Treatment of Diabetic Foot Ulcers With Inforatio Technique to Promote Wound Healing

NCT03985306 | Completed DMC

• 1 other identifier: REG-122-2018
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

This trial will examine the feasibility of conducting a definitive randomized clinical trial that tests whether inforatio technique will reduce time to healing of diabetic foot ulcers. Inforatio technique is a procedure where small punch biopsies are taken from the wound bed near the edge of the wound. With this technique, the investigators wish to initiate an acute inflammatory response that increases the generation of granulation tissue with subsequent healing by scar formation. Thus, the investigators hypothesize that inforatio technique will promote healing of diabetic foot ulcers. Based on clinical experience, the investigators have previously detected a reduction in time to healing as an unexpected effect when multiple punch biopsies are taken from the wound bed of diabetic foot ulcers. To the knowledge of the investigators, methods similar to the inforatio technique has not previously been studied.

Conditions

Diabetic Foot Ulcer; Diabetic Foot; Wound Heal; Ulcer Foot; Ulcer Healing

Keywords

Diabetic foot ulcer; Wound treatment; Inforatio technique; Diabetes; Foot ulcer; Outpatient clinic; Feasibility trial; Punch biopsy; Foot ulcer treatment

Outcome Measures

Primary Outcomes (23)

• Eligibility rates

  Descriptive statistics of number and rate of eligible patients during the period of recruitment

  The first 2 months of the trial (untill the last patient has been recruited)

• Refusal rates

  Descriptive statistics of number and rate of eligible patients that refuse trial participation.

  The first 2 months of the trial (untill the last patient has been recruited)

• Time from identification to inclusion

  Descriptive statistics of average time from eligible patients are identified to they are included in the trial (baseline trial visit)

  The first 2 months of the trial (untill the last patient has been recruited)

• Qualitative assessment of unexpected factors that must cause exclusion

  Qualitatively assessed by the primary investigator

  10 months

• Rate of unexpected exclusion

  Descriptive statistics of number and rate of patients that are excluded due to reasons not already covered by the trial definition of exclusion criteria.

  10 months

• Retention rates

  To investigate protocol adherence, the number and rate of participants that adhere to follow-up will be reported.

  10 months

• Number of missed trial follow-up visits

  To investigate protocol adherence, the number of missed trial visits will be reported for each participant.

  10 months

• Drop-out rates

  To investigate protocol adherence, the number and rate of participants that choose to drop out during follow-up will be reported.

  10 months

• Rate of eligible patients that accept participation

  A quantitative investigation of patient acceptability.

  At baseline, each follow-up visit and when patients drop out.

• Qualitative assessment of patient acceptability

  Assessed by interviews with participants.

  10 months

• Observed harms and unexpected effects

  Observed harms and unexpected effects observed by the investigators and staff will be reported.

  10 months

• Patient-reported potential side effects

  A qualitatively assessment of harms and unexpected effects by interviewing participants about potential side effects that they experience.

  10 months

• Qualitative assessment of logistics issues regarding outpatient clinic visits

  The investigators qualitatively assesses logistic circumstances that may be optimized.The assessment includes whether dates of follow-up visits fit the routines at the outpatient clinics.

  10 months

• Time to healing of punch biopsy scars

  The time to healing will be reported to estimate if and when observer blinding may be possible.

  10 months

• Qualitative assessment of the method of wound assessment.

  The investigators assess complications related to the method wound bed area and the depth. The aim is to optimize wound assessment for the future definitive trial.

  10 months

• Qualitative assessment of the extent of qualitative patient measures

  The investigators assess whether the qualitative patient measures are either too extensive or insufficient. Thus, estimating necessary changes to make the qualitative measurements feasible to include in the future definitive trial.

  10 months

• Qualitative assessment of the feasibility of culturing 3 biopsies from each round of inforatio technique applications for a future definitive trial.

  The investigators assess whether the included centers have the capacity to culture three biopsies two times from each patient.

  10 months

• Rates of wound treatments at trial visits that deviate from the trial standard treatment definition

  Standard treatments received by each patient at the follow-up visits are recorded and it is assessed whether the standard care received corresponds to the definition of the trial standard treatment.

  10 months

• Qualitative assessment of wound care treatments received between trial visits and the deviations from the trial definition of standard treatment.

