Trial Outcomes & Findings for Ultrasound Assisted Wound Debridement (UAW) Versus Standard Wound Treatment in Complicated Diabetic Foot Ulcers (DFU) (NCT NCT04633642)

Last Updated: 2021-07-14

Results Overview

Sections of tissue were immunohistochemically-stained with the CD31 marker. Light microscopy was used to count the number of microvessels/endothelial cells in a standardized grid, with the results expressed as microvessel density (Leica DMD 800 morphometric system). Microvessel density was scored according to the following scale: 0 (absent), 1 (low, at least one microvessel), 2 (moderate) and 3 (more than two micro vessels). Higher scores mean a better outcome

Recruitment status

COMPLETED

Study phase

Target enrollment

51 participants

Primary outcome timeframe

At week zero and week 6

Results posted on

2021-07-14

Participant Flow

An open-label randomized and controlled parallel clinical trial was performed involving outpatients with complicated Diabetic Foot Ulcer that were admitted to specialized diabetic foot unit between November 2017 to December 2019.

51 patients met inclusion criteria and were were randomized to treatment

Participant milestones

Participant milestones
Measure	Ultrasound Group (UAW Group) For most wounds in the UAW group, a two-minute treatment with 40% intensity was performed by holding the sonotrode in contact mode, holding it perpendicular to the wound bed and moving it across in an up-and-down pattern. Every week during 6 weeks	Surgical Group Surgical debridement involved removal of all necrotic and devitalized tissue that was incompatible with healing, as well as surrounding callus. Every week during 6 weeks
Overall Study STARTED	27	24
Overall Study COMPLETED	26	22
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Ultrasound Group (UAW Group) For most wounds in the UAW group, a two-minute treatment with 40% intensity was performed by holding the sonotrode in contact mode, holding it perpendicular to the wound bed and moving it across in an up-and-down pattern. Every week during 6 weeks	Surgical Group Surgical debridement involved removal of all necrotic and devitalized tissue that was incompatible with healing, as well as surrounding callus. Every week during 6 weeks
Overall Study Chronic renal disease, critical limb ischemia and heart attack	1	2

Baseline Characteristics

Ultrasound Assisted Wound Debridement (UAW) Versus Standard Wound Treatment in Complicated Diabetic Foot Ulcers (DFU)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ultrasound Group (UAW Group) n=27 Participants UAW debridement was performed using an UAW SONOCA 185 device (Söring GmbH, Germany). The UAW device generates an ultrasound low frequency of 25kHz and is equipped with three UAW instruments with different sonotrode shapes. The choice of sonotrode depends on wound depth, which ranges from superficial to deep. The UAW instrument piezoelectrically transforms the electrical energy delivered from the UAW device into mechanical oscillations in the sonotrode tip. For most wounds in the UAW group, a two-minute treatment with 40% intensity was performed by holding the sonotrode in contact mode, holding it perpendicular to the wound bed and moving it across in an up-and-down pattern. Ultrasound group: For most wounds in the UAW group, a two-minute treatment with 40% intensity was performed by holding the sonotrode in contact mode, holding it perpendicular to the wound bed and moving it across in an up-and-down pattern. For wounds measuring \>15cm2, the debridement procedure was increased to three minutes. In addition to UAW debridement, a scalpel was used for careful tissue removal, but only if periwound skin exhibited calluses and maceration.	Surgical Group n=24 Participants All debridement procedures were performed by the same surgeon (J.L.M.), who is specialist in diabetic foot surgery with more than 20 years of experience. Surgical debridement involved removal of all necrotic and devitalized tissue that was incompatible with healing, as well as surrounding callus. Ultrasound group: For most wounds in the UAW group, a two-minute treatment with 40% intensity was performed by holding the sonotrode in contact mode, holding it perpendicular to the wound bed and moving it across in an up-and-down pattern. For wounds measuring \>15cm2, the debridement procedure was increased to three minutes. In addition to UAW debridement, a scalpel was used for careful tissue removal, but only if periwound skin exhibited calluses and maceration.	Total n=51 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	24 Participants n=5 Participants	22 Participants n=7 Participants	46 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Age, Continuous	64.1 years STANDARD_DEVIATION 12.4 • n=5 Participants	58 years STANDARD_DEVIATION 5.4 • n=7 Participants	61.1 years STANDARD_DEVIATION 8.9 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	24 Participants n=7 Participants	48 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	27 Participants n=5 Participants	24 Participants n=7 Participants	51 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Spain	27 participants n=5 Participants	24 participants n=7 Participants	51 participants n=5 Participants
Type Diabetes Mellitus Type 1	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants
Type Diabetes Mellitus Type 2	22 Participants n=5 Participants	24 Participants n=7 Participants	46 Participants n=5 Participants
Duration of Diabetes	22 years STANDARD_DEVIATION 12.9 • n=5 Participants	10.3 years STANDARD_DEVIATION 5.0 • n=7 Participants	16.15 years STANDARD_DEVIATION 8.95 • n=5 Participants
Glycated hemoglobin	57 mmol/L STANDARD_DEVIATION 9.9 • n=5 Participants	51 mmol/L STANDARD_DEVIATION 4.5 • n=7 Participants	54 mmol/L STANDARD_DEVIATION 9.4 • n=5 Participants
Texas Classification IB	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Texas Classification II B	3 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants
Texas Classification ID	12 Participants n=5 Participants	8 Participants n=7 Participants	20 Participants n=5 Participants
Texas Classification IID	8 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: At week zero and week 6

Outcome measures

Outcome measures
Measure	Ultrasound Group (UAW Group) n=27 Participants UAW debridement was performed using an UAW SONOCA 185 device (Söring GmbH, Germany). The UAW device generates an ultrasound low frequency of 25kHz and is equipped with three UAW instruments with different sonotrode shapes. The choice of sonotrode depends on wound depth, which ranges from superficial to deep. The UAW instrument piezoelectrically transforms the electrical energy delivered from the UAW device into mechanical oscillations in the sonotrode tip. For most wounds in the UAW group, a two-minute treatment with 40% intensity was performed by holding the sonotrode in contact mode, holding it perpendicular to the wound bed and moving it across in an up-and-down pattern. Ultrasound group: For most wounds in the UAW group, a two-minute treatment with 40% intensity was performed by holding the sonotrode in contact mode, holding it perpendicular to the wound bed and moving it across in an up-and-down pattern. For wounds measuring \>15cm2, the debridement procedure was increased to three minutes. In addition to UAW debridement, a scalpel was used for careful tissue removal, but only if periwound skin exhibited calluses and maceration.	Surgical Group n=24 Participants All debridement procedures were performed by the same surgeon (J.L.M.), who is specialist in diabetic foot surgery with more than 20 years of experience. Surgical debridement involved removal of all necrotic and devitalized tissue that was incompatible with healing, as well as surrounding callus. Ultrasound group: For most wounds in the UAW group, a two-minute treatment with 40% intensity was performed by holding the sonotrode in contact mode, holding it perpendicular to the wound bed and moving it across in an up-and-down pattern. For wounds measuring \>15cm2, the debridement procedure was increased to three minutes. In addition to UAW debridement, a scalpel was used for careful tissue removal, but only if periwound skin exhibited calluses and maceration.
Change From Baseline Neo-angiogenesis (Microvessel Density) at 6 Weeks	2.82 score on a scale Standard Deviation 0.52	1.77 score on a scale Standard Deviation 1.30

PRIMARY outcome

Timeframe: At week zero and week 6

Massons's trichome staining was used to differentiate collagen content from other components, such as muscle fibrin and erythrocytes, in tissue samples. Collagen content was scored according to the following scale: 0 (absent), 1 (mild), 2 (moderate) and 3 (severe). Higher scores mean a better outcome.

