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

NCT04633642 | Completed Results DMC

• 1 other identifier: C.P. - C.I. 16/484-P
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 2

Brief Summary

The investigators aimed to elucidate the effects of UAW debridement on cellular proliferation and dermal repair in complicated diabetic foot ulcers as compared to diabetic foot ulcers receiving surgical/sharp wound debridement. A randomized controlled trial was performed involving outpatients with complicated diabetic foot ulcers that either received surgical debridement or UAW debridement every week during a six-week treatment period.

Conditions

Diabetic Foot Ulcer

Keywords

ultrasound assisted wound debridement; surgical debridement; cellular proliferation; microbiology; diabetic foot ulcers

Outcome Measures

Primary Outcomes (3)

• Change From Baseline Neo-angiogenesis (Microvessel Density) at 6 Weeks

  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

  At week zero and week 6

• Change From Baseline Collagen Formation (Collagen Content ) at 6 Weeks

  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.

  At week zero and week 6

• Change From Baseline Myofibroblasts Formation (Myofibroblasts Content) at 6 Weeks

  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)

  At week zero and week 6

Secondary Outcomes (3)

• Comparison of Quantitative Microbiological Analysis (Bacterial Counts Expressed Colony-forming Units Per Gram of Tissue) (CFU/g)

  At week zero and week 6

• Wound Score at 6 Weeks

  Six weeks

• Wound Size

  6 weeks

Study Arms (2)

Ultrasound Group (UAW group)

EXPERIMENTAL

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.

Procedure: Ultrasound group

Surgical group

ACTIVE COMPARATOR

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.

Procedure: Surgical group

Interventions

Ultrasound group PROCEDURE

Every week during a six-week treatment period

Ultrasound Group (UAW group)

Surgical group PROCEDURE

Every week during a six-week treatment period

Surgical group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients ≥18 years old
• Type 1 or type 2 diabetes with levels of HbA1c≤85.8 mmol/mol (10%) within 30 days of the beginning of the study
• Wound stages IB, IIB, ID, and IID according to the University of Texas Diabetic Wound Classification \[11\]
• Wound duration of 1-24 months
• Wound size between 1-30 cm2 after debridement
• Clinical picture of wounds showing mild or moderate infection, according to the criteria of the Infectious Disease Society of America Guidelines \[12\] and the European Wound Management Association (EWMA) \[13\]
• Ankle-brachial index (ABI) ≤0.9 and ankle systolic blood pressure (ASBP) ≥70mmHg, or toe systolic blood pressure (TSBP) ≥50mmHg, ABI\>0.9, TSBP ≥50mmHg and toe-brachial index (TBI) ≤0.7

You may not qualify if:

• Chronic renal disease or dialysis
• Non-treated osteomyelitis
• Necrotizing soft tissue infections
• Critical limb ischaemia patients with ABI≤0.5 and ASBP\<70mmHg or \<50mmHg
• Life expectancy \<6 months due to malignant DFU
• Pregnancy and lactation
• Patients diagnosed with hepatitis or human immunodeficiency virus (HIV)
• Patients showing local or systemic conditions that may impair tissue repair

Sponsors & Collaborators

• Universidad Complutense de Madrid: lead
• Francisco Javier Álvaro Afonso: collaborator
• David Sevillano Fernández: collaborator
• Yolanda García Álvarez: collaborator
• Irene Sanz Corbalan: collaborator
• Esther García Morales: collaborator

Study Sites (2)

Fancisco Javier Álvaro Afonso

Madrid, 28039, Spain

Location

José Luis Lázaro Martínez

Madrid, 28039, Spain

Location

Related Publications (26)

• Schaper NC, van Netten JJ, Apelqvist J, Bus SA, Hinchliffe RJ, Lipsky BA; IWGDF Editorial Board. Practical Guidelines on the prevention and management of diabetic foot disease (IWGDF 2019 update). Diabetes Metab Res Rev. 2020 Mar;36 Suppl 1:e3266. doi: 10.1002/dmrr.3266.

  PMID: 32176447 BACKGROUND

• Kim PJ, Steinberg JS. Wound care: biofilm and its impact on the latest treatment modalities for ulcerations of the diabetic foot. Semin Vasc Surg. 2012 Jun;25(2):70-4. doi: 10.1053/j.semvascsurg.2012.04.008.

  PMID: 22817855 BACKGROUND

• Kingsley A, Lewis T, White R. Debridement and wound biofilms. J Wound Care. 2011 Jun;20(6):286. No abstract available.

  PMID: 21739682 BACKGROUND

• Swanson T, Lazaro-Martinez JL, Braumann C, Kirchhoff JB, Gachter B, van Acker K. Ultrasonic-assisted wound debridement: report from a closed panel meeting. J Wound Care. 2020 Feb 2;29(2):128-135. doi: 10.12968/jowc.2020.29.2.128.

