Diabetic Foot Ulcer
Conditions
Brief summary
This study is a prospective comparative study to determine if an Iodine Gel (Iodosorb◊) is better than standard dressing (Solosite◊ gel) in disruption of biofilm (small microorganism bacteria similar to plaque on teeth) on the wound bed diabetic foot ulcers. ◊ Trademark of Smith & Nephew
Detailed description
IODOSORB gel is a cadexomer iodine product indicated for use in wet ulcers and wounds. As the use of IODOSORB has an anti-microbial effect and removes exudate continuously from the wound, a reduction in pain, odour, oedema, exudate, pus and debris, and microbial load including biofilm can be achieved, hence providing an environment conducive to the normal healing process. While evidence exists to support the use of IODOSORB in diabetic foot ulcers (DFUs) for the reduction of planktonic bacteria, little evidence exits for the effect of any topical therapy on non-planktonic or biofilm bacteria in-vivo. The aim of this study is to explore the effects of IODOSORB on biofilm in the wound, wound healing, and associated factors, such as odour, pain, and reduction of slough.
Interventions
DEVICEIodosorb
Cadexomer iodine gel
DEVICESolosite gel
Hydrogel
Sponsors
Smith & Nephew, Inc.
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
1. The patient is able to understand the study and is willing to consent to the study. 2. The patient consents to the ongoing use of their de-identified photos by the Sponsor for purposes outside of this study. 3. The patient must be at least 18 years of age. 4. Males and females - provided they are not pregnant or lactating and if of reproductive age are using contraception. 5. The patient has presented with a DFU which, according to the clinical judgement of the Investigator, has a suspected biofilm 6. The patient has a DFU of Grade 1 or 2 according to the Meggit-Wagner scale. Grade 1 - Superficial ulcers limited to the dermis Grade 2 - Ulcers are transdermal with exposed bone or tendon, and without osteomyelitis or abscess formation 7. The patient's ulcer is suitable to be dressed with IODOSORB or SOLOSITE. 8. The patient has an ABPI \>0.49; or toe pressure \>50mmHg.
Exclusion criteria
1. Patients with a known history of poor compliance with medical treatment. 2. Patients who have participated in this study previously and who healed or were withdrawn. 3. Patients who are participating in any other clinical study. 4. Patients that have received continuous treatment with Iodosorb (on any wound) in the past 8 weeks (Iodosorb must not be continuously used for more 3 months) or whose reference ulcer has been treated with Iodosorb in the past 2 weeks. 5. Patients with a history of any thyroid disorders, e.g. Hashimoto's thyroiditis, Graves disease or non-toxic nodular goitre. 6. Patients undergoing treatment with mercurial antiseptics, taurolidine or lithium. 7. Patients with a known sensitivity to iodine or any of the other ingredients in IODOSORB, SOLOSITE or ALLEVYN Non-adhesive 8. Patients with severe renal impairment 9. Patients with an ulcer less than 3cm diameter. 10. Patients with an ulcer that is not exuding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Within-patient Change From Baseline in Log^10 Biofilm-protected Bacteria Count (Colony Forming Units [Cfu]/Gram[g]) | Baseline to Week 4 | The primary variable was the within-patient change from Baseline in log\^10 biofilm-protected bacteria count from Baseline (initial assessment) to Week 4, as measured by curettage. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage (%) Change in Ulcer Area | Baseline up through Week 4 +/- 4 days or End of Study Visit, up to 32 days | Overall percentage (%) of change in ulcer area from Baseline to final visit for the Iodosorb and Solosite arms. |
| Ulcer Depth Measurements at Each Study Visit | Baseline up through Week 4 +/- 4 days or End of Study Visit, up to 32 days | Calculated median/range measurements of the reference ulcer depth (mm) at each study visit as well as overall study completion ulcer depth measurements were assessed for the Iodosorb and Solosite arms. The ulcer depth as measured by inserting the cotton applicator into the deepest part of the ulcer and measuring from the tip of the applicator to the level of the skin surface. |
