Inforatio Technique to Promote Wound Healing of Diabetic Foot Ulcers

NCT05189470 | Completed DMC

• 3 other identifiers: EMN-2021-08362SJ-904REG-116-2021
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 4

Brief Summary

This randomized clinical trial will examine the effect of inforatio technique on healing of diabetic foot ulcers (DFUs). Inforatio technique is a novel procedure developed by the research group. The definition of inforatio technique is application of small cuts in wound beds with punch biopsy tools without involving surrounding epithelia. The aim is to initiate an acute inflammatory response that will promote healing of the ulcers.

Conditions

Diabetes; Foot Ulcer; Diabetic Foot; Diabetes Mellitus; Diabetic Foot Ulcer; Diabetes Complications

Keywords

Diabetic Foot Ulcer; Wound treatment; Inforatio technique

Outcome Measures

Primary Outcomes (1)

• Complete healing

  Healing is defined as complete epithelialization without any discharge from the site of the index ulcer. The primary outcome is the proportion of ulcers in each allocation group where healing is observed based on blinded assessment of digital images from the participants' last trial visit. The assessment of healing on digital images will be performed separately by two blinded assessors. Digital images where disagreement occurs are discussed between the assessors until agreement is reached. Any inconsistencies between the blinded assessment of healing on images and unblinded clinical assessment at trial visits will be reported. In case of death and amputation the primary outcome is registered as non-healing.

  20 weeks

Secondary Outcomes (2)

• Change in EQ-5D-5L visual analog scale (EQ VAS) score from baseline to end of follow-up

  20 weeks

• Change in Wound-QoL global score from baseline to end of follow-up

  20 weeks

Other Outcomes (6)

• Inforatio related adverse events

  20 weeks

• Ulcer-related adverse events

  20 weeks

• Patient-reported adverse events

  20 weeks

Study Arms (2)

Control group

OTHER

These participants will receive the usual care of the respective outpatient clinics.

Other: Usual care of the respective outpatient clinics

Intervention group

EXPERIMENTAL

Participants that are randomized to the intervention group will receive both inforatio technique and usual care. Inforatio technique will be applied at baseline, 3, 6, 9 and 12 week- follow-up as long as the ulcers have a diameter of minimum four mms and have not developed infection, necrosis, positive probe-to-bone test, exposure of joint or tendon; or underlying osteomyelitis. In addition, inforatio technique will not be applied on ulcers that are covered by scab if the wound care staff assess that the scab should not be removed from the ulcer.

Procedure: Inforatio technique; Other: Usual care of the respective outpatient clinics

Interventions

Inforatio technique PROCEDURE

Inforatio technique is a novel minimal invasive procedure where small cuts are made on wound beds with punch biopsy tools near the wound edges but without involving wound edge epithelia. Inforatio technique is applied after the wound has been surgically debrided for slough and devitalized tissue.

Intervention group

Usual care of the respective outpatient clinics OTHER

Usual care of the DFUs includes local wound care and offloading treatment.

Control group; Intervention group

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• Diabetes mellitus
• Non-surgical ulcer located distal to the malleoli
• Wound diameter \>4 millimeters
• Patient-reported wound duration ≥ 6 weeks
• Only one ulcer will be included from each participant. If a patient has more than one eligible ulcer, the largest ulcer is included. In case of equally sized ulcers, the ulcer with the most recent onset is included.

You may not qualify if:

• Dementia or other reasons that cause inability to give informed consent
• Malignant disease
• Current treatment with systemic immunosuppressive drugs.
• Diagnosed with or awaiting evaluation of suspected acute phase Charcot arthropathy or osteomyelitis
• Non-palpable pulse in both arteria dorsalis pedis and arteria tibialis posterior accompanied by systolic toe pressure \<30 mmHg in the index foot.
• Amputation at midfoot level or proximal to midfoot level
• Revascularization procedure awaits or has been undertaken within the last 8 weeks or the patient awaits a vascular surgeons' decision on revascularization
• Gangrene
• Infection of the ulcer defined according to IWGDF/IDSA (International Working Group on the Diabetic Foot/ Infectious Diseases Society of America system) classification as presence of at least 2 of the following; 1) local swelling or induration; 2) erythema \>0.5 to ≤2 cm around the ulcer; 3) local tenderness or pain; 4) local warmth; or 5) purulent discharge. Current antibiotic treatment due to infection of the index ulcer will also be considered as an ongoing infection regardless of presence of clinical signs of infection.
• Positive probe-to-bone test
• Exposed joint or tendon
• The soft tissue layer covering bone or joint is evaluated to be too thin to allow for inforatio technique anywhere in the wound bed.
• Interdigital ulcer location

Sponsors & Collaborators

• Zealand University Hospital: lead
• Steno Diabetes Center Sjaelland: collaborator

Study Sites (4)

Herlev University Hospital, Department of Orthopaedic Surgery

Herlev, 2730, Denmark

Location

Zealand University Hospital, Department of Orthopaedic Surgery

Køge, 4600, Denmark

Location

Nykoebing Falster Hospital

Nykøbing Falster, 4800, Denmark

Location

Slagelse Hospital, Department of Orthopaedic Surgery

Slagelse, 4200, Denmark

Location

Related Publications (10)

• Andrews KL, Houdek MT, Kiemele LJ. Wound management of chronic diabetic foot ulcers: from the basics to regenerative medicine. Prosthet Orthot Int. 2015 Feb;39(1):29-39. doi: 10.1177/0309364614534296.

