Infection
Conditions
Keywords
catheter site infection, catheter colonization, catheter related blood stream infection, patients with central venous catheters
Brief summary
The purpose of this study is to determine whether treatment with topical omiganan is more effective than treatment with topical povidone-iodine in preventing local catheter site infections and catheter colonization in patients who have central venous catheters.
Detailed description
Study design: This is a phase 3, multi-center, randomized, Evaluation Committee-blinded study in patients undergoing noncuffed central venous catheterization using either a single lumen or multi-lumen catheter, and for whom the catheter is expected to be in place for at least 48 hours and for no longer than 28 days. Patients will be randomized within 4 hours of the insertion of the first study CVC. The first study catheter for all patients must be a noncuffed (nontunneled) central venous catheter (CVC). Additionally, only catheters inserted using povidone iodine to prepare the insertion site are eligible to become study catheters. CVCs will be inserted either into the axillary, jugular, subclavian, or femoral vein. Following the first study CVC insertion, additional CVCs, as well as arterial catheters and PICC lines will be allowed as study catheters. Only catheters that have not been impregnated with an antimicrobial substance (e.g. bonded catheters, antimicrobial impregnated, silver tipped, etc) may be used as study catheters. Study catheters must have a skin/catheter interface; for example, introducers will be allowed as study catheters but any catheter, including a CVC, inserted through the introducer will be deemed a non-study catheter. Once a patient has been randomized to either treatment, all study catheters will receive the same treatment. NIH (NCID) and/or local hospital guidelines will be followed for maximal sterile barrier precautions. The catheter site will be disinfected using 10% povidone iodine for a minimum of 2 minutes per established CDC guidelines prior to catheter insertion. Patients randomized to the omiganan 1% gel group will receive an application of omiganan 1% gel around the catheter insertion site following catheter insertion. Patients randomized to the povidone iodine group will receive no further antisepsis treatment other than cleansing the site with povidone iodine at dressing changes. For patients in both groups, the catheterization site will be covered with a semitransparent dressing provided by the sponsor. Every 3 days the dressing will be changed. Skin irritation, erythema and edema will be assessed as well as the presence of purulence, moisture, ecchymosis, abnormally warm tissue temperature and/or site pain/tenderness. Patients will be discharged from the study following the removal of the final study catheter or on study day 28, whichever is sooner. Patients or their legal representatives will be contacted at least 28 days after study discharge/withdrawal for safety follow-up purposes.
Interventions
DRUGOmiganan 1% gel
Patients randomized to omiganan group will receive an application of omiganan gel around the catheter insertion site following catheter insertion. Every 3 days the dressing will be changed and patients will receive a new application of Omiganan 1% gel.
All CVC sites will be disinfected using a 10% povidone-iodine scrub for a minimum of 2 minutes prior to catheter insertion. Patients randomized to the povidone-iodine group will receive no further antiseptic treatment after catheter insertion until dressing changes. Every three days the dressing will be changed and the catheter site will be sterilized with povidone-iodine.
Sponsors
Cadence Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* New insertion of at least 1 noncuffed (nontunneled) temporary central venous catheter * Males and females of at least 13 years of age * A negative urine or serum pregnancy test at baseline
Exclusion criteria
* Insertion of, or requirement for, any study catheter impregnated/bonded with an antimicrobial substance * High probability of death within 14 days of enrollment as assessed by the investigator * Prior treatment with vancomycin (intravenous administration only), daptomycin, linezolid, or quinupristin/dalfopristin, within 48 hours of first study catheter insertion or prior treatment with tigecycline within one week of first study catheter insertion * Requirement for topical antibiotic use within 10 cm of any study catheterization site * Known severe neutropenia (absolute neutrophil count \[ANC\] \< 500 mm3) or recent administration of antineoplastic therapy expected to result in severe neutropenia within 48 hours of first study catheter insertion * Routine non-complicated coronary artery bypass grafting (CABG) patients, bone marrow transplant (BMT) or solid organ transplant (SOT) patients * Patients anticipated to be catheterized for less than 48 hours * Patients who have a suspected or known bloodstream infection at enrollment * Burn patients or patients with toxic epidermal necrolysis * Known allergy to adhesive tape or adhesive bandages
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Local Catheter Site Infection (LCSI) | study completion | LCSI was defined as a study catheter showing any 2 of the following criteria: erythema \>= 2; edema \>= 2; presence of purulence, pain, or abnormal study catheter site warmth. In addition, an action must have been taken that indicated a LCSI was present. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Microbiologically-confirmed LCSI | study completion | MCLCSI is a subset of EC-adjudicated LCSI for any catheter where there is (1) growth of a recognized pathogen from a culture or any purulence or exudate from the same insertion site, or (2) a positive culture of the subcutaneous segment of the catheter meeting criteria for significant colonization. |
| Catheter Colonization (CC) | study completion | CC was defined as a positive culture of any catheter segment \>= 15 CFU (roll-plate method) or \>999 CFU/ml (sonication method) or a positive blood culture drawn via the catheter where the time-to-positivity difference of catheter line vs. peripheral blood \>120 minutes (catheter positive first). |
Countries
France, Germany, Spain, United States
Participant flow
Recruitment details
A total of 1859 hospitalized patients in the US and EU who required new insertion of short-term central venous catheter were enrolled. Study recruitment began in August 2005 and was completed in April 2008.
