Diabetic Foot Ulcer, Surgical Wound
Conditions
Keywords
topical oxygen, topical oxygen treatment, diabetic foot ulcer, non-healing wound, surgical site, pain, wound size, healing, infection
Brief summary
A Multicentre Randomized Controlled Trial to Investigate the Effect of Natrox Topical Oxygen Wound Therapy on the Healing rates of Diabetic Foot Ulcers.
Detailed description
Patients with diabetic foot ulcers will be enrolled into the trial at multiple wound care centers and hospital research centers across the United States of America. After qualifying per protocol, patients will be randomized to receive standard wound care or standard wound care plus Topical Oxygen Wound Therapy for their wounds. Patients will be monitored for 12 weeks. The primary comparator between the groups will be complete wound healing at 12 weeks, but other parameters will be assessed, such as pain, wound size reduction and infection status.
Interventions
DEVICENatrox® Oxygen Wound Therapy
A battery-operated device which delivers pure humidified oxygen to the wound bed through water electrolysis via a sterile oxygen delivery system.
Sponsors
SerenaGroup, Inc.
Inotec AMD Limited
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. Subjects are male or female, 18 years of age or older. At least 50% of the enrolled population must be ≥ 65 years of age. 2. Subjects with one of the following wounds: A. Diabetic foot ulcer present for greater than 4 weeks (documented in the medical record) but less than 12 months duration if being treated with active SOC. B. Minor amputation wound sites 3. Subject has clinical documentation of no visible wound improvement in the after 4 weeks of standard of care. Objectively, less than 40% healing in the past four weeks from the first treatment visit. 4. Study ulcer is a minimum of 0.5 cm2 and a maximum of 25 cm2 at first treatment visit 5. Subjects' wound score on ISDA tool is Grade 1 or 2. 6. The subject is able and willing to follow the protocol requirements 7. Subject has signed informed consent 8. Adequate circulation to the affected foot as demonstrated by a dorsum transcutaneous oxygen measurement (TCOM) or a skin perfusion pressure (SPP) measurement of ≥ 30 mmHg; an ABI between 0.7 and ≤ 1.3, or TBI of \>6 within 3 months of the first Screening Visit. 9. Females of childbearing potential must be willing to use acceptable methods of contraception (birth control pills, barriers, or abstinence). 10. The target ulcer has been offloaded for at least 14 days prior to randomization.
Exclusion criteria
1. Subject has a known life expectancy of \< 1 year 2. Subject or caregiver is unable to manage the Natrox® device (charge and change batteries daily) 3. Subject has ulcers that are completely necrotic or if the clinician feels it is clinically necessary to cover the wound surface in gel or creams that would prevent the transmission of oxygen to the wound surface. 4. Subject has major uncontrolled medical disorders such as serious cardiovascular, renal, liver or pulmonary disease, lupus, palliative care or sickle cell anemia. 5. Subject currently being treated for an active malignant disease or subjects with history of malignancy within the wound. 6. The Subject has other concurrent conditions that in the opinion of the Investigator may compromise subject safety 7. Known contraindications for the Natrox system 8. Known allergies to any of the Natrox system components 9. Concurrent participation in another clinical trial that involves an investigational drug or device that would interfere with this study. 10. Index ulcer has reduced in area by 20% or more after 2 weeks of standard of care from the first screening visit (S1) to the TV1/randomization visit. 11. Subject is pregnant or breast feeding. 12. Subjects with a history of more than two weeks treatment with immunosuppressants (including systemic corticosteroids \>10mg daily dose), cytotoxic chemotherapy, or application of topical steroids to the ulcer surface within one month prior to first Screening Visit, or who receive such medications during the screening period, or who are anticipated to require such medications during the course of the study. 13. Index ulcer has been previously treated with tissue engineered materials (e.g. Apligraf® or Dermagraft®) or other scaffold materials (e.g. Oasis, Matristem) within the last 30 days preceding the first treatment visit. 14. Affected extremity requiring hyperbaric oxygen during the trial or within 2 weeks of treatment visit 1. 15. Known HbA1C \>12% 16. An ulcer that has visible signs of improvement in the four weeks prior to randomization defined objectively as a 40% reduction in surface area in the four weeks prior to enrollment. 17. An ulcer that has healed by more than 20% in the 2 weeks prior to screening: historical run-in period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants That Achieve Complete Wound Closure During the Twelve Week Study and the Percentage Change in Participant Ulcer Size at 12 Weeks From Baseline. | Twelve (12) weeks from Time 0 | Photographic wound evaluation and measurements were conducted utilizing an AI-driven computerized planimetry imaging system (Tissue Analytics, Inc., Baltimore, MD USA).15 This system obtained both 2D and 3D assessments of the wound at each visit through a standardized mobile device; in addition, the lead investigator reviewed all digital images. |
| Percentage Reduction in Ulcer Area (cm^2). | Twelve (12) weeks from Time 0 | Wound size change over time using a wound imaging measurement system. Percentage change in ulcer area was calculated on the basis of area change from the start of the study to the final recorded value. Any healed ulcer was recorded as having achieved 100% reduction in area; positive values indicate a reduction in size over the 12-week period while negative values indicate that the ulcer increased in size. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Level of Pain of the Wound | Up to twelve (12) weeks from Time 0 | Does pain associated with the wound change over time using a Visual Analogue Scale Pain intensity of the reference DFU is to be assessed before any dressing changes or other ulcer manipulations at all screening and treatment visits. Subject will be asked to indicate a numerical value that best represents the pain intensity at ulcer site on a scale of 0 to 10 anchored by word descriptors at each end, as no pain on the left side and worst possible pain on the right side of the number line. The number 0 represent no pain, the number 5 represents moderate pain and the number 10 represents the worst possible pain. The subject indicates the level of pain intensity by selecting a number on the line that represents their perception of their current state. |
| Number of Adverse Events | Up to twelve (12) weeks from time 0 | Number of adverse events, such as infections, that are found associated with the study wound |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
Participants were initially screened and documentation was investigated. If all inclusion criteria were met, and the patient had a documented healing rate of \<20% reduction in wound size, the patients were entered into the 2-week run-in period. All patients were allocated to standard of care (SOC). At the baseline visit, if all inclusion and exclusion criteria were still applicable and the wound had not reduced in size by \>20%, the patient was then randomized.
Pre-assignment details
During run-in period patients either exceeded the percentage of acceptable healing per the protocol or had an adverse event preventing continuation in the trial.
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care Arm Patients in the standard of care arm will receive the standard care for their type of wound from their wound care centre. | 64 |
| Intervention Arm Patients in the intervention arm will receive standard of care plus Natrox® Oxygen Wound Therapy as treatment for their wound.
Natrox® Oxygen Wound Therapy: A battery-operated device which delivers 98% pure humidified oxygen to the wound bed through water electrolysis via a sterile oxygen delivery system. | 81 |
| Total | 145 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 4 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 0 | 3 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Standard of Care Arm | Intervention Arm | Total |
|---|---|---|---|
| Age, Continuous | 62.69 years | 64.2 years | 63 years |
| BMI | 31 Kg/m^2 | 30.8 Kg/m^2 | 30.9 Kg/m^2 |
| Current use Tobacco No | 51 Participants | 68 Participants | 119 Participants |
| Current use Tobacco Not declared | 2 Participants | 2 Participants | 4 Participants |
| Current use Tobacco Yes | 11 Participants | 11 Participants | 22 Participants |
| Diabetes duration | 18.33 years | 18.35 years | 18.34 years |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Puerto Rico | 8 participants | 5 participants | 13 participants |
| Region of Enrollment United States | 56 participants | 76 participants | 132 participants |
| Sex: Female, Male Female | 11 Participants | 26 Participants | 37 Participants |
| Sex: Female, Male Male | 53 Participants | 54 Participants | 107 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 64 | 1 / 81 |
| other Total, other adverse events | 13 / 64 | 19 / 81 |
| serious Total, serious adverse events | 8 / 64 | 6 / 81 |
Outcome results
Primary
Number of Participants That Achieve Complete Wound Closure During the Twelve Week Study and the Percentage Change in Participant Ulcer Size at 12 Weeks From Baseline.
Photographic wound evaluation and measurements were conducted utilizing an AI-driven computerized planimetry imaging system (Tissue Analytics, Inc., Baltimore, MD USA).15 This system obtained both 2D and 3D assessments of the wound at each visit through a standardized mobile device; in addition, the lead investigator reviewed all digital images.
