COACT-1: Study of a Topical Gentamicin-Collagen Sponge Along With Systemic Antibiotic in Infected Diabetic Foot Ulcers

• Sponsor: Innocoll (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02427802
• Collaborator: (none)
• Enrollment: 612
• Locations: 86
• Arms: 3
• Duration (Months): 17.1
• Patients Per Site: 7.1
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This is a phase 3, randomized, controlled, blinded, multicenter study conducted in 3 parallel cohorts of diabetic patients with at least 1 infected foot ulcer. Patients will be randomized to receive 1 of 3 study treatments; systemic antibiotic therapy and standard ulcer care with either (A) daily application of a gentamicin-sponge, (B) daily application of a placebo-sponge or (C) no-sponge, in the ratio 2:1:1.

Patients will be treated for approximately 28 days and return to the clinic weekly for safety and efficacy assessments. After completing treatment, patients will return to the clinic for scheduled follow-up visits approximately 10, 30, 60 and 90 days after treatment is stopped.

Condition or Disease	Intervention/Treatment	Phase
Foot Ulcer, Diabetic; Infection	Drug: Gentamicin collagen sponge; Other: Placebo	Phase 3

Detailed Description

This is a phase 3, randomized, controlled, blinded, multicenter study conducted in 3 parallel cohorts of diabetic patients with at least 1 infected foot ulcer. Patients will be randomized using an electronic randomization system to receive 1 of 3 study treatments; systemic antibiotic therapy and standard ulcer care with either (A) daily application of a gentamicin-sponge, (B) daily application of a placebo-sponge or (C) no-sponge, in the ratio 2:1:1. The investigator will be blinded to the patient's treatment group assignment and patients randomized to one of the 2 sponge groups will be blinded as to whether the sponge is active or placebo.

If a patient has multiple infected ulcers, the assigned treatment will be administered to all infected ulcers. The investigator will determine the highest severity ulcer to be used for all efficacy evaluations and will also determine the size and number of sponges (up to 4) that a patient will use in order to completely cover all infected ulcers. The investigator will prescribe an empiric systemic antibiotic therapy based on protocol instructions.

Patients will be treated for approximately 28 days and return to the clinic weekly for safety and efficacy assessments. The investigator will stop study treatment if a patient achieves clinical cure by or after the 3rd treatment visit (approximately study day 15). After completing treatment, patients will return to the clinic for scheduled follow-up visits or until ulcer closure. The final efficacy assessments used in the primary efficacy analyses will be obtained at the first follow-up visit approximately 10 days after treatment is stopped. The remaining follow-up visits will occur at approximately 30, 60 and 90 days after treatment is stopped when patients will be assessed for ulcer closure and any re-infection.

Study Design

• Study Type: Interventional
• Actual Enrollment: 612 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Randomized, Placebo-Controlled, Blinded Study to Investigate the Safety and Efficacy of a Topical Gentamicin-Collagen Sponge in Combination With Systemic Antibiotic Therapy in Diabetic Patients With an Infected Foot Ulcer
• Study Start Date: May 1, 2015
• Actual Primary Completion Date: Oct 1, 2016
• Actual Study Completion Date: Oct 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gentamicin sponge group Topical Gentamicin Collagen Sponge: Up to four collagen sponges each containing 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base) administered daily, with systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days.	Drug: Gentamicin collagen sponge; Up to 4 topical Gentamicin Collagen Sponges each containing 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base); Other Names: Cogenzia
Placebo Comparator: Placebo sponge group Matching placebo collagen sponge administered daily, with systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days.	Other: Placebo; Matching collagen sponge
No Intervention: No sponge group Systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days.

Outcome Measures

Primary Outcome Measures

1. Clinical Cure (Resolution of All Clinical Signs and Symptoms of Infection) [approximately 10 days after end of treatment]

   The primary efficacy variable is the percent of patients with a clinical outcome of clinical cure (Resolution of all clinical signs and symptoms of infection) at F/U visit 1

Secondary Outcome Measures

1. Clinical Cure and Baseline Pathogen Eradication (Resolution of All Clinical Signs and Symptoms of Infection) and Baseline Pathogen Eradication) [Approximately 10 days after end of treatment]

   Percent of patients with both a clinical outcome of clinical cure (Resolution of all clinical signs and symptoms of infection) and baseline pathogen eradication at F/U visit 1