Outcome measures

Outcome measures
Measure	Ultrasound Group (UAW Group) n=27 Participants UAW debridement was performed using an UAW SONOCA 185 device (Söring GmbH, Germany). The UAW device generates an ultrasound low frequency of 25kHz and is equipped with three UAW instruments with different sonotrode shapes. The choice of sonotrode depends on wound depth, which ranges from superficial to deep. The UAW instrument piezoelectrically transforms the electrical energy delivered from the UAW device into mechanical oscillations in the sonotrode tip. For most wounds in the UAW group, a two-minute treatment with 40% intensity was performed by holding the sonotrode in contact mode, holding it perpendicular to the wound bed and moving it across in an up-and-down pattern. Ultrasound group: For most wounds in the UAW group, a two-minute treatment with 40% intensity was performed by holding the sonotrode in contact mode, holding it perpendicular to the wound bed and moving it across in an up-and-down pattern. For wounds measuring \>15cm2, the debridement procedure was increased to three minutes. In addition to UAW debridement, a scalpel was used for careful tissue removal, but only if periwound skin exhibited calluses and maceration.	Surgical Group n=24 Participants All debridement procedures were performed by the same surgeon (J.L.M.), who is specialist in diabetic foot surgery with more than 20 years of experience. Surgical debridement involved removal of all necrotic and devitalized tissue that was incompatible with healing, as well as surrounding callus. Ultrasound group: For most wounds in the UAW group, a two-minute treatment with 40% intensity was performed by holding the sonotrode in contact mode, holding it perpendicular to the wound bed and moving it across in an up-and-down pattern. For wounds measuring \>15cm2, the debridement procedure was increased to three minutes. In addition to UAW debridement, a scalpel was used for careful tissue removal, but only if periwound skin exhibited calluses and maceration.
Change From Baseline Collagen Formation (Collagen Content ) at 6 Weeks	2.81 score on a scale Standard Deviation 0.48	1.20 score on a scale Standard Deviation 0.26

PRIMARY outcome

Timeframe: At week zero and week 6

Actin staining was used to evaluate the presence of myofibroblasts involved in wound healing. These cells increase in number during wound healing. The number of stained cells was semi-quantitatively analyzed using a 0 - 3 scaling score (0= no myofibroblasts, 1= myofibroblasts in low quantity, 2= myofibroblasts in moderate quantity, 3= myofibroblasts in high quantity)

Outcome measures

Outcome measures
Measure	Ultrasound Group (UAW Group) n=27 Participants UAW debridement was performed using an UAW SONOCA 185 device (Söring GmbH, Germany). The UAW device generates an ultrasound low frequency of 25kHz and is equipped with three UAW instruments with different sonotrode shapes. The choice of sonotrode depends on wound depth, which ranges from superficial to deep. The UAW instrument piezoelectrically transforms the electrical energy delivered from the UAW device into mechanical oscillations in the sonotrode tip. For most wounds in the UAW group, a two-minute treatment with 40% intensity was performed by holding the sonotrode in contact mode, holding it perpendicular to the wound bed and moving it across in an up-and-down pattern. Ultrasound group: For most wounds in the UAW group, a two-minute treatment with 40% intensity was performed by holding the sonotrode in contact mode, holding it perpendicular to the wound bed and moving it across in an up-and-down pattern. For wounds measuring \>15cm2, the debridement procedure was increased to three minutes. In addition to UAW debridement, a scalpel was used for careful tissue removal, but only if periwound skin exhibited calluses and maceration.	Surgical Group n=24 Participants All debridement procedures were performed by the same surgeon (J.L.M.), who is specialist in diabetic foot surgery with more than 20 years of experience. Surgical debridement involved removal of all necrotic and devitalized tissue that was incompatible with healing, as well as surrounding callus. Ultrasound group: For most wounds in the UAW group, a two-minute treatment with 40% intensity was performed by holding the sonotrode in contact mode, holding it perpendicular to the wound bed and moving it across in an up-and-down pattern. For wounds measuring \>15cm2, the debridement procedure was increased to three minutes. In addition to UAW debridement, a scalpel was used for careful tissue removal, but only if periwound skin exhibited calluses and maceration.
Change From Baseline Myofibroblasts Formation (Myofibroblasts Content) at 6 Weeks	2.56 score on a scale Standard Error 0.89	2.00 score on a scale Standard Error 0.10

