Effectiveness of dermaPACE™ Device and Standard Treatment Compared to Standard Treatment Alone for Diabetic Foot Ulcers

• Sponsor: SANUWAVE, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00536744
• Collaborator: (none)
• Enrollment: 206
• Locations: 23
• Arms: 2
• Duration (Months): 35
• Patients Per Site: 9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Foot Ulcers	Device: acoustical pulse energy (extracorporeal shockwave); Other: Sham	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 206 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Use of the dermaPACE™ (Pulsed Acoustic Cellular Expression) Device in Conjunction With Standard of Care in the Treatment of Diabetic Foot Ulcers
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Active PACE application - 4 applications Application of acoustical pulse energy (extracorporeal shockwaves) to target ulcer + standard of care	Device: acoustical pulse energy (extracorporeal shockwave); Acoustical pulse energy (extracorporeal shockwave) + Standard of care wound dressing.; Other Names: dermaPACE
Sham Comparator: Inactive, non-energy application Non-energized (inactive - Sham)) application + standard of care	Other: Sham; Non-energized (inactive - Sham) application + standard of care

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix VA Health Care System	Phoenix	Arizona	United States	85012
2	HOPE Research Insititute	Phoenix	Arizona	United States	85050
3	Southern Arizona VA Healthcare System (SAVAHCS)	Tucson	Arizona	United States	85723
4	Center for Clinical Research	Castro Valley	California	United States	94115
5	Veterans Administration Long Beach Healthcare	Long Beach	California	United States	90822
6	Olive View - UCLA Medical Center	Sylmar	California	United States	91342
7	North American Center for Limb Preservation	New Haven	Connecticut	United States	06515
8	Fairfield County Foot Surgeons	Norwalk	Connecticut	United States	06851
9	Emory Orthopedic and Spine Center	Atlanta	Georgia	United States	30329
10	Northwestern Univ. Div. of Plastic Surgery	Chicago	Illinois	United States	60611
11	Boston Medical Center	Boston	Massachusetts	United States	02118
12	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
13	Mayo Clinic	Rochester	Minnesota	United States	55905
14	Center for Palliative Wound Care; Calvary Hospital	Bronx	New York	United States	10461
15	St. Vincent's Charity Hospital	Cleveland	Ohio	United States	44115
16	Ohio State University	Columbus	Ohio	United States	43221
17	Nashville Family Footcare	Nashville	Tennessee	United States	37203
18	Richard Galperin, DPM, PA	Dallas	Texas	United States	75224
19	Complete Family Foot Care	McAllen	Texas	United States	78501
20	Robert Wunderlich, DPM, PA	San Antonio	Texas	United States	78212
21	Aurora Health Care	Milwaukee	Wisconsin	United States	53215
22	Mathias Spital	Rheine		Germany	48431
23	Kings College Hospital	London		United Kingdom	SE59RS

Sponsors and Collaborators

• SANUWAVE, Inc.

Investigators

• Study Director: Daniel Jorgensen, MD, SANUWAVE, Inc.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Company Web Site

Publications

None provided.

• Responsible Party: SANUWAVE, Inc.
• ClinicalTrials.gov Identifier: NCT00536744
• Other Study ID Numbers: SAN07-DERM01
• First Posted: Sep 28, 2007
• Last Update Posted: Apr 14, 2014
• Last Verified: Mar 1, 2014

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

Study Results

Participant Flow

Arm/Group Title	dermaPACE Application + Standard of Care	Non-energized (Inactive) Application + Standard of Care
Arm/Group Description	dermaPACE application + standard of care dermaPACE: dermaPACE + Standard of care wound dressing.	Non-energized (inactive) application + standard of care Sham: Sham treatment + Standard of care wound dressing.
Period Title: Overall Study
STARTED	107	99
COMPLETED	78	71
NOT COMPLETED	29	28

Baseline Characteristics

Arm/Group Title	dermaPACE Application + Standard of Care	Non-energized (Inactive) Application + Standard of Care	Total
Arm/Group Description	dermaPACE: dermaPACE + Standard of care wound dressing.	Sham: Sham treatment (non-energized, inactive device) + Standard of care wound dressing.	Total of all reporting groups
Overall Participants	107	99	206
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.4 (10.4)	56.2 (9.4)	58.3 (9.9)
Sex: Female, Male (Count of Participants)
Female	24 22.4%	16 16.2%	40 19.4%
Male	83 77.6%	83 83.8%	166 80.6%
Region of Enrollment (participants) [Number]
United States	103 96.3%	94 94.9%	197 95.6%
Germany	2 1.9%	3 3%	5 2.4%
United Kingdom	2 1.9%	2 2%	4 1.9%