2. Reinfection (Percent of Patients With Re-infection) [Approximately 90 days after end of treatment]

   Percent of patients with re-infection

3. Time to Clinical Cure [Approximately 10 days after end of treatment]

   Actual time to clinical cure (Resolution of all clinical signs and symptoms of infection)

4. Amputation (Percent of Patients That Have an Amputation Associated With the Target Ulcer) [Within approximately 90 days of end of treatment]

   Percent of patients that have an amputation associated with the target ulcer

5. Ulcer Closure (Percent of Patients With Target Ulcer Closure) [within approximately 30 days of end of treatment]

   Percent of patients with ulcer closure within approximately 30 days of end of treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Has diabetes mellitus, according to the American Diabetes Association (ADA) criteria.

• Has at least 1 skin ulcer located on or below the malleolus that presents with the following clinical manifestations of a moderate or severe infection based on the Infectious Disease Society of America guidelines for the "Diagnosis and Treatment of

Diabetic Foot Infections" (CID 2012; 54:132-173) (IDSA guidelines):

• has ≥ 2 manifestations of inflammation (local swelling or induration, erythema, local tenderness or pain, local warmth, purulent discharge (thick, opaque to white or sanguineous secretion)

• has ≥ 1 of the following characteristics: erythema > 2cm, or involving structures deeper than skin and subcutaneous tissues (e.g. abscess, osteomyelitis, septic arthritis, fasciitis) For patients with multiple infected ulcers, the ulcer with the highest Diabetic Foot Infection Wound score (DFI score) must be on or below the malleolus and all infected ulcers must be completely coverable using no more than 4 sponges (sponges cannot be cut).

• Has documented adequate arterial perfusion in the affected limb(s) (either palpable dorsalis pedis and posterior tibial pulses, or normal Doppler wave forms, a toe blood pressure ≥ 45 mm Hg or participation is approved by a vascular surgeon)

• Has received appropriate surgical intervention to remove all necrotic and infected bone if diagnosed with osteomyelitis.

• Has received appropriate surgical debridement to remove all gangrenous tissue.

Exclusion Criteria:

• Has a known history of hypersensitivity to gentamicin (or other aminoglycosides).

• Has a known or suspected hypersensitivity to bovine collagen.

• Has an ulcer infection which, based upon the patient's known history of hypersensitivity and/or as otherwise in the opinion of the investigator, cannot be adequately treated with at least one of the empiric systemic antibiotic regimens allowed by this protocol.

• Has an ulcer associated with prosthetic material or an implanted device.

• Has received any systemic or topical antibiotic therapy for any reason within 7 days of randomization unless it was administered to specifically treat the infected ulcer(s) and only within 36 hours of randomization.

• Requires or is likely to require treatment with any concomitant topical product or wound therapy before the first follow-up study visit.

• Is severely immunocompromised, or likely to become severely immunocompromised during the study, in the opinion of the investigator.

• Has a history of myasthenia gravis or other neurological condition where gentamicin use is contraindicated as determined by the investigator.

• Has a history of epilepsy.

• Has a history of alcohol or substance abuse in the past 12 months.

• Has an uncontrolled illness that, in the opinion of the investigator, is likely to cause the patient to be withdrawn from the trial or would otherwise interfere with interpreting the results of the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Anniston	Alabama	United States	36207
2		Mobile	Alabama	United States	36608
3		Mesa	Arizona	United States	85206
4		Phoenix	Arizona	United States	85032
5		Fayetteville	Arkansas	United States	72703
6		Jonesboro	Arkansas	United States	72401
7		Little Rock	Arkansas	United States	72205
8		Little Rock	Arkansas	United States	72212
9		Bakersfield	California	United States	93301
10		Chino	California	United States	91710
11		Corona	California	United States	92882
12		Fountain Valley	California	United States	36207
13		Fresno	California	United States	93720
14		Fresno	California	United States	93721
15		Fresno	California	United States	93722
16		Long Beach	California	United States	90822
17		Los Angeles	California	United States	90057
18		Oakland	California	United States	94609
19		San Francisco	California	United States	94115
20		Sylmar	California	United States	91342
21		Norwalk	Connecticut	United States	06851
22		Washington	District of Columbia	United States	20007
23		Clermont	Florida	United States	34711
24		Cooper City	Florida	United States	33024
25		Coral Gables	Florida	United States	33134
26		Coral Gables	Florida	United States	33146
27		DeLand	Florida	United States	32720
28		Fleming Island	Florida	United States	32003
29		Hialeah	Florida	United States	33012
30		Hialeah	Florida	United States	33016
31		Hollywood	Florida	United States	33024
32		Miami Lakes	Florida	United States	33016
33		Miami Springs	Florida	United States	33166
34		Miami	Florida	United States	33122
35		Miami	Florida	United States	33126
36		Miami	Florida	United States	33135
37		Miami	Florida	United States	33136
38		Miami	Florida	United States	33155
39		Miami	Florida	United States	33174
40		Miami	Florida	United States	33175
41		Miami	Florida	United States	33185
42		New Port Richey	Florida	United States	34653
43		Saint Petersburg	Florida	United States	33713
44		West Palm Beach	Florida	United States	33406
45		Weston	Florida	United States	33326
46		Augusta	Georgia	United States	30907
47		Columbus	Georgia	United States	31904
48		Marietta	Georgia	United States	30060
49		Idaho Falls	Idaho	United States	83404
50		Avon	Indiana	United States	46123
51		Mooresville	Indiana	United States	46158
52		Muncie	Indiana	United States	47304
53		Baltimore	Maryland	United States	21215
54		Phoenix	Maryland	United States	21131
55		Boston	Massachusetts	United States	02118
56		Flint	Michigan	United States	48504
57		Butte	Montana	United States	59701
58		Great Falls	Montana	United States	59405
59		Las Vegas	Nevada	United States	89101
60		North Brunswick	New Jersey	United States	08902
61		Somerset	New Jersey	United States	08873
62		Hopewell Junction	New York	United States	12533
63		New Windsor	New York	United States	12553
64		Durham	North Carolina	United States	27710
65		Lima	Ohio	United States	45801
66		Oklahoma City	Oklahoma	United States	73104
67		Oklahoma City	Oklahoma	United States	73139
68		Philadelphia	Pennsylvania	United States	19103
69		Philadelphia	Pennsylvania	United States	19106
70		Greenville	South Carolina	United States	29605
71		Myrtle Beach	South Carolina	United States	29572
72		West Columbia	South Carolina	United States	29169
73		Dallas	Texas	United States	75224
74		Houston	Texas	United States	77024
75		Lampasas	Texas	United States	76550
76		Lubbock	Texas	United States	79410
77		McAllen	Texas	United States	78501
78		North Richland Hills	Texas	United States	76180
79		San Antonio	Texas	United States	78209
80		San Antonio	Texas	United States	78224
81		San Antonio	Texas	United States	78229
82		Sugar Land	Texas	United States	77479
83		Webster	Texas	United States	77598
84		Norfolk	Virginia	United States	23507
85		Virginia Beach	Virginia	United States	23464
86		Wenatchee	Washington	United States	98801

Sponsors and Collaborators

• Innocoll

Investigators

• Study Director: Nigel Jones, Vice President, Global Clinical Operations, Innocoll Pharmaceutical

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Innocoll
• ClinicalTrials.gov Identifier: NCT02427802
• Other Study ID Numbers: INN-TOP-004
• First Posted: Apr 28, 2015
• Last Update Posted: Aug 25, 2021
• Last Verified: Aug 1, 2021

• Additional relevant MeSH terms: Diabetic Foot; Foot Ulcer; Ulcer; Gentamicins

Study Results

Participant Flow

Arm/Group Title	Gentamicin Sponge Group	Placebo Sponge Group	No Sponge Group
Arm/Group Description	Topical Gentamicin Collagen Sponge: Up to four collagen sponges each containing 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base) administered daily, with systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days. Gentamicin collagen sponge: Up to 4 topical Gentamicin Collagen Sponges each containing 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base)	Matching placebo collagen sponge administered daily, with systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days. Placebo: Matching collagen sponge	Systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days.
Period Title: Overall Study
STARTED	305	154	153
COMPLETED	246	120	110
NOT COMPLETED	59	34	43

Baseline Characteristics

Arm/Group Title	Gentamicin Sponge Group	Placebo Sponge Group	No Sponge Group	Total
Arm/Group Description	Topical Gentamicin Collagen Sponge: Up to four collagen sponges each containing 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base) administered daily, with systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days. Gentamicin collagen sponge: Up to 4 topical Gentamicin Collagen Sponges each containing 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base)	Matching placebo collagen sponge administered daily, with systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days. Placebo: Matching collagen sponge	Systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days.	Total of all reporting groups
Overall Participants	305	154	153	612
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.6 (10.84)	57.1 (11.12)	56.7 (11.16)	57.3 (10.98)
Sex: Female, Male (Count of Participants)
Female	65 21.3%	47 30.5%	34 22.2%	146 23.9%
Male	240 78.7%	107 69.5%	119 77.8%	466 76.1%
Region of Enrollment (participants) [Number]
United States	305 100%	154 100%	153 100%	612 100%

Outcome Measures

1. Primary Outcome

Title	Clinical Cure (Resolution of All Clinical Signs and Symptoms of Infection)
Description	The primary efficacy variable is the percent of patients with a clinical outcome of clinical cure (Resolution of all clinical signs and symptoms of infection) at F/U visit 1
Time Frame	approximately 10 days after end of treatment

Outcome Measure Data

Analysis Population Description

modified intent to treat population consisted of randomized patients who received any dose of gentamicin-sponge or placebo-sponge or who were randomized to the no sponge arm, and who were not early-terminated for any of the treatment-unrelated reasons before F/U visit 1,

Arm/Group Title	Gentamicin Sponge Group	Placebo Sponge Group	No Sponge Group
Arm/Group Description	Topical Gentamicin Collagen Sponge: Up to four collagen sponges each containing 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base) administered daily, with systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days. Gentamicin collagen sponge: Up to 4 topical Gentamicin Collagen Sponges each containing 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base)	Matching placebo collagen sponge administered daily, with systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days. Placebo: Matching collagen sponge	Systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days.
Measure Participants	283	141	140
Count of Participants [Participants]	115 37.7%	64 41.6%	48 31.4%

2. Secondary Outcome

Title	Clinical Cure and Baseline Pathogen Eradication (Resolution of All Clinical Signs and Symptoms of Infection) and Baseline Pathogen Eradication)
Description	Percent of patients with both a clinical outcome of clinical cure (Resolution of all clinical signs and symptoms of infection) and baseline pathogen eradication at F/U visit 1
Time Frame	Approximately 10 days after end of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gentamicin Sponge Group	Placebo Sponge Group	No Sponge Group
Arm/Group Description	Topical Gentamicin Collagen Sponge: Up to four collagen sponges each containing 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base) administered daily, with systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days. Gentamicin collagen sponge: Up to 4 topical Gentamicin Collagen Sponges each containing 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base)	Matching placebo collagen sponge administered daily, with systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days. Placebo: Matching collagen sponge	Systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days.
Measure Participants	283	141	140
Count of Participants [Participants]	87 28.5%	47 30.5%	34 22.2%

3. Secondary Outcome

Title	Reinfection (Percent of Patients With Re-infection)
Description	Percent of patients with re-infection
Time Frame	Approximately 90 days after end of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gentamicin Sponge Group	Placebo Sponge Group	No Sponge Group
Arm/Group Description	Topical Gentamicin Collagen Sponge: Up to four collagen sponges each containing 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base) administered daily, with systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days. Gentamicin collagen sponge: Up to 4 topical Gentamicin Collagen Sponges each containing 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base)	Matching placebo collagen sponge administered daily, with systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days. Placebo: Matching collagen sponge	Systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days.
Measure Participants	283	141	140
Count of Participants [Participants]	12 3.9%	5 3.2%	2 1.3%

4. Secondary Outcome

Title	Time to Clinical Cure
Description	Actual time to clinical cure (Resolution of all clinical signs and symptoms of infection)
Time Frame	Approximately 10 days after end of treatment

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat Population

Arm/Group Title	Gentamicin Sponge Group	Placebo Sponge Group	No Sponge Group
Arm/Group Description	Topical Gentamicin Collagen Sponge: Up to four collagen sponges each containing 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base) administered daily, with systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days. Gentamicin collagen sponge: Up to 4 topical Gentamicin Collagen Sponges each containing 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base)	Matching placebo collagen sponge administered daily, with systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days. Placebo: Matching collagen sponge	Systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days.
Measure Participants	140	75	59
Median (95% Confidence Interval) [Days]	41	33	46