Pre-assignment details
Patients were randomized within 4 hours of insertion of the first study CVC. There were a total of 44 patients who were randomized but never received insertion of CVC or exposure to assigned treatment, who were excluded from the evaluable population and were not reviewed by the Evaluation Committee.
Participants by arm
| Arm | Count |
|---|---|
| Omiganan 1% Gel | 907 |
| Povidone-Iodine | 908 |
| Total | 1,815 |
Baseline characteristics
| Characteristic | Omiganan 1% Gel | Povidone-Iodine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 7 Participants | 8 Participants |
| Age, Categorical >=65 years | 418 Participants | 402 Participants | 820 Participants |
| Age, Categorical Between 18 and 65 years | 488 Participants | 499 Participants | 987 Participants |
| Age Continuous | 60.1 years STANDARD_DEVIATION 16.82 | 59.4 years STANDARD_DEVIATION 17.17 | 59.7 years STANDARD_DEVIATION 17 |
| Region of Enrollment Europe | 543 participants | 542 participants | 1085 participants |
| Region of Enrollment United States | 364 participants | 366 participants | 730 participants |
| Sex: Female, Male Female | 350 Participants | 362 Participants | 712 Participants |
| Sex: Female, Male Male | 557 Participants | 546 Participants | 1103 Participants |
Outcome results
Primary
Local Catheter Site Infection (LCSI)
LCSI was defined as a study catheter showing any 2 of the following criteria: erythema \>= 2; edema \>= 2; presence of purulence, pain, or abnormal study catheter site warmth. In addition, an action must have been taken that indicated a LCSI was present.
Time frame: study completion
Population: MITT among Survivors: patients from the MITT population (all ITT patients who did not have a baseline BSI) who did not die on study, or who died and were positive (indeterminate or failure) for LCSI prior to death (as determined by EC adjudication).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omiganan 1% Gel | Local Catheter Site Infection (LCSI) | 50 Events |
| Povidone-Iodine | Local Catheter Site Infection (LCSI) | 70 Events |
Comparison: Adequate power was provided to test the null hypothesis that there would be no difference between treatment groups for LCSI. Overall LCSI rate was assumed to be approx. 7.5%, with reduction of LCSI by 40% with omiganan. LCSI rates in placebo and omiganan groups would be 9.375% and 5.625%. Sample size of 1548 in MITT set would provide 80% power to detect this difference between treatments. Sample size was also increased by 19% to account for deaths, for total of 1850 planned patients.p-value: 0.08295% CI: [-0.3, 4.81]Cochran-Mantel-Haenszel
Secondary
Catheter Colonization (CC)
CC was defined as a positive culture of any catheter segment \>= 15 CFU (roll-plate method) or \>999 CFU/ml (sonication method) or a positive blood culture drawn via the catheter where the time-to-positivity difference of catheter line vs. peripheral blood \>120 minutes (catheter positive first).
Time frame: study completion
Population: MITT Among Survivors: patients from the MITT population (all ITT patients who did not have a baseline BSI) who did not die on study, or who died and were positive (indeterminate or failure) for catheter colonization prior to death (as determined EC adjudication).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omiganan 1% Gel | Catheter Colonization (CC) | 369 Events |
| Povidone-Iodine | Catheter Colonization (CC) | 478 Events |
p-value: <0.00195% CI: [6.7, 16.11]Cochran-Mantel-Haenszel
Secondary
Microbiologically-confirmed LCSI
MCLCSI is a subset of EC-adjudicated LCSI for any catheter where there is (1) growth of a recognized pathogen from a culture or any purulence or exudate from the same insertion site, or (2) a positive culture of the subcutaneous segment of the catheter meeting criteria for significant colonization.
Time frame: study completion
Population: MITT among Survivors: patients from the MITT population (all ITT patients who did not have a baseline BSI) who did not die on study, or who died and were positive (indeterminate or failure) for MCLCSI prior to death (as determined by EC adjudication).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omiganan 1% Gel | Microbiologically-confirmed LCSI | 31 Events |
| Povidone-Iodine | Microbiologically-confirmed LCSI | 62 Events |
p-value: 0.00295% CI: [1.4, 5.93]Cochran-Mantel-Haenszel