SECONDARY outcome

Timeframe: At week zero and week 6

Tissue samples were weighed and mechanically homogenised in 0.5ml volumes of sterile phosphate buffered saline (PBS, Sigma Aldrich, St Louis, MO). Homogenates were diluted and plated onto Columbia agar (BD, Sparks, MD), Columbia agar supplemented with colistin and nalidixic acid (BD), MacConkey agar (BD), and Sabouraud dextrose agar (BD) using a spiral plater workstation (Don Whitley Scientific, Shipley, UK).The limit of detection was 10 colony-forming units (CFU). Results were expressed as CFU per gram of tissue (CFU/g). Isolated microorganisms were identified by standard criteria and the BBL Crystal identification system (BD). Susceptibility testing of Staphylococcus aureus isolates for oxacillin was performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines, using a 30g cefoxitin disc and Mueller-Hinton agar .

Outcome measures

Outcome measures
Measure	Ultrasound Group (UAW Group) n=27 Participants UAW debridement was performed using an UAW SONOCA 185 device (Söring GmbH, Germany). The UAW device generates an ultrasound low frequency of 25kHz and is equipped with three UAW instruments with different sonotrode shapes. The choice of sonotrode depends on wound depth, which ranges from superficial to deep. The UAW instrument piezoelectrically transforms the electrical energy delivered from the UAW device into mechanical oscillations in the sonotrode tip. For most wounds in the UAW group, a two-minute treatment with 40% intensity was performed by holding the sonotrode in contact mode, holding it perpendicular to the wound bed and moving it across in an up-and-down pattern. Ultrasound group: For most wounds in the UAW group, a two-minute treatment with 40% intensity was performed by holding the sonotrode in contact mode, holding it perpendicular to the wound bed and moving it across in an up-and-down pattern. For wounds measuring \>15cm2, the debridement procedure was increased to three minutes. In addition to UAW debridement, a scalpel was used for careful tissue removal, but only if periwound skin exhibited calluses and maceration.	Surgical Group n=24 Participants All debridement procedures were performed by the same surgeon (J.L.M.), who is specialist in diabetic foot surgery with more than 20 years of experience. Surgical debridement involved removal of all necrotic and devitalized tissue that was incompatible with healing, as well as surrounding callus. Ultrasound group: For most wounds in the UAW group, a two-minute treatment with 40% intensity was performed by holding the sonotrode in contact mode, holding it perpendicular to the wound bed and moving it across in an up-and-down pattern. For wounds measuring \>15cm2, the debridement procedure was increased to three minutes. In addition to UAW debridement, a scalpel was used for careful tissue removal, but only if periwound skin exhibited calluses and maceration.
Comparison of Quantitative Microbiological Analysis (Bacterial Counts Expressed Colony-forming Units Per Gram of Tissue) (CFU/g)	2.11 Log10 CFU/g Standard Deviation 0.8	4.39 Log10 CFU/g Standard Deviation 1.24

SECONDARY outcome

Timeframe: Six weeks

Wound bed tissue was evaluated for presence, quality, and consistency of granulation tissue using a validated wound scoring system, with scores ranging between a minimum of zero points and maximum of seven points. Higher scores mean a better outcome.