5. Secondary Outcome

Title	Amputation (Percent of Patients That Have an Amputation Associated With the Target Ulcer)
Description	Percent of patients that have an amputation associated with the target ulcer
Time Frame	Within approximately 90 days of end of treatment

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat Population

Arm/Group Title	Gentamicin Sponge Group	Placebo Sponge Group	No Sponge Group
Arm/Group Description	Topical Gentamicin Collagen Sponge: Up to four collagen sponges each containing 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base) administered daily, with systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days. Gentamicin collagen sponge: Up to 4 topical Gentamicin Collagen Sponges each containing 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base)	Matching placebo collagen sponge administered daily, with systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days. Placebo: Matching collagen sponge	Systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days.
Measure Participants	283	141	140
Count of Participants [Participants]	2 0.7%	3 1.9%	5 3.3%

6. Secondary Outcome

Title	Ulcer Closure (Percent of Patients With Target Ulcer Closure)
Description	Percent of patients with ulcer closure within approximately 30 days of end of treatment
Time Frame	within approximately 30 days of end of treatment

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat Population

Arm/Group Title	Gentamicin Sponge Group	Placebo Sponge Group	No Sponge Group
Arm/Group Description	Topical Gentamicin Collagen Sponge: Up to four collagen sponges each containing 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base) administered daily, with systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days. Gentamicin collagen sponge: Up to 4 topical Gentamicin Collagen Sponges each containing 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base)	Matching placebo collagen sponge administered daily, with systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days. Placebo: Matching collagen sponge	Systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days.
Measure Participants	283	141	140
Count of Participants [Participants]	67 22%	32 20.8%	29 19%