Outcome Measures

1. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	dermaPACE Application + Standard of Care	Non-energized (Inactive) Application + Standard of Care
Arm/Group Description	dermaPACE application + standard of care dermaPACE: dermaPACE + Standard of care wound dressing.	Non-energized (inactive) application + standard of care Sham: Sham treatment + Standard of care wound dressing.
Measure Participants	107	99
Number (95% Confidence Interval) [participants]	22 20.6%	15 15.2%

2. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	dermaPACE Application + Standard of Care		Non-energized (Inactive) Application + Standard of Care
Arm/Group Description	dermaPACE application + standard of care dermaPACE: dermaPACE + Standard of care wound dressing.		Non-energized (inactive) application + standard of care Sham: Sham treatment + Standard of care wound dressing.
All Cause Mortality
	dermaPACE Application + Standard of Care		Non-energized (Inactive) Application + Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	dermaPACE Application + Standard of Care		Non-energized (Inactive) Application + Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/107 (31.8%)		37/99 (37.4%)
Cardiac disorders
MI and cardiac failure	6/107 (5.6%)		6/99 (6.1%)
Gastrointestinal disorders
GI Haemmorhage	2/107 (1.9%)		2/99 (2%)
General disorders
application site disorders	3/107 (2.8%)		1/99 (1%)
Infections and infestations
Application site infections	16/107 (15%)		27/99 (27.3%)
Injury, poisoning and procedural complications
Fall, complication from other procedure	1/107 (0.9%)		1/99 (1%)
Investigations
bacterial test positive	0/107 (0%)		1/99 (1%)
Metabolism and nutrition disorders
dehydration and other disease related problems	4/107 (3.7%)		1/99 (1%)
Musculoskeletal and connective tissue disorders
Arthritis and joint pain	2/107 (1.9%)		0/99 (0%)
Nervous system disorders
ischemic attack, syncope	2/107 (1.9%)		2/99 (2%)
Renal and urinary disorders
renal failure	2/107 (1.9%)		2/99 (2%)
Respiratory, thoracic and mediastinal disorders
respiratory failure	1/107 (0.9%)		1/99 (1%)
Skin and subcutaneous tissue disorders
skin necrosis	0/107 (0%)		1/99 (1%)
Vascular disorders
diabetic vascular disorder	1/107 (0.9%)		1/99 (1%)
Other (Not Including Serious) Adverse Events
	dermaPACE Application + Standard of Care		Non-energized (Inactive) Application + Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	54/107 (50.5%)		42/99 (42.4%)
Blood and lymphatic system disorders
blood deficiencies	3/107 (2.8%)		3/99 (3%)
Cardiac disorders
cardiac disorders	4/107 (3.7%)		1/99 (1%)
Ear and labyrinth disorders
hearing disorders	4/107 (3.7%)		1/99 (1%)
Eye disorders
eye conditions	2/107 (1.9%)		5/99 (5.1%)
Gastrointestinal disorders
nausea, stomach discomfort, bowel conditions	12/107 (11.2%)		16/99 (16.2%)
General disorders
target site pain, irritation, illnesses	24/107 (22.4%)		31/99 (31.3%)
Immune system disorders
allergies	2/107 (1.9%)		1/99 (1%)
Infections and infestations
infections	39/107 (36.4%)		21/99 (21.2%)
Injury, poisoning and procedural complications
non-ulcer injuries	23/107 (21.5%)		16/99 (16.2%)
Investigations
blood tests, weight increase	11/107 (10.3%)		16/99 (16.2%)
Metabolism and nutrition disorders
anorexia, dehydration, diabetes related conditions	28/107 (26.2%)		20/99 (20.2%)
Musculoskeletal and connective tissue disorders
joint and muscle pain	16/107 (15%)		10/99 (10.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
skin papilloma	0/107 (0%)		1/99 (1%)
Nervous system disorders
headache, syncope, dizziness, ischemic attack	13/107 (12.1%)		9/99 (9.1%)
Psychiatric disorders
anxiety, depression	5/107 (4.7%)		3/99 (3%)
Renal and urinary disorders
renal failure, incontinence	3/107 (2.8%)		6/99 (6.1%)
Reproductive system and breast disorders
prostatic hypoplasia, vulvovaginal burning	2/107 (1.9%)		2/99 (2%)
Respiratory, thoracic and mediastinal disorders
coughing, congestion	8/107 (7.5%)		7/99 (7.1%)
Skin and subcutaneous tissue disorders
blisters, dermatitis, non-ulcer skin conditions	18/107 (16.8%)		15/99 (15.2%)
Vascular disorders
arterial stenosis, DVT, hypertension	7/107 (6.5%)		6/99 (6.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.