  PMID: 32058848 BACKGROUND

• Rayman G, Vas P, Dhatariya K, Driver V, Hartemann A, Londahl M, Piaggesi A, Apelqvist J, Attinger C, Game F; International Working Group on the Diabetic Foot (IWGDF). Guidelines on use of interventions to enhance healing of chronic foot ulcers in diabetes (IWGDF 2019 update). Diabetes Metab Res Rev. 2020 Mar;36 Suppl 1:e3283. doi: 10.1002/dmrr.3283.

  PMID: 32176450 BACKGROUND

• Lazaro-Martinez JL, Alvaro-Afonso FJ, Garcia-Alvarez Y, Molines-Barroso RJ, Garcia-Morales E, Sevillano-Fernandez D. Ultrasound-assisted debridement of neuroischaemic diabetic foot ulcers, clinical and microbiological effects: a case series. J Wound Care. 2018 May 2;27(5):278-286. doi: 10.12968/jowc.2018.27.5.278.

  PMID: 29738301 BACKGROUND

• Altland OD, Dalecki D, Suchkova VN, Francis CW. Low-intensity ultrasound increases endothelial cell nitric oxide synthase activity and nitric oxide synthesis. J Thromb Haemost. 2004 Apr;2(4):637-43. doi: 10.1111/j.1538-7836.2004.00655.x.

  PMID: 15102020 BACKGROUND

• Driver VR, Yao M. Discussion. Current status of the use of modalities in wound care: electrical stimulation and ultrasound therapy. Plast Reconstr Surg. 2011 Jan;127 Suppl 1:103S-104S. doi: 10.1097/PRS.0b013e3182050c35. No abstract available.

  PMID: 21200279 BACKGROUND

• Ennis WJ, Foremann P, Mozen N, Massey J, Conner-Kerr T, Meneses P. Ultrasound therapy for recalcitrant diabetic foot ulcers: results of a randomized, double-blind, controlled, multicenter study. Ostomy Wound Manage. 2005 Aug;51(8):24-39.

  PMID: 16234574 BACKGROUND

• Driver VR, Yao M, Miller CJ. Noncontact low-frequency ultrasound therapy in the treatment of chronic wounds: a meta-analysis. Wound Repair Regen. 2011 Jul-Aug;19(4):475-80. doi: 10.1111/j.1524-475X.2011.00701.x. Epub 2011 Jun 7.

  PMID: 21649783 BACKGROUND

• Armstrong DG, Lavery LA, Harkless LB. Validation of a diabetic wound classification system. The contribution of depth, infection, and ischemia to risk of amputation. Diabetes Care. 1998 May;21(5):855-9. doi: 10.2337/diacare.21.5.855.

  PMID: 9589255 BACKGROUND

• Lipsky BA, Berendt AR, Cornia PB, Pile JC, Peters EJ, Armstrong DG, Deery HG, Embil JM, Joseph WS, Karchmer AW, Pinzur MS, Senneville E; Infectious Diseases Society of America. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2012 Jun;54(12):e132-73. doi: 10.1093/cid/cis346.

  PMID: 22619242 BACKGROUND

• Boulton AJ, Armstrong DG, Albert SF, Frykberg RG, Hellman R, Kirkman MS, Lavery LA, Lemaster JW, Mills JL Sr, Mueller MJ, Sheehan P, Wukich DK; American Diabetes Association; American Association of Clinical Endocrinologists. Comprehensive foot examination and risk assessment: a report of the task force of the foot care interest group of the American Diabetes Association, with endorsement by the American Association of Clinical Endocrinologists. Diabetes Care. 2008 Aug;31(8):1679-85. doi: 10.2337/dc08-9021. No abstract available.

  PMID: 18663232 BACKGROUND

• Tan T, Shaw EJ, Siddiqui F, Kandaswamy P, Barry PW, Baker M; Guideline Development Group. Inpatient management of diabetic foot problems: summary of NICE guidance. BMJ. 2011 Mar 23;342:d1280. doi: 10.1136/bmj.d1280. No abstract available.

  PMID: 21430002 BACKGROUND

• Bus SA, Armstrong DG, Gooday C, Jarl G, Caravaggi C, Viswanathan V, Lazzarini PA; International Working Group on the Diabetic Foot (IWGDF). Guidelines on offloading foot ulcers in persons with diabetes (IWGDF 2019 update). Diabetes Metab Res Rev. 2020 Mar;36 Suppl 1:e3274. doi: 10.1002/dmrr.3274.