Adverse Events

Time Frame	approximately 28 days
Arm/Group Title	Gentamicin Sponge Group		Placebo Sponge Group		No Sponge Group
Arm/Group Description	Topical Gentamicin Collagen Sponge: Up to four collagen sponges each containing 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base) administered daily, with systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days. Gentamicin collagen sponge: Up to 4 topical Gentamicin Collagen Sponges each containing 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base)		Matching placebo collagen sponge administered daily, with systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days. Placebo: Matching collagen sponge		Systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days.
All Cause Mortality
	Gentamicin Sponge Group		Placebo Sponge Group		No Sponge Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/305 (0%)		4/154 (2.6%)		1/153 (0.7%)
Serious Adverse Events
	Gentamicin Sponge Group		Placebo Sponge Group		No Sponge Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/305 (14.4%)		22/154 (14.3%)		26/153 (17%)
Blood and lymphatic system disorders
cardiac failure congestive	4/305 (1.3%)	4	1/154 (0.6%)	1	0/153 (0%)	0
anaemia	2/305 (0.7%)	2	0/154 (0%)	0	0/153 (0%)	0
Cardiac disorders
cardiac arrest	0/305 (0%)	0	2/154 (1.3%)	2	0/153 (0%)	0
coronary artery disease	1/305 (0.3%)	1	1/154 (0.6%)	1	0/153 (0%)	0
acute myocardial infarction	0/305 (0%)	0	1/154 (0.6%)	1	0/153 (0%)	0
angina pectoris	0/305 (0%)	0	0/154 (0%)	0	1/153 (0.7%)	1
cardiac failure acute	1/305 (0.3%)	1	0/154 (0%)	0	0/153 (0%)	0
mitral valve incompetence	0/305 (0%)	0	1/154 (0.6%)	1	0/153 (0%)	0
myocardial infarction	0/305 (0%)	0	1/154 (0.6%)	1	0/153 (0%)	0
pericardial effusion	0/305 (0%)	0	1/154 (0.6%)	1	0/153 (0%)	0
ventricular tachycardia	1/305 (0.3%)	1	0/154 (0%)	0	0/153 (0%)	0
Gastrointestinal disorders
diabetic gastroparesis	1/305 (0.3%)	1	0/154 (0%)	0	0/153 (0%)	0
impaired gastric emptying	1/305 (0.3%)	1	0/154 (0%)	0	0/153 (0%)	0
General disorders
asthenia	0/305 (0%)	0	1/154 (0.6%)	1	0/153 (0%)	0
chest pain	1/305 (0.3%)	1	0/154 (0%)	0	0/153 (0%)	0
death	0/305 (0%)	0	0/154 (0%)	0	1/153 (0.7%)	1
device extrusion	0/305 (0%)	0	0/154 (0%)	0	1/153 (0.7%)	1
non-cardiac chest pain	1/305 (0.3%)	1	0/154 (0%)	0	0/153 (0%)	0
hip fracture	1/305 (0.3%)	1	0/154 (0%)	0	0/153 (0%)	0
Hepatobiliary disorders
cholecystitis acute	0/305 (0%)	0	0/154 (0%)	0	1/153 (0.7%)	1
Infections and infestations
osteomyelitis	7/305 (2.3%)	7	4/154 (2.6%)	4	7/153 (4.6%)	7
infected skin ulcer	7/305 (2.3%)	7	1/154 (0.6%)	1	4/153 (2.6%)	4
cellulitis	4/305 (1.3%)	4	1/154 (0.6%)	1	2/153 (1.3%)	2
osteomyelitis acute	3/305 (1%)	3	1/154 (0.6%)	1	2/153 (1.3%)	2
sepsis	3/305 (1%)	3	1/154 (0.6%)	1	0/153 (0%)	0
abscess limb	1/305 (0.3%)	1	0/154 (0%)	0	2/153 (1.3%)	2
gangrene	1/305 (0.3%)	1	1/154 (0.6%)	1	0/153 (0%)	0
influenza	0/305 (0%)	0	1/154 (0.6%)	1	0/153 (0%)	0
localised infection	0/305 (0%)	0	1/154 (0.6%)	1	0/153 (0%)	0
osteomyelitis chronic	1/305 (0.3%)	1	0/154 (0%)	0	0/153 (0%)	0
post procedural infection	0/305 (0%)	0	0/154 (0%)	0	1/153 (0.7%)	1
postoperative wound infection	0/305 (0%)	0	1/154 (0.6%)	1	0/153 (0%)	0
streptococcal bacteraemia	0/305 (0%)	0	0/154 (0%)	0	1/153 (0.7%)	1
Injury, poisoning and procedural complications
head injury	0/305 (0%)	0	1/154 (0.6%)	1	0/153 (0%)	0
limb injury	0/305 (0%)	0	0/154 (0%)	0	1/153 (0.7%)	1
stab wound	1/305 (0.3%)	1	0/154 (0%)	0	0/153 (0%)	0
Metabolism and nutrition disorders
decreased appetite	1/305 (0.3%)	1	0/154 (0%)	0	0/153 (0%)	0
diabetes mellitus inadequate cotnrol	1/305 (0.3%)	1	0/154 (0%)	0	0/153 (0%)	0
