD Implantation
Primary diagnosis for implantation of EVD system
Time frame: Implantation of EVD system
Population: Analysis consisted of combining both Arm/Group (Bactiseal and Standard)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bactiseal EVD Catheter | Diagnosis Requiring EVD Implantation | Edema - Modified Intent to Treat | 20 Participants |
| Bactiseal EVD Catheter | Diagnosis Requiring EVD Implantation | Edema - Evaluable | 17 Participants |
| Bactiseal EVD Catheter | Diagnosis Requiring EVD Implantation | Edema - Per Protocol | 13 Participants |
| Bactiseal EVD Catheter | Diagnosis Requiring EVD Implantation | Hemorrhage - Modified Intent to Treat | 335 Participants |
| Bactiseal EVD Catheter | Diagnosis Requiring EVD Implantation | Hemorrhage - Evaluable | 282 Participants |
| Bactiseal EVD Catheter | Diagnosis Requiring EVD Implantation | Hemorrhage - Per protocol | 197 Participants |
| Bactiseal EVD Catheter | Diagnosis Requiring EVD Implantation | Hydrocephalus - Modified Intent to Treat | 64 Participants |
| Bactiseal EVD Catheter | Diagnosis Requiring EVD Implantation | Hydrocephalus - Evaluable | 58 Participants |
| Bactiseal EVD Catheter | Diagnosis Requiring EVD Implantation | Hydrocephalus - Per Protocol | 50 Participants |
Secondary
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).
Time frame: Implantation of subject
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bactiseal EVD Catheter | Hospital Locations for EVD Catheter Placement | ICU (Evaluable) | 37 Participants |
| Bactiseal EVD Catheter | Hospital Locations for EVD Catheter Placement | ICU (Per Protocol) | 22 Participants |
| Bactiseal EVD Catheter | Hospital Locations for EVD Catheter Placement | OR (MITT) | 159 Participants |
| Bactiseal EVD Catheter | Hospital Locations for EVD Catheter Placement | OR (Per Protocol) | 103 Participants |
| Bactiseal EVD Catheter | Hospital Locations for EVD Catheter Placement | OR (Evaluable) | 136 Participants |
| Bactiseal EVD Catheter | Hospital Locations for EVD Catheter Placement | ICU (MITT) | 45 Participants |
| Standard EVD Cathter | Hospital Locations for EVD Catheter Placement | OR (Evaluable) | 132 Participants |
| Standard EVD Cathter | Hospital Locations for EVD Catheter Placement | ICU (MITT) | 49 Participants |
| Standard EVD Cathter | Hospital Locations for EVD Catheter Placement | ICU (Evaluable) | 41 Participants |
| Standard EVD Cathter | Hospital Locations for EVD Catheter Placement | OR (MITT) | 153 Participants |
| Standard EVD Cathter | Hospital Locations for EVD Catheter Placement | ICU (Per Protocol) | 25 Participants |
| Standard EVD Cathter | Hospital Locations for EVD Catheter Placement | OR (Per Protocol) | 106 Participants |
Secondary
Intraluminal Colonization on Catheters
Number of catheters with Bacterial colonization verified using fluorescence.
Time frame: Implant of subjects to post implant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bactiseal EVD Catheter | Intraluminal Colonization on Catheters | 0 catheters |
| Standard EVD Cathter | Intraluminal Colonization on Catheters | 3 catheters |
Secondary
Length of Catheter Tunneling Into the Brain
Length of tunneling of EVD catheter in the brain for each analysis population.
Time frame: Implant of subject
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bactiseal EVD Catheter | Length of Catheter Tunneling Into the Brain | MITT | 6.2 cm | Standard Deviation 2.2 |
| Bactiseal EVD Catheter | Length of Catheter Tunneling Into the Brain | Evaluable | 6.2 cm | Standard Deviation 2.1 |
| Bactiseal EVD Catheter | Length of Catheter Tunneling Into the Brain | Per Protocol | 6.0 cm | Standard Deviation 1.9 |
| Standard EVD Cathter | Length of Catheter Tunneling Into the Brain | MITT | 5.8 cm | Standard Deviation 2.1 |
| Standard EVD Cathter | Length of Catheter Tunneling Into the Brain | Evaluable | 5.8 cm | Standard Deviation 2.1 |
| Standard EVD Cathter | Length of Catheter Tunneling Into the Brain | Per Protocol | 5.7 cm | Standard Deviation 1.8 |
Secondary
Non-infectious Catheter Failure in the MITT Population
Reasons for non-infectious catheter malfunctions in the Modified intent to treat population.
Time frame: Implant of subject to explant
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bactiseal EVD Catheter | Non-infectious Catheter Failure in the MITT Population | Occlusion | 16 Participants |
| Bactiseal EVD Catheter | Non-infectious Catheter Failure in the MITT Population | Migration | 0 Participants |
| Bactiseal EVD Catheter | Non-infectious Catheter Failure in the MITT Population | Misplacement | 0 Participants |
| Bactiseal EVD Catheter | Non-infectious Catheter Failure in the MITT Population | Other | 0 Participants |
| Standard EVD Cathter | Non-infectious Catheter Failure in the MITT Population | Other | 3 Participants |
| Standard EVD Cathter | Non-infectious Catheter Failure in the MITT Population | Occlusion | 0 Participants |
| Standard EVD Cathter | Non-infectious Catheter Failure in the MITT Population | Misplacement | 1 Participants |
| Standard EVD Cathter | Non-infectious Catheter Failure in the MITT Population | Migration | 1 Participants |
Secondary
Number of Catheter Insertion Attempts
Number of insertions needed to place catheter
Time frame: Implantation of subject
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bactiseal EVD Catheter | Number of Catheter Insertion Attempts | 3 instertions | 9 insertions |
| Bactiseal EVD Catheter | Number of Catheter Insertion Attempts | 4 instertions | 3 insertions |
| Bactiseal EVD Catheter | Number of Catheter Insertion Attempts | 2 insertions | 15 insertions |
| Bactiseal EVD Catheter | Number of Catheter Insertion Attempts | 5 insertions | 2 insertions |
| Bactiseal EVD Catheter | Number of Catheter Insertion Attempts | 1 Insertion | 177 insertions |
| Standard EVD Cathter | Number of Catheter Insertion Attempts | 5 insertions | 1 insertions |
| Standard EVD Cathter | Number of Catheter Insertion Attempts | 1 Insertion | 178 insertions |
| Standard EVD Cathter | Number of Catheter Insertion Attempts | 2 insertions | 16 insertions |
| Standard EVD Cathter | Number of Catheter Insertion Attempts | 4 instertions | 2 insertions |
| Standard EVD Cathter | Number of Catheter Insertion Attempts | 3 instertions | 11 insertions |
Secondary
Number of Days With Indwelling Catheter
Days catheter was implanted in subjects
Time frame: Implant of subjects to day of explant
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bactiseal EVD Catheter | Number of Days With Indwelling Catheter | Modified Intent to Treat | 8.7 Days | Standard Deviation 5.7 |
| Bactiseal EVD Catheter | Number of Days With Indwelling Catheter | Evaluable | 9.3 Days | Standard Deviation 5.5 |
| Bactiseal EVD Catheter | Number of Days With Indwelling Catheter | Per Protocol | 9.8 Days | Standard Deviation 5.7 |
| Standard EVD Cathter | Number of Days With Indwelling Catheter | Modified Intent to Treat | 8.9 Days | Standard Deviation 6 |
| Standard EVD Cathter | Number of Days With Indwelling Catheter | Evaluable | 9.7 Days | Standard Deviation 5.8 |
| Standard EVD Cathter | Number of Days With Indwelling Catheter | Per Protocol | 10.4 Days | Standard Deviation 5.9 |
Secondary
Time Point of Introduction of Systemic Antibiotic Therapy
Time points of then patients received systemic antibiotic therapy
Time frame: Within 48 hours of implant of subjects to explant
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bactiseal EVD Catheter | Time Point of Introduction of Systemic Antibiotic Therapy | Before implant, but within 48 hours (MITT) | 146 Paticipants |
| Bactiseal EVD Catheter | Time Point of Introduction of Systemic Antibiotic Therapy | Catheter Implanted (MITT) | 167 Paticipants |
| Bactiseal EVD Catheter | Time Point of Introduction of Systemic Antibiotic Therapy | Before implant, but within 48 hours (Evaluable) | 118 Paticipants |
| Bactiseal EVD Catheter | Time Point of Introduction of Systemic Antibiotic Therapy | Catheter Implanted (Evaluable) | 150 Paticipants |
| Bactiseal EVD Catheter | Time Point of Introduction of Systemic Antibiotic Therapy | Before implant, but within 48 hours (Per protocol) | 81 Paticipants |
| Bactiseal EVD Catheter | Time Point of Introduction of Systemic Antibiotic Therapy | Catheter implanted (Per Protocol) | 108 Paticipants |
| Standard EVD Cathter | Time Point of Introduction of Systemic Antibiotic Therapy | Before implant, but within 48 hours (Per protocol) | 90 Paticipants |
| Standard EVD Cathter | Time Point of Introduction of Systemic Antibiotic Therapy | Before implant, but within 48 hours (MITT) | 149 Paticipants |
| Standard EVD Cathter | Time Point of Introduction of Systemic Antibiotic Therapy | Catheter Implanted (Evaluable) | 159 Paticipants |
| Standard EVD Cathter | Time Point of Introduction of Systemic Antibiotic Therapy | Catheter Implanted (MITT) | 175 Paticipants |
| Standard EVD Cathter | Time Point of Introduction of Systemic Antibiotic Therapy | Catheter implanted (Per Protocol) | 121 Paticipants |
| Standard EVD Cathter | Time Point of Introduction of Systemic Antibiotic Therapy | Before implant, but within 48 hours (Evaluable) | 124 Paticipants |