Time frame: Twelve (12) weeks from Time 0
Population: Intention to treat
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard of Care Arm | Number of Participants That Achieve Complete Wound Closure During the Twelve Week Study and the Percentage Change in Participant Ulcer Size at 12 Weeks From Baseline. | Intention to treat-healed | 18 Participants |
| Standard of Care Arm | Number of Participants That Achieve Complete Wound Closure During the Twelve Week Study and the Percentage Change in Participant Ulcer Size at 12 Weeks From Baseline. | Per protocol-healed | 18 Participants |
| Intervention Arm | Number of Participants That Achieve Complete Wound Closure During the Twelve Week Study and the Percentage Change in Participant Ulcer Size at 12 Weeks From Baseline. | Intention to treat-healed | 36 Participants |
| Intervention Arm | Number of Participants That Achieve Complete Wound Closure During the Twelve Week Study and the Percentage Change in Participant Ulcer Size at 12 Weeks From Baseline. | Per protocol-healed | 36 Participants |
Primary
Percentage Reduction in Ulcer Area (cm^2).
Wound size change over time using a wound imaging measurement system. Percentage change in ulcer area was calculated on the basis of area change from the start of the study to the final recorded value. Any healed ulcer was recorded as having achieved 100% reduction in area; positive values indicate a reduction in size over the 12-week period while negative values indicate that the ulcer increased in size.
Time frame: Twelve (12) weeks from Time 0
Population: Intention to treat as well an Per protocol analysis was carried out.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care Arm | Percentage Reduction in Ulcer Area (cm^2). | Intention to treat - percentage reduction | 41.05 Percentage reduction | Standard Deviation 69.82 |
| Standard of Care Arm | Percentage Reduction in Ulcer Area (cm^2). | Per protocol-percentage reduction | 40.44 Percentage reduction | Standard Deviation 72.1 |
| Intervention Arm | Percentage Reduction in Ulcer Area (cm^2). | Intention to treat - percentage reduction | 46.38 Percentage reduction | Standard Deviation 100.24 |
| Intervention Arm | Percentage Reduction in Ulcer Area (cm^2). | Per protocol-percentage reduction | 70.18 Percentage reduction | Standard Deviation 45.5 |
Secondary
Level of Pain of the Wound
Does pain associated with the wound change over time using a Visual Analogue Scale Pain intensity of the reference DFU is to be assessed before any dressing changes or other ulcer manipulations at all screening and treatment visits. Subject will be asked to indicate a numerical value that best represents the pain intensity at ulcer site on a scale of 0 to 10 anchored by word descriptors at each end, as no pain on the left side and worst possible pain on the right side of the number line. The number 0 represent no pain, the number 5 represents moderate pain and the number 10 represents the worst possible pain. The subject indicates the level of pain intensity by selecting a number on the line that represents their perception of their current state.
Time frame: Up to twelve (12) weeks from Time 0
Population: VAS scores were taken weekly. On a scale of 0-10, 0 is least pain and 10 is the most pain
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard of Care Arm | Level of Pain of the Wound | Baseline | 2.02 score on a VAS 0-10 scale | Standard Deviation 2.57 |
| Standard of Care Arm | Level of Pain of the Wound | Twelve weeks of final visit if healed during study | 0.68 score on a VAS 0-10 scale | Standard Deviation 1.43 |
| Intervention Arm | Level of Pain of the Wound | Baseline | 1.81 score on a VAS 0-10 scale | Standard Deviation 2.53 |
| Intervention Arm | Level of Pain of the Wound | Twelve weeks of final visit if healed during study | 0.95 score on a VAS 0-10 scale | Standard Deviation 1.9 |
Secondary
Number of Adverse Events
Number of adverse events, such as infections, that are found associated with the study wound
Time frame: Up to twelve (12) weeks from time 0
Population: Adverse reactions were recorded and reported throughout the study as they occurred.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard of Care Arm | Number of Adverse Events | Relationship to the product/Unlikely | 1 Number of adverse events |
| Standard of Care Arm | Number of Adverse Events | Relationship to the product/ Possibly related | 1 Number of adverse events |
| Standard of Care Arm | Number of Adverse Events | Relationship to the product/unrelated | 30 Number of adverse events |
| Standard of Care Arm | Number of Adverse Events | Relationship to the product/ probably related | 0 Number of adverse events |
| Standard of Care Arm | Number of Adverse Events | Number of adverse events | 32 Number of adverse events |
| Intervention Arm | Number of Adverse Events | Relationship to the product/ probably related | 1 Number of adverse events |
| Intervention Arm | Number of Adverse Events | Number of adverse events | 41 Number of adverse events |
| Intervention Arm | Number of Adverse Events | Relationship to the product/unrelated | 37 Number of adverse events |
| Intervention Arm | Number of Adverse Events | Relationship to the product/ Possibly related | 1 Number of adverse events |
| Intervention Arm | Number of Adverse Events | Relationship to the product/Unlikely | 2 Number of adverse events |