| Percentage (%) Change in Ulcer Depth | Baseline up through Week 4 +/- 4 days or End of Study Visit, up to 32 days | Overall percentage (%) of change in ulcer depth from Baseline to final visit for the Iodosorb and Solosite arms. |
| Ulcer Area Measurements at Each Study Visit | Baseline up through Week 4 +/- 4 days or End of Study Visit, up to 32 days | Calculated overall median/range measurements of the reference ulcer area (cm\^2) at each study visit as well as overall study completion ulcer area measurements were assessed for the Iodosorb and Solosite arms. The ulcer area was calculated as area = length x width x 0.785. |
| Percentage (%) Change in Ulcer Volume | Baseline up through Week 4 +/- 4 days or End of Study Visit, up to 32 days | Overall percentage (%) of change in ulcer volume from Baseline to final visit for the Iodosorb and Solosite arms. |
| Presence of Biofilm by Clinical Judgment Versus Presence of Biofilm by Laboratory Test | Baseline, Week 2, Week 4 | Assessment of subjects clinically judged to have biofilm present on the wound. The presumption of biofilm was determined on visual appearance to the Investigator and compared to microbial swab laboratory test confirmation. Biofilm is a microbial colony encased in a polysaccharide matrix which can become attached to a wound surface and prevent healing. Biofilm can appear as a shiny or slimy layer (clear to yellowish in appearance) on a wound bed. |
| Ulcer Volume Measurements at Each Study Visit | Baseline up through Week 4 +/- 4 days or End of Study Visit, up to 32 days | Calculated median/range measurements of the ulcer volume (cm\^3) at each study visit as well as overall study completion ulcer volume measurements were assessed for the Iodosorb and Solosite arms. The ulcer volume was measured by calculating the length x width x depth of the ulcer. |
Countries
United States
Participant flow
Recruitment details
Initial assessment screening/enrollment occurred at a single site in the United States from 05Aug2014 to 11Sep2015. Eligible participants were randomized to receive either IODOSORB or SOLOSITE for up to 4 weeks (28 +/- 4 days) or until reference ulcer closure (whichever came first).
Participants by arm
| Arm | Count |
|---|---|
| SOLOSITE Gel Hydrogel with preservatives, used to create a moist wound environment.
SOLOSITE Gel: Hydrogel | 7 |
| IODOSORB Cadexomer iodine gel
IODOSORB: Cadexomer iodine gel | 7 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Enrollment Hold | 1 | 1 |
| Overall Study | Previously Enrolled | 0 | 1 |
Baseline characteristics
| Characteristic | SOLOSITE Gel | IODOSORB | Total |
|---|---|---|---|
| Age, Continuous | 62.7 years STANDARD_DEVIATION 8.2 | 51.4 years STANDARD_DEVIATION 9 | 57 years STANDARD_DEVIATION 10.2 |
| Baseline Reference Ulcer: Area (centimeters squared [cm^2]) | 9.4 cm^2 | 8.5 cm^2 | 9 cm^2 |
| Baseline Reference Ulcer: Depth (millimeters [mm]) | 4 mm | 2 mm | 3 mm |
| Height (centimeters [cm]) | 178.9 cm STANDARD_DEVIATION 12.6 | 179.9 cm STANDARD_DEVIATION 9.9 | 179.4 cm STANDARD_DEVIATION 10.9 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Reference Ulcer: Volume (centimeters cubed [cm^3]) | 3.8 cm^3 | 1.7 cm^3 | 2.3 cm^3 |
| Region of Enrollment United States | 7 Participants | 7 Participants | 14 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 14 Participants |
| Weight (kilograms [kg]) | 91.9 kg STANDARD_DEVIATION 31.5 | 114.5 kg STANDARD_DEVIATION 37.8 | 103.2 kg STANDARD_DEVIATION 35.5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 10 |
| other Total, other adverse events | 1 / 9 | 1 / 10 |
| serious Total, serious adverse events | 1 / 9 | 1 / 10 |
Outcome results
Primary
Within-patient Change From Baseline in Log^10 Biofilm-protected Bacteria Count (Colony Forming Units [Cfu]/Gram[g])
The primary variable was the within-patient change from Baseline in log\^10 biofilm-protected bacteria count from Baseline (initial assessment) to Week 4, as measured by curettage.
Time frame: Baseline to Week 4
Population: The reporting of this outcome measure is based on the confirmed biofilm analysis set, defined as all subjects admitted to the study and for which the presence of biofilm was confirmed using curettage samples. Week 4 data were included for a total of 12 subjects (SOLOSITE N= 6; IODOSORB N = 6) in the biofilm analysis set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Solosite Gel | Within-patient Change From Baseline in Log^10 Biofilm-protected Bacteria Count (Colony Forming Units [Cfu]/Gram[g]) | 0.8 log^10 CFU/g |
| Iodosorb | Within-patient Change From Baseline in Log^10 Biofilm-protected Bacteria Count (Colony Forming Units [Cfu]/Gram[g]) | 1.0 log^10 CFU/g |
Secondary
Percentage (%) Change in Ulcer Area
Overall percentage (%) of change in ulcer area from Baseline to final visit for the Iodosorb and Solosite arms.
Time frame: Baseline up through Week 4 +/- 4 days or End of Study Visit, up to 32 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Solosite Gel | Percentage (%) Change in Ulcer Area | 29.4 percent change | Standard Deviation 23.1 |
| Iodosorb | Percentage (%) Change in Ulcer Area | 24.8 percent change | Standard Deviation 39 |
Secondary
Percentage (%) Change in Ulcer Depth
Overall percentage (%) of change in ulcer depth from Baseline to final visit for the Iodosorb and Solosite arms.
Time frame: Baseline up through Week 4 +/- 4 days or End of Study Visit, up to 32 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Solosite Gel | Percentage (%) Change in Ulcer Depth | -7.9 percent change | Standard Deviation 143.8 |
| Iodosorb | Percentage (%) Change in Ulcer Depth | -38.1 percent change | Standard Deviation 165.2 |
Secondary
Percentage (%) Change in Ulcer Volume
Overall percentage (%) of change in ulcer volume from Baseline to final visit for the Iodosorb and Solosite arms.
Time frame: Baseline up through Week 4 +/- 4 days or End of Study Visit, up to 32 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Solosite Gel | Percentage (%) Change in Ulcer Volume | 15.0 percent change | Standard Deviation 119.1 |
| Iodosorb | Percentage (%) Change in Ulcer Volume | 21.5 percent change | Standard Deviation 57.5 |
Secondary
Presence of Biofilm by Clinical Judgment Versus Presence of Biofilm by Laboratory Test
Assessment of subjects clinically judged to have biofilm present on the wound. The presumption of biofilm was determined on visual appearance to the Investigator and compared to microbial swab laboratory test confirmation. Biofilm is a microbial colony encased in a polysaccharide matrix which can become attached to a wound surface and prevent healing. Biofilm can appear as a shiny or slimy layer (clear to yellowish in appearance) on a wound bed.
Time frame: Baseline, Week 2, Week 4
Population: The reporting of this outcome measure is based on the confirmed biofilm analysis set, defined as all subjects admitted to the study and for which the presence of biofilm was confirmed using curettage samples (Initial Visit: N=14; Week 1: N=14; Week 2: N=13; Week 3: N=12; Week 4: N=12; Study Completion: N=14).
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Solosite Gel | Presence of Biofilm by Clinical Judgment Versus Presence of Biofilm by Laboratory Test | Biofilm Present by Clinical Judgment at Baseline | Yes | 7 Participants |
| Solosite Gel | Presence of Biofilm by Clinical Judgment Versus Presence of Biofilm by Laboratory Test | Biofilm Present by Clinical Judgment at Week 2 | Yes | 6 Participants |
| Solosite Gel | Presence of Biofilm by Clinical Judgment Versus Presence of Biofilm by Laboratory Test | Biofilm Present by Clinical Judgment at Week 2 | No | 0 Participants |
| Solosite Gel | Presence of Biofilm by Clinical Judgment Versus Presence of Biofilm by Laboratory Test | Biofilm Present by Laboratory Test at Baseline | No | 0 Participants |
| Solosite Gel | Presence of Biofilm by Clinical Judgment Versus Presence of Biofilm by Laboratory Test | Biofilm Present by Laboratory Test at Week 4 | Yes | 5 Participants |
| Solosite Gel | Presence of Biofilm by Clinical Judgment Versus Presence of Biofilm by Laboratory Test | Biofilm Present by Laboratory Test at Week 2 | Yes | 6 Participants |
| Solosite Gel | Presence of Biofilm by Clinical Judgment Versus Presence of Biofilm by Laboratory Test | Biofilm Present by Laboratory Test at Week 4 | No | 1 Participants |
| Solosite Gel | Presence of Biofilm by Clinical Judgment Versus Presence of Biofilm by Laboratory Test | Biofilm Present by Laboratory Test at Baseline | Yes | 7 Participants |
| Solosite Gel | Presence of Biofilm by Clinical Judgment Versus Presence of Biofilm by Laboratory Test | Biofilm Present by Clinical Judgment at Week 4 | Yes | 5 Participants |
| Solosite Gel | Presence of Biofilm by Clinical Judgment Versus Presence of Biofilm by Laboratory Test | Biofilm Present by Laboratory Test at Week 2 | No | 0 Participants |
| Solosite Gel | Presence of Biofilm by Clinical Judgment Versus Presence of Biofilm by Laboratory Test | Biofilm Present by Clinical Judgment at Week 4 | No | 1 Participants |
| Solosite Gel | Presence of Biofilm by Clinical Judgment Versus Presence of Biofilm by Laboratory Test | Biofilm Present by Clinical Judgment at Baseline | No | 0 Participants |
| Iodosorb | Presence of Biofilm by Clinical Judgment Versus Presence of Biofilm by Laboratory Test | Biofilm Present by Clinical Judgment at Week 4 | No | 2 Participants |
| Iodosorb | Presence of Biofilm by Clinical Judgment Versus Presence of Biofilm by Laboratory Test | Biofilm Present by Clinical Judgment at Baseline | No | 0 Participants |
| Iodosorb | Presence of Biofilm by Clinical Judgment Versus Presence of Biofilm by Laboratory Test | Biofilm Present by Clinical Judgment at Week 2 | Yes | 5 Participants |
| Iodosorb | Presence of Biofilm by Clinical Judgment Versus Presence of Biofilm by Laboratory Test | Biofilm Present by Laboratory Test at Baseline | Yes | 7 Participants |
| Iodosorb | Presence of Biofilm by Clinical Judgment Versus Presence of Biofilm by Laboratory Test | Biofilm Present by Laboratory Test at Baseline | No | 0 Participants |
| Iodosorb | Presence of Biofilm by Clinical Judgment Versus Presence of Biofilm by Laboratory Test | Biofilm Present by Clinical Judgment at Baseline | Yes | 7 Participants |
| Iodosorb | Presence of Biofilm by Clinical Judgment Versus Presence of Biofilm by Laboratory Test | Biofilm Present by Laboratory Test at Week 2 | Yes | 6 Participants |
| Iodosorb | Presence of Biofilm by Clinical Judgment Versus Presence of Biofilm by Laboratory Test | Biofilm Present by Laboratory Test at Week 2 | No | 1 Participants |
| Iodosorb | Presence of Biofilm by Clinical Judgment Versus Presence of Biofilm by Laboratory Test | Biofilm Present by Clinical Judgment at Week 2 | No | 2 Participants |
| Iodosorb | Presence of Biofilm by Clinical Judgment Versus Presence of Biofilm by Laboratory Test | Biofilm Present by Laboratory Test at Week 4 | Yes | 4 Participants |
| Iodosorb | Presence of Biofilm by Clinical Judgment Versus Presence of Biofilm by Laboratory Test | Biofilm Present by Laboratory Test at Week 4 | No | 2 Participants |
| Iodosorb | Presence of Biofilm by Clinical Judgment Versus Presence of Biofilm by Laboratory Test | Biofilm Present by Clinical Judgment at Week 4 | Yes | 4 Participants |
Secondary
Ulcer Area Measurements at Each Study Visit
Calculated overall median/range measurements of the reference ulcer area (cm\^2) at each study visit as well as overall study completion ulcer area measurements were assessed for the Iodosorb and Solosite arms. The ulcer area was calculated as area = length x width x 0.785.
Time frame: Baseline up through Week 4 +/- 4 days or End of Study Visit, up to 32 days
Population: The reporting of this outcome measure is based on the confirmed biofilm analysis set, defined as all subjects admitted to the study and for which the presence of biofilm was confirmed using curettage samples (Initial Visit: N=14; Week 1: N=14; Week 2: N=13; Week 3: N=12; Week 4: N=12; Study Completion: N=14).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Solosite Gel | Ulcer Area Measurements at Each Study Visit | Week 1 Ulcer Area Measurement | 9.4 cm^2 |
| Solosite Gel | Ulcer Area Measurements at Each Study Visit | Week 3 Ulcer Area Measurement | 8.0 cm^2 |
| Solosite Gel | Ulcer Area Measurements at Each Study Visit | Week 4 Ulcer Area Measurement | 6.1 cm^2 |
| Solosite Gel | Ulcer Area Measurements at Each Study Visit | Baseline Ulcer Area Measurement | 9.4 cm^2 |
| Solosite Gel | Ulcer Area Measurements at Each Study Visit | Study Completion Ulcer Area Measurement | 5.5 cm^2 |
| Solosite Gel | Ulcer Area Measurements at Each Study Visit | Week 2 Ulcer Area Measurement | 8.1 cm^2 |
| Iodosorb | Ulcer Area Measurements at Each Study Visit | Study Completion Ulcer Area Measurement | 7.8 cm^2 |
| Iodosorb | Ulcer Area Measurements at Each Study Visit | Week 2 Ulcer Area Measurement | 7.8 cm^2 |
| Iodosorb | Ulcer Area Measurements at Each Study Visit | Baseline Ulcer Area Measurement | 8.5 cm^2 |
| Iodosorb | Ulcer Area Measurements at Each Study Visit | Week 3 Ulcer Area Measurement | 7.0 cm^2 |
| Iodosorb | Ulcer Area Measurements at Each Study Visit | Week 4 Ulcer Area Measurement | 6.8 cm^2 |
| Iodosorb | Ulcer Area Measurements at Each Study Visit | Week 1 Ulcer Area Measurement | 7.3 cm^2 |
Secondary
Ulcer Depth Measurements at Each Study Visit
Calculated median/range measurements of the reference ulcer depth (mm) at each study visit as well as overall study completion ulcer depth measurements were assessed for the Iodosorb and Solosite arms. The ulcer depth as measured by inserting the cotton applicator into the deepest part of the ulcer and measuring from the tip of the applicator to the level of the skin surface.