  PMID: 32176441 BACKGROUND

• Tardaguila-Garcia A, Lazaro-Martinez JL, Sanz-Corbalan I, Garcia-Alvarez Y, Alvaro-Afonso FJ, Garcia-Morales E. Correlation between Empirical Antibiotic Therapy and Bone Culture Results in Patients with Osteomyelitis. Adv Skin Wound Care. 2019 Jan;32(1):41-44. doi: 10.1097/01.ASW.0000542527.48815.1f.

  PMID: 30376455 BACKGROUND

• Wang D, Stockard CR, Harkins L, Lott P, Salih C, Yuan K, Buchsbaum D, Hashim A, Zayzafoon M, Hardy RW, Hameed O, Grizzle W, Siegal GP. Immunohistochemistry in the evaluation of neovascularization in tumor xenografts. Biotech Histochem. 2008 Jun;83(3-4):179-89. doi: 10.1080/10520290802451085.

  PMID: 18846440 BACKGROUND

• Achar RA, Silva TC, Achar E, Martines RB, Machado JL. Use of insulin-like growth factor in the healing of open wounds in diabetic and non-diabetic rats. Acta Cir Bras. 2014 Feb;29(2):125-31. doi: 10.1590/S0102-86502014000200009.

  PMID: 24604317 BACKGROUND

• Wollina U, Schmidt WD, Kronert C, Nelskamp C, Scheibe A, Fassler D. Some effects of a topical collagen-based matrix on the microcirculation and wound healing in patients with chronic venous leg ulcers: preliminary observations. Int J Low Extrem Wounds. 2005 Dec;4(4):214-24. doi: 10.1177/1534734605283001.

  PMID: 16286373 BACKGROUND

• World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013 Nov 27;310(20):2191-4. doi: 10.1001/jama.2013.281053. No abstract available.

  PMID: 24141714 BACKGROUND

• Maan ZN, Januszyk M, Rennert RC, Duscher D, Rodrigues M, Fujiwara T, Ho N, Whitmore A, Hu MS, Longaker MT, Gurtner GC. Noncontact, low-frequency ultrasound therapy enhances neovascularization and wound healing in diabetic mice. Plast Reconstr Surg. 2014 Sep;134(3):402e-411e. doi: 10.1097/PRS.0000000000000467.

  PMID: 25158717 BACKGROUND

• Roper JA, Williamson RC, Bally B, Cowell CAM, Brooks R, Stephens P, Harrison AJ, Bass MD. Ultrasonic Stimulation of Mouse Skin Reverses the Healing Delays in Diabetes and Aging by Activation of Rac1. J Invest Dermatol. 2015 Nov;135(11):2842-2851. doi: 10.1038/jid.2015.224. Epub 2015 Jun 16.

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• Butcher G, Pinnuck L. Wound bed preparation: ultrasonic-assisted debridement. Br J Nurs. 2013 Mar 28-Apr 10;22(6):S36, S38-43. doi: 10.12968/bjon.2013.22.Sup4.S36.

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• Michailidis L, Bergin SM, Haines TP, Williams CM. A Systematic Review to Compare the Effect of Low-frequency Ultrasonic Versus Nonsurgical Sharp Debridement on the Healing Rate of Chronic Diabetes-related Foot Ulcers. Ostomy Wound Manage. 2018 Sep;64(9):39-46.

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• Michailidis L, Bergin SM, Haines TP, Williams CM. Healing rates in diabetes-related foot ulcers using low frequency ultrasonic debridement versus non-surgical sharps debridement: a randomised controlled trial. BMC Res Notes. 2018 Oct 16;11(1):732. doi: 10.1186/s13104-018-3841-4.

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• Messa CA 4th, Chatman BC, Rhemtulla IA, Broach RB, Mauch JT, D'Angelantonio AM 3rd, Fischer JP. Ultrasonic debridement management of lower extremity wounds: retrospective analysis of clinical outcomes and cost. J Wound Care. 2019 May 1;28(Sup5):S30-S40. doi: 10.12968/jowc.2019.28.Sup5.S30.

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MeSH Terms

Conditions

Diabetic Foot; Hyperplasia

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Future trials may also evaluate efficiency or cost-effectiveness of both treatments

Results Point of Contact

• Title: Dr. Francisco Javier Álvaro Afonso
• Organization: Diabetic Foot Unit, Clínica Universitaria de Podología, Facultad de Enfermería, Fisioterapia y Podología, Universidad Complutense de Madrid, 28040 Madrid, Spain

alvaro@ucm.es

913-941-502

Study Officials

• Lázaro Martinez, Professor

  Universidad Complutense de Madrid

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.Dr

Model Details: A randomized and controlled parallel clinical trial

Study Record Dates

• First Submitted: October 30, 2020
• First Posted: November 18, 2020
• Study Start: November 1, 2017
• Primary Completion: November 1, 2018
• Study Completion: December 31, 2019
• Last Updated: July 14, 2021
• Results First Posted: July 14, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2)