  The investigators assess the heterogeneity of treatment during follow-up by recording the number of hospital visits between the trial follow-up visits and the treatments and assessments received at these hospital visits.

  10 months

• Time to healing of the foot ulcers

  The investigators will report mean and variance of time to healing

  10 months

• Patient-reported experience of trial participation and the inforatio technique

  The investigators will interview the patient about their experience of trial participation and of the inforatio technique.

  10 months

• Staff acceptability

  Assessed qualitatively by interviews with the staff at the outpatient clinics (wound care nurses and podiatrists)

  10 months

• Qualitative assessment of the inforatio technique

  The method of inforatio technique application will be qualitatively assessed by the applicant. The applicant will report any issues or complications regarding the inforatio technique definition.

  5 months. At baseline application and at the 21-day applications.

Study Arms (1)

Feasibility trial group

EXPERIMENTAL

Every trial patient will receive the intervention (the inforatio technique) that is intended for the definitive randomized clinical trial.

Procedure: Inforatio technique

Interventions

Inforatio technique PROCEDURE

We define the inforatio technique as punch biopsies taken in the periphery of the wound bed. The punch biopsies will have a diameter of two mms. The depth of the biopsies is primarily based on clinical assessment on distance to bone by assessment with a sterile wound probe and with attention to location and anatomy. The maximum depth will be 3.5 millimeters. The biopsies will be taken from one to two mms from the wound edges and with a distance of five mms between the biopsies. Inforatio technique is applied after standard care and wound assessment.

Feasibility trial group

Eligibility Criteria

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

You may qualify if:

• We include diabetic patients with foot ulcers that are more than six weeks old and which are located distal to the malleoli.
• The diameters of the ulcers must be at least four mms. One wound from each foot of a patient can be included. If a patient's foot have more than one ulcer that meets the abovementioned criteria, the biggest wound is included. If there is no difference in size, the wound that has the most recent onset is included. If two wounds are close to each other and separated by less than 5 mm intact skin, we will consider it as one wound.
• Wound onset estimates will be patient-reported.

You may not qualify if:

• We exclude following patients:
• Patients with dementia and other patients who are not able to give their informed consent.
• Patients with gangrene, necrosis deeper than 1mm, osteomyelitis and clinical signs of infection in their foot. Infection is identified by clinical assessment based on the classical signs comprising oedema, pain, warmth, redness and purulent exudates and is assessed by an experienced orthopedic surgeon.
• Patients with ulcers that have positive probe-to-bone test and visible joint and tendons
• Patients with systolic toe pressure of \< 20 mmHg
• Patients that, since the onset of their present foot ulcer, underwent vascular surgery in the lower extremity with the same laterality as the foot ulcer.
• Patients that, since the onset of their present foot ulcer, underwent surgical off-loading and amputations
• Patients that, since the onset of their present foot ulcer, underwent surgical wound revisions in an operating room.
• Patients that have an acute phase of Charcot arthropathy in the foot that presents with a foot ulcer.
• Patients that take systemic immunosuppressive drugs.
• Patients with cancer
• Patients with scleroderma

Sponsors & Collaborators

• Zealand University Hospital: lead

Study Sites (2)

Herlev University Hospital, Department of Orthopaedic Surgery

Herlev, 2730, Denmark

Location

Zealand University Hospital, Department of Orthopaedic Surgery

Køge, 4600, Denmark

Location

Related Publications (17)

• 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 N, Dorrian J, Fitzgerald P, MacDonald R, Rutks I, Wilt T. Advanced Wound Care Therapies for Non-Healing Diabetic, Venous, and Arterial Ulcers: A Systematic Review [Internet]. Washington (DC): Department of Veterans Affairs (US); 2012 Nov. Available from http://www.ncbi.nlm.nih.gov/books/NBK132238/

  PMID: 23586115 BACKGROUND

• Game FL, Apelqvist J, Attinger C, Hartemann A, Hinchliffe RJ, Londahl M, Price PE, Jeffcoate WJ; International Working Group on the Diabetic Foot. Effectiveness of interventions to enhance healing of chronic ulcers of the foot in diabetes: a systematic review. Diabetes Metab Res Rev. 2016 Jan;32 Suppl 1:154-68. doi: 10.1002/dmrr.2707.

  PMID: 26344936 BACKGROUND

• Braun LR, Fisk WA, Lev-Tov H, Kirsner RS, Isseroff RR. Diabetