Diabetic Foot Ulcers
Conditions
Brief summary
The purpose of this study is to compare the safety and effectiveness of the dermaPACE Device to sham application, when administered in conjunction with standard treatments used in the treatment of DFUs.
Detailed description
The objective of this clinical study is to compare the safety and effectiveness of the dermaPACE (Pulsed Acoustic Cellular Expression) Device to sham application, when administered in conjunction with the standard of care, in the treatment of DFUs. Diabetic patients are susceptible to chronic foot ulcerations due to the effects of the diabetic's systemic disease halting the wound healing process. In the United States, 20.8 million people with active diabetes, and 41 million with pre-diabetic symptoms account for $132 billion dollars in healthcare costs per year. In 2002, 82,000 non-traumatic lower-limb amputations were performed on diabetics, corresponding to 60% of all lower limb amputations, usually preceded by a non-healing foot ulceration. Given the magnitude of this disease and the long-term effects and morbidity of amputation, DFUs require immediate and aggressive treatment to ascertain the best possible outcome for the diabetic patient. Despite the development of advanced wound care products, there is still a need to find the most effective treatment for reducing the time required to close a DFU. At any given time, 3-4% of diabetics (600,000 patients) have a foot ulcer, and $2.5 billion was spent in 2002 in the United States treating DFUs. The average cost for a single episode of a foot ulcer has been reported to be $4,595.00 to $28,691.00. Shock wave devices, which utilize acoustic pressure waves, have been used for about 30 years in urology for lithotripsy. In the last decade this technology has gained FDA approval to treat chronic plantar fasciitis and lateral epicondylitis conditions that do not respond to conservative treatments (OssaTron® SANUWAVE, manufacturer). Further, clinical reports have indicated efficacy in treating many other orthopedic conditions including pseudoarthroses, calcification of the joints and avascular necrosis. This technology has also been shown to promote healing in several wound-healing applications, and it is worthwhile to continue to seek the full potential of this technology in wound healing. Acoustic pressure waves initiate a biological response at the cellular level-stimulating production of angiogenic growth factors, including endothelial nitric oxide synthase (ENOS), vascular endothelial growth factor (VEGF), and proliferating cell nuclear antigen (PCNA). These factors are important components of the normal wound healing process. This cellular activation and growth factor expression stimulated by acoustic pressure wave treatment could play a decisive role in overcoming cell quiescence and increasing growth factor titers to levels sufficient to overcome proteases. This leads to the in-growing of newly formed vessels, and the increased cellular proliferation and tissue regeneration needed to heal a wound. Clinical publications have recently reported the pressure wave induced mechanism described above can initiate and accelerate healing in burns, traumatic wounds and reconstructive skin flaps, and diabetic wounds. A pilot study using the dermaPACE device, performed in nine diabetic subjects with chronic leg ulcers has shown that this technology in patients with a history of chronic ulcers may achieve wound closure. Treatment with dermaPACE has the added benefits of being non-invasive and devoid of significant clinical side effects. Therefore, the objective of this study is to examine the safety and effectiveness of the dermaPACE acoustic pressure wave treatment device in combination with standard of care for the treatment of foot ulcers in diabetic patients. The dermaPACE should offer an improved non-invasive standard of care that may shorten an otherwise lengthy healing process and therefore make later operative measures unnecessary. Given that conservative therapy may not be effective, dermaPACE may become a preferable alternative that would carry minimal risk based on the expected clinical outcomes described in this protocol. dermaPACE may improve patient quality of life when conservative therapy is not effective as well as provide a cost savings for the health care system.
Interventions
DEVICEacoustical pulse energy (extracorporeal shockwave)
Acoustical pulse energy (extracorporeal shockwave) + Standard of care wound dressing.