Time frame: Baseline up through Week 4 +/- 4 days or End of Study Visit, up to 32 days
Population: The reporting of this outcome measure is based on the confirmed biofilm analysis set, defined as all subjects admitted to the study and for which the presence of biofilm was confirmed using curettage samples (Initial Visit: N=14; Week 1: N=14; Week 2: N=13; Week 3: N=12; Week 4: N=12; Study Completion: N=14).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Solosite Gel | Ulcer Depth Measurements at Each Study Visit | Week 4 Ulcer Depth Measurement | 2.5 mm |
| Solosite Gel | Ulcer Depth Measurements at Each Study Visit | Baseline Ulcer Depth Measurement | 4 mm |
| Solosite Gel | Ulcer Depth Measurements at Each Study Visit | Week 1 Ulcer Depth Measurement | 3 mm |
| Solosite Gel | Ulcer Depth Measurements at Each Study Visit | Week 2 Ulcer Depth Measurement | 2.5 mm |
| Solosite Gel | Ulcer Depth Measurements at Each Study Visit | Week 3 Ulcer Depth Measurement | 2 mm |
| Solosite Gel | Ulcer Depth Measurements at Each Study Visit | Study Completion Ulcer Depth Measurement | 3 mm |
| Iodosorb | Ulcer Depth Measurements at Each Study Visit | Week 3 Ulcer Depth Measurement | 1.5 mm |
| Iodosorb | Ulcer Depth Measurements at Each Study Visit | Week 4 Ulcer Depth Measurement | 1.5 mm |
| Iodosorb | Ulcer Depth Measurements at Each Study Visit | Week 2 Ulcer Depth Measurement | 2 mm |
| Iodosorb | Ulcer Depth Measurements at Each Study Visit | Baseline Ulcer Depth Measurement | 2 mm |
| Iodosorb | Ulcer Depth Measurements at Each Study Visit | Study Completion Ulcer Depth Measurement | 2 mm |
| Iodosorb | Ulcer Depth Measurements at Each Study Visit | Week 1 Ulcer Depth Measurement | 2 mm |
Secondary
Ulcer Volume Measurements at Each Study Visit
Calculated median/range measurements of the ulcer volume (cm\^3) at each study visit as well as overall study completion ulcer volume measurements were assessed for the Iodosorb and Solosite arms. The ulcer volume was measured by calculating the length x width x depth of the ulcer.
Time frame: Baseline up through Week 4 +/- 4 days or End of Study Visit, up to 32 days
Population: The reporting of this outcome measure is based on the confirmed biofilm analysis set, defined as all subjects admitted to the study and for which the presence of biofilm was confirmed using curettage samples (Initial Visit: N=14; Week 1: N=14; Week 2: N=13; Week 3: N=12; Week 4: N=12; Study Completion: N=14).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Solosite Gel | Ulcer Volume Measurements at Each Study Visit | Week 1 Ulcer Volume Measurement | 3.3 cm^3 |
| Solosite Gel | Ulcer Volume Measurements at Each Study Visit | Week 3 Ulcer Volume Measurement | 1.7 cm^3 |
| Solosite Gel | Ulcer Volume Measurements at Each Study Visit | Baseline Ulcer Volume Measurement | 3.8 cm^3 |
| Solosite Gel | Ulcer Volume Measurements at Each Study Visit | Week 4 Ulcer Volume Measurement | 1.8 cm^3 |
| Solosite Gel | Ulcer Volume Measurements at Each Study Visit | Week 2 Ulcer Volume Measurement | 2.6 cm^3 |
| Solosite Gel | Ulcer Volume Measurements at Each Study Visit | Study Completion Ulcer Volume Measurement | 1.6 cm^3 |
| Iodosorb | Ulcer Volume Measurements at Each Study Visit | Week 2 Ulcer Volume Measurement | 1.3 cm^3 |
| Iodosorb | Ulcer Volume Measurements at Each Study Visit | Baseline Ulcer Volume Measurement | 1.7 cm^3 |
| Iodosorb | Ulcer Volume Measurements at Each Study Visit | Week 1 Ulcer Volume Measurement | 0.9 cm^3 |
| Iodosorb | Ulcer Volume Measurements at Each Study Visit | Study Completion Ulcer Volume Measurement | 1.1 cm^3 |
| Iodosorb | Ulcer Volume Measurements at Each Study Visit | Week 3 Ulcer Volume Measurement | 1.1 cm^3 |
| Iodosorb | Ulcer Volume Measurements at Each Study Visit | Week 4 Ulcer Volume Measurement | 1.1 cm^3 |