diabetic ketoacidosis	0/305 (0%)	0	0/154 (0%)	0	1/153 (0.7%)	1
hypokalaemia	1/305 (0.3%)	1	0/154 (0%)	0	0/153 (0%)	0
hyponatraemia	1/305 (0.3%)	1	0/154 (0%)	0	0/153 (0%)	0
metabolic acidosis	0/305 (0%)	0	1/154 (0.6%)	1	0/153 (0%)	0
type 2 diabetes mellitus	0/305 (0%)	0	0/154 (0%)	0	1/153 (0.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Mueller's mixed tumour	0/305 (0%)	0	0/154 (0%)	0	1/153 (0.7%)	1
Nervous system disorders
syncope	2/305 (0.7%)	2	0/154 (0%)	0	0/153 (0%)	0
diabetic hyperosmolar coma	1/305 (0.3%)	1	0/154 (0%)	0	0/153 (0%)	0
seizure	1/305 (0.3%)	1	0/154 (0%)	0	1/153 (0.7%)	1
transient ischaemic attack	1/305 (0.3%)	1	0/154 (0%)	0	0/153 (0%)	0
Psychiatric disorders
mental status changes	0/305 (0%)	0	1/154 (0.6%)	1	0/153 (0%)	0
suicidal ideation	1/305 (0.3%)	1	0/154 (0%)	0	0/153 (0%)	0
Renal and urinary disorders
acute kidney injury	2/305 (0.7%)	2	1/154 (0.6%)	1	2/153 (1.3%)	2
chronic kidney disease	2/305 (0.7%)	2	0/154 (0%)	0	1/153 (0.7%)	1
haematuria	1/305 (0.3%)	1	0/154 (0%)	0	0/153 (0%)	0
Reproductive system and breast disorders
penile necrosis	1/305 (0.3%)	1	0/154 (0%)	0	0/153 (0%)	0
Respiratory, thoracic and mediastinal disorders
acute respiratory failure	1/305 (0.3%)	1	1/154 (0.6%)	1	0/153 (0%)	0
chronic obstructive pulmonary disease	0/305 (0%)	0	2/154 (1.3%)	2	0/153 (0%)	0
pulmonay embolism	0/305 (0%)	0	0/154 (0%)	0	1/153 (0.7%)	1
pulmonary mass	1/305 (0.3%)	1	0/154 (0%)	0	0/153 (0%)	0
Skin and subcutaneous tissue disorders
skin ulcer	3/305 (1%)	3	1/154 (0.6%)	1	0/153 (0%)	0
decubitus ulcer	1/305 (0.3%)	1	0/154 (0%)	0	0/153 (0%)	0
Vascular disorders
hypotension	0/305 (0%)	0	1/154 (0.6%)	1	0/153 (0%)	0
peripheral ischaemia	0/305 (0%)	0	1/154 (0.6%)	1	0/153 (0%)	0
peripheral vascular disorder	0/305 (0%)	0	0/154 (0%)	0	1/153 (0.7%)	1
Other (Not Including Serious) Adverse Events
	Gentamicin Sponge Group		Placebo Sponge Group		No Sponge Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	135/305 (44.3%)		72/154 (46.8%)		65/153 (42.5%)
Ear and labyrinth disorders
Vertigo	12/305 (3.9%)	12	4/154 (2.6%)	4	3/153 (2%)	3
Gastrointestinal disorders
Nausea	22/305 (7.2%)	22	13/154 (8.4%)	13	6/153 (3.9%)	6
Diarrhoea	18/305 (5.9%)	18	3/154 (1.9%)	3	2/153 (1.3%)	2
Vomiting	7/305 (2.3%)	7	6/154 (3.9%)	6	2/153 (1.3%)	2
Constipation	2/305 (0.7%)	2	2/154 (1.3%)	2	3/153 (2%)	3
Immune system disorders
Drug Hypersensitivity	3/305 (1%)	3	1/154 (0.6%)	1	3/153 (2%)	3
Infections and infestations
infected skin ulcer	23/305 (7.5%)	23	11/154 (7.1%)	11	8/153 (5.2%)	8
Osteomyelitis	10/305 (3.3%)	10	8/154 (5.2%)	8	10/153 (6.5%)	10
Cellulitis	7/305 (2.3%)	7	4/154 (2.6%)	4	4/153 (2.6%)	4
Urinary Tract Infection	3/305 (1%)	3	4/154 (2.6%)	4	4/153 (2.6%)	4
Sepsis	6/305 (2%)	6	2/154 (1.3%)	2	0/153 (0%)	0
Upper Respiratory tract infection	3/305 (1%)	3	1/154 (0.6%)	1	3/153 (2%)	3
Injury, poisoning and procedural complications
Fall	5/305 (1.6%)	5	7/154 (4.5%)	7	1/153 (0.7%)	1
Laceration	1/305 (0.3%)	1	3/154 (1.9%)	3	3/153 (2%)	3
Skin abrasion	2/305 (0.7%)	2	1/154 (0.6%)	1	4/153 (2.6%)	4
Metabolism and nutrition disorders
Type 2 diabetes Mellitus	1/305 (0.3%)	1	1/154 (0.6%)	1	3/153 (2%)	3
Musculoskeletal and connective tissue disorders
Pain in extremity	4/305 (1.3%)	4	4/154 (2.6%)	4	0/153 (0%)	0
Renal and urinary disorders
Acute Kidney Injury	8/305 (2.6%)	8	4/154 (2.6%)	4	3/153 (2%)	3
Skin and subcutaneous tissue disorders
skin ulcer	26/305 (8.5%)	26	9/154 (5.8%)	9	11/153 (7.2%)	11
Blister	6/305 (2%)	6	2/154 (1.3%)	2	0/153 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Results of the multicenter study had to be published prior to the publication of any site specific data.