OTHERSham
Non-energized (inactive - Sham) application + standard of care
Sponsors
SANUWAVE, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Major Inclusion Criteria: * Male or female ≥ 18 years of age * Diabetes mellitus * One or more chronic foot ulcers (only one will be treated) that are located in the ankle area or below that has persisted a minimum of 30 days prior to the Screening visit * HbA1c ≤ 12% * Diabetic Foot Ulcers ≥ 1 cm2 and ≤ 16 cm2 * Ulcer Grade I or II, Stage A according to the University of Texas Diabetic Wound Classification system * Ankle Brachial Index (ABI) ≥ 0.7 and ≤ 1.2, OR toe pressure \> 50 mmHg, OR tcPO2\> 40 mmHg. Major
Exclusion criteria
* Subject is morbidly obese (Body Mass Index ≥ 40) * Subjects on dialysis * Diagnosis of foot ulcer involving osteomyelitis * Has evidence of prior ulcer in the same area * Multiple diabetic foot ulcers on the foot that either are connected by fistulas or are within 5 cm of the target ulcer * Subject's foot ulcer intended for study application has decreased in volume by 50% or more at the end of the two-week Run-in period as compared to the Screening visit.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Primary Variable for Effectiveness of the dermaPACE Device Will be Assessed by Comparing the Incidence of Complete Wound Closure of the dermaPACE and Control Groups 12 Weeks Post Initial Application. | 12 weeks post initial application |
Secondary
| Measure | Time frame |
|---|---|
| Time to Wound Closure, Wound Closure Area and Volume Between Active and Control 12 Weeks Post Initial Application, Subject Pain Assessment Between Active and Control 24 Weeks Post Initial Application | 12 weeks post initial application and 24 weeks post initial application |
Countries
Germany, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| dermaPACE Application + Standard of Care dermaPACE: dermaPACE + Standard of care wound dressing. | 107 |
| Non-energized (Inactive) Application + Standard of Care Sham: Sham treatment (non-energized, inactive device) + Standard of care wound dressing. | 99 |
| Total | 206 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 13 | 10 |
| Overall Study | Death | 2 | 1 |
| Overall Study | Lost to Follow-up | 3 | 5 |
| Overall Study | Physician Decision | 3 | 1 |
| Overall Study | PI tried alternative treatment | 1 | 3 |
| Overall Study | Withdrawal by Subject | 7 | 8 |
Baseline characteristics
| Characteristic | Non-energized (Inactive) Application + Standard of Care | Total | dermaPACE Application + Standard of Care |
|---|---|---|---|
| Age, Continuous | 56.2 years STANDARD_DEVIATION 9.4 | 58.3 years STANDARD_DEVIATION 9.9 | 60.4 years STANDARD_DEVIATION 10.4 |
| Region of Enrollment Germany | 3 participants | 5 participants | 2 participants |
| Region of Enrollment United Kingdom | 2 participants | 4 participants | 2 participants |
| Region of Enrollment United States | 94 participants | 197 participants | 103 participants |
| Sex: Female, Male Female | 16 Participants | 40 Participants | 24 Participants |
| Sex: Female, Male Male | 83 Participants | 166 Participants | 83 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 54 / 107 | 42 / 99 |
| serious Total, serious adverse events | 34 / 107 | 37 / 99 |
Outcome results
Primary
The Primary Variable for Effectiveness of the dermaPACE Device Will be Assessed by Comparing the Incidence of Complete Wound Closure of the dermaPACE and Control Groups 12 Weeks Post Initial Application.
Time frame: 12 weeks post initial application
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| dermaPACE Application + Standard of Care | The Primary Variable for Effectiveness of the dermaPACE Device Will be Assessed by Comparing the Incidence of Complete Wound Closure of the dermaPACE and Control Groups 12 Weeks Post Initial Application. | 22 participants |
| Non-energized (Inactive) Application + Standard of Care | The Primary Variable for Effectiveness of the dermaPACE Device Will be Assessed by Comparing the Incidence of Complete Wound Closure of the dermaPACE and Control Groups 12 Weeks Post Initial Application. | 15 participants |
Secondary
Time to Wound Closure, Wound Closure Area and Volume Between Active and Control 12 Weeks Post Initial Application, Subject Pain Assessment Between Active and Control 24 Weeks Post Initial Application
Time frame: 12 weeks post initial application and 24 weeks post initial application