  PMID: 25614499 BACKGROUND

• Karri VV, Kuppusamy G, Talluri SV, Yamjala K, Mannemala SS, Malayandi R. Current and emerging therapies in the management of diabetic foot ulcers. Curr Med Res Opin. 2016;32(3):519-42. doi: 10.1185/03007995.2015.1128888. Epub 2016 Jan 12.

  PMID: 26643047 BACKGROUND

• Zimny S, Pfohl M. Healing times and prediction of wound healing in neuropathic diabetic foot ulcers: a prospective study. Exp Clin Endocrinol Diabetes. 2005 Feb;113(2):90-3. doi: 10.1055/s-2004-830537.

  PMID: 15772900 BACKGROUND

• Greer N, Foman NA, MacDonald R, Dorrian J, Fitzgerald P, Rutks I, Wilt TJ. Advanced wound care therapies for nonhealing diabetic, venous, and arterial ulcers: a systematic review. Ann Intern Med. 2013 Oct 15;159(8):532-42. doi: 10.7326/0003-4819-159-8-201310150-00006.

  PMID: 24126647 BACKGROUND

• Devlin N, Parkin D, Janssen B. Methods for Analysing and Reporting EQ-5D Data [Internet]. Cham (CH): Springer; 2020. No abstract available. Available from http://www.ncbi.nlm.nih.gov/books/NBK565678/

  PMID: 33347096 BACKGROUND

• Jakobsen JC, Gluud C, Wetterslev J, Winkel P. When and how should multiple imputation be used for handling missing data in randomised clinical trials - a practical guide with flowcharts. BMC Med Res Methodol. 2017 Dec 6;17(1):162. doi: 10.1186/s12874-017-0442-1.

  PMID: 29207961 BACKGROUND

• Margolis DJ, Kantor J, Berlin JA. Healing of diabetic neuropathic foot ulcers receiving standard treatment. A meta-analysis. Diabetes Care. 1999 May;22(5):692-5. doi: 10.2337/diacare.22.5.692.

  PMID: 10332667 BACKGROUND

• Moeini S, Gottlieb H, Jorgensen TS, Larsen MRB, Brorson S. Treatment of Diabetic Foot Ulcers With Inforatio Technique to Promote Wound Healing: A Feasibility Trial. Int J Low Extrem Wounds. 2023 Jun;22(2):241-250. doi: 10.1177/15347346211002364. Epub 2021 Apr 28.

  PMID: 33909504 BACKGROUND

• Monteiro-Soares M, Russell D, Boyko EJ, Jeffcoate W, Mills JL, Morbach S, Game F; International Working Group on the Diabetic Foot (IWGDF). Guidelines on the classification of diabetic foot ulcers (IWGDF 2019). Diabetes Metab Res Rev. 2020 Mar;36 Suppl 1:e3273. doi: 10.1002/dmrr.3273.

  PMID: 32176445 BACKGROUND

• Moeini S, Gottlieb H, Jorgensen TS, Aagaard TV, Korno MR, Larsen MRB, Brorson S. Inforatio technique to promote wound healing of diabetic foot ulcers: study protocol for a parallel-group, evaluator-blinded, randomised clinical trial. BMJ Open. 2022 Sep 19;12(9):e062344. doi: 10.1136/bmjopen-2022-062344.

  PMID: 36123051 DERIVED

Related Links

• Chadwick P, Edmonds M, Mccardle J, Armstrong D. International Best Practice Guidelines: Wound management in diabetic foot ulcers. Wounds International. Published 2013. Accessed November 26, 2020.
• EuroQol Research Foundation. EQ-5D-5L User Guide. Published 2019. Accessed December 16, 2020.
• Wound-QoL. Wound-QoL User Manual. User Manual for the questionnaire on quality of life with chronic wounds. Published 2020. Accessed January 20, 2021.
• FDA. What is a Serious Adverse Event? Published 2016. Accessed December 16, 2020.

MeSH Terms

Conditions

Diabetic Foot; Diabetes Mellitus; Foot Ulcer; Diabetes Complications

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine System Diseases; Diabetic Neuropathies; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Foot Diseases

Study Officials

• Sahar Moeini, MD

  Zealand University Hospital

  PRINCIPAL INVESTIGATOR

• Hans Gottlieb, MD PhD

  University of Copenhagen

  STUDY CHAIR

• Tue S Jørgensen, MD PhD

  Zealand University Hospital

  STUDY CHAIR

• Thomas V Aagaard, PT MsC

  Holbaek Hospital

  STUDY CHAIR

• Maj R Kornø, MD

  Nykoebing Falster Hospital

  STUDY CHAIR

• Malene RB Larsen, MD

  Zealand University Hospital

  STUDY CHAIR

• Stig Brorson, MD PhD DMsc

  Zealand University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Healing is assessed on digital ulcer images by assessors that are blinded to treatment allocation. The digital images will be blinded by the primary investigator before delivery to the assessors. Data analysts will also be blinded to treatment allocation. It is not possible to blind participants or the staff that perform wound care and clinical assessment of healing because inforatios are visible in the wound bed after application.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized clinical trial

Study Record Dates

• First Submitted: December 27, 2021
• First Posted: January 12, 2022
• Study Start: March 10, 2022
• Primary Completion: December 18, 2024
• Study Completion: August 14, 2025
• Last Updated: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

DK (4)