Outcome measures

Outcome measures
Measure	Ultrasound Group (UAW Group) n=27 Participants UAW debridement was performed using an UAW SONOCA 185 device (Söring GmbH, Germany). The UAW device generates an ultrasound low frequency of 25kHz and is equipped with three UAW instruments with different sonotrode shapes. The choice of sonotrode depends on wound depth, which ranges from superficial to deep. The UAW instrument piezoelectrically transforms the electrical energy delivered from the UAW device into mechanical oscillations in the sonotrode tip. For most wounds in the UAW group, a two-minute treatment with 40% intensity was performed by holding the sonotrode in contact mode, holding it perpendicular to the wound bed and moving it across in an up-and-down pattern. Ultrasound group: For most wounds in the UAW group, a two-minute treatment with 40% intensity was performed by holding the sonotrode in contact mode, holding it perpendicular to the wound bed and moving it across in an up-and-down pattern. For wounds measuring \>15cm2, the debridement procedure was increased to three minutes. In addition to UAW debridement, a scalpel was used for careful tissue removal, but only if periwound skin exhibited calluses and maceration.	Surgical Group n=24 Participants All debridement procedures were performed by the same surgeon (J.L.M.), who is specialist in diabetic foot surgery with more than 20 years of experience. Surgical debridement involved removal of all necrotic and devitalized tissue that was incompatible with healing, as well as surrounding callus. Ultrasound group: For most wounds in the UAW group, a two-minute treatment with 40% intensity was performed by holding the sonotrode in contact mode, holding it perpendicular to the wound bed and moving it across in an up-and-down pattern. For wounds measuring \>15cm2, the debridement procedure was increased to three minutes. In addition to UAW debridement, a scalpel was used for careful tissue removal, but only if periwound skin exhibited calluses and maceration.
Wound Score at 6 Weeks	5.4 score on a scale Standard Deviation 1.5	5.6 score on a scale Standard Deviation 0.7

SECONDARY outcome

Timeframe: 6 weeks

A planimetric measurements of wound size were conducted using Visitrak (Smith \& Nephew, Hull, UK), with the area of the lesion determined with an approximation of ±5mm2

Outcome measures

Outcome measures
Measure	Ultrasound Group (UAW Group) n=27 Participants UAW debridement was performed using an UAW SONOCA 185 device (Söring GmbH, Germany). The UAW device generates an ultrasound low frequency of 25kHz and is equipped with three UAW instruments with different sonotrode shapes. The choice of sonotrode depends on wound depth, which ranges from superficial to deep. The UAW instrument piezoelectrically transforms the electrical energy delivered from the UAW device into mechanical oscillations in the sonotrode tip. For most wounds in the UAW group, a two-minute treatment with 40% intensity was performed by holding the sonotrode in contact mode, holding it perpendicular to the wound bed and moving it across in an up-and-down pattern. Ultrasound group: For most wounds in the UAW group, a two-minute treatment with 40% intensity was performed by holding the sonotrode in contact mode, holding it perpendicular to the wound bed and moving it across in an up-and-down pattern. For wounds measuring \>15cm2, the debridement procedure was increased to three minutes. In addition to UAW debridement, a scalpel was used for careful tissue removal, but only if periwound skin exhibited calluses and maceration.	Surgical Group n=24 Participants All debridement procedures were performed by the same surgeon (J.L.M.), who is specialist in diabetic foot surgery with more than 20 years of experience. Surgical debridement involved removal of all necrotic and devitalized tissue that was incompatible with healing, as well as surrounding callus. Ultrasound group: For most wounds in the UAW group, a two-minute treatment with 40% intensity was performed by holding the sonotrode in contact mode, holding it perpendicular to the wound bed and moving it across in an up-and-down pattern. For wounds measuring \>15cm2, the debridement procedure was increased to three minutes. In addition to UAW debridement, a scalpel was used for careful tissue removal, but only if periwound skin exhibited calluses and maceration.
Wound Size	1.0 Centimeter square Standard Deviation 1.22	0.88 Centimeter square Standard Deviation 1.04

Adverse Events

Ultrasound Group (UAW Group)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Surgical Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Francisco Javier Álvaro Afonso

Diabetic Foot Unit, Clínica Universitaria de Podología, Facultad de Enfermería, Fisioterapia y Podología, Universidad Complutense de Madrid, 28040 Madrid, Spain

Phone: 913-941-502

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place