Study of Omiganan 1% Gel in Preventing Catheter Infections/Colonization in Patients With Central Venous Catheters

• Sponsor: Cadence Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00231153
• Collaborator: (none)
• Enrollment: 1,859
• Locations: 57
• Arms: 2
• Duration (Months): 35
• Patients Per Site: 32.6
• Patients Per Site Per Month: 0.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Infection	Drug: Omiganan 1% gel; Drug: Povidone-Iodine 10%	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1859 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase 3, Multicenter, Randomized, Evaluation Committee-Blinded Study to Assess the Efficacy of Topical Omiganan 1% Gel in Preventing Local Catheter Site Infections/Colonization in Patients Undergoing Central Venous Catheterization
• Study Start Date: Aug 1, 2005
• Actual Primary Completion Date: Jun 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Povidone-Iodine 10%	Drug: Povidone-Iodine 10%; 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.
Experimental: omiganan 1% gel	Drug: Omiganan 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.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 13 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Mobile	Alabama	United States
2		Phoenix	Arizona	United States
3		Arcadia	California	United States
4		Glendale	California	United States
5		Long Beach	California	United States
6		Los Angeles	California	United States
7		Madera	California	United States
8		San Diego	California	United States
9		San Francisco	California	United States
10		Torrance	California	United States
11		Denver	Colorado	United States
12		Bridgeport	Connecticut	United States
13		Jacksonville	Florida	United States
14		Miami	Florida	United States
15		Fort Gordon	Georgia	United States
16		Marietta	Georgia	United States
17		Elk Grove Village	Illinois	United States
18		Hoffman Estates	Illinois	United States
19		Louisville	Kentucky	United States
20		Opelousas	Louisiana	United States
21		Shreveport	Louisiana	United States
22		St. Paul	Minnesota	United States
23		Kansas City	Missouri	United States
24		Camden	New Jersey	United States
25		Newark	New Jersey	United States
26		Brooklyn	New York	United States
27		Jamaica	New York	United States
28		Syracuse	New York	United States
29		Oklahoma City	Oklahoma	United States
30		Pittsburgh	Pennsylvania	United States
31		Memphis	Tennessee	United States
32		El Paso	Texas	United States
33		Fort Worth	Texas	United States
34		Houston	Texas	United States
35		Lubbock	Texas	United States
36		Morgantown	Virginia	United States
37		Bourg en Bresse		France
38		Brive la Gaillarde		France
39		La Roche sur Yon		France
40		Limoges		France
41		Montauban		France
42		Orleans		France
43		Pau		France
44		Poitiers		France
45		Tours		France
46		Halle		Germany
47		Jena		Germany
48		Leipzig		Germany
49		Regensburg		Germany
50		Alcalá de Henares		Spain
51		Barcelona		Spain
52		Cadiz		Spain
53		El Palmar (Murcia)		Spain
54		Las Palmas de Gran Canaria		Spain
55		Madrid		Spain
56		Palma de Mallorca		Spain
57		Sevilla		Spain

Sponsors and Collaborators

• Cadence Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00231153
• Other Study ID Numbers: CPI-226-03; EudraCT Number: 2005-003194-24
• First Posted: Oct 4, 2005
• Last Update Posted: Aug 13, 2009
• Last Verified: Jun 1, 2009

• Keywords provided by , ,: catheter site infection; catheter colonization; catheter related blood stream infection; patients with central venous catheters
• Additional relevant MeSH terms: Infections; Communicable Diseases; Povidone-Iodine; Povidone

Study Results

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 Detail	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.

Arm/Group Title	Omiganan 1% Gel	Povidone-Iodine
Arm/Group Description	All treated patients: Properly consented patients who received 1 or more doses of omiganan 1% gel with any post baseline observations (Primary Safety Population). Modified Intent to Treat Subset: all ITT patients who did not have a BSI at randomization (baseline BSI) as determined by EC adjudication. Patients classified as 'present' (i.e. failure) or 'indeterminate' for baseline BSI were excluded from the MITT population. Patients missing baseline BSI status from EC adjudication were excluded from the MITT population. MITT Among Survivors: patients from the MITT population who did not die on study or who died and were positive (indeterminate or failure)for the study endpoint being analyzed prior to death (as determined by EC adjudication).	All treated patients: Properly consented patients who received 1 or more doses of Povidone-Iodine with any post baseline observations (Primary Safety Population). Modified Intent to Treat Subset: all ITT patients who did not have a BSI at randomization (baseline BSI) as determined by EC adjudication. Patients classified as 'present' (i.e. failure) or 'indeterminate' for baseline BSI were excluded from the MITT population. Patients missing baseline BSI status from EC adjudication were excluded from the MITT population. MITT Among Survivors: patients from the MITT population who did not die on study or who died and were positive (indeterminate or failure)for the study endpoint being analyzed prior to death (as determined by EC adjudication).
Period Title: Overall Study
STARTED	907	908
COMPLETED	690	720
NOT COMPLETED	217	188

Baseline Characteristics

Arm/Group Title	Omiganan 1% Gel	Povidone-Iodine	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	907	908	1815
Age (Count of Participants)
<=18 years	1 0.1%	7 0.8%	8 0.4%
Between 18 and 65 years	488 53.8%	499 55%	987 54.4%
>=65 years	418 46.1%	402 44.3%	820 45.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.1 (16.82)	59.4 (17.17)	59.7 (17.00)
Sex: Female, Male (Count of Participants)
Female	350 38.6%	362 39.9%	712 39.2%
Male	557 61.4%	546 60.1%	1103 60.8%
Region of Enrollment (participants) [Number]
United States	364 40.1%	366 40.3%	730 40.2%
Europe	543 59.9%	542 59.7%	1085 59.8%

Outcome Measures

1. Primary Outcome

Title	Local Catheter Site Infection (LCSI)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Omiganan 1% Gel	Povidone-Iodine
Arm/Group Description
Measure Participants	793	818
Number [Events]	50	70

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omiganan 1% Gel, Povidone-Iodine
	Comments	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.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.082
	Comments	The primary null hypothesis was tested using the CMH chi-square test stratified region: North America or Europe. Alpha for this test will be 0.05, tow-tailed. No adjustment for multiplicity was performed.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Net percentage difference
	Estimated Value	2.25
	Confidence Interval	() 95%; -0.30 to 4.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Microbiologically-confirmed LCSI
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Omiganan 1% Gel	Povidone-Iodine
Arm/Group Description
Measure Participants	792	818
Number [Events]	31	62

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omiganan 1% Gel, Povidone-Iodine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Net percentage difference
	Estimated Value	3.67
	Confidence Interval	() 95%; 1.40 to 5.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Catheter Colonization (CC)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Omiganan 1% Gel	Povidone-Iodine
Arm/Group Description
Measure Participants	845	868
Number [Events]	369	478

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omiganan 1% Gel, Povidone-Iodine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Net percentage difference
	Estimated Value	11.40
	Confidence Interval	() 95%; 6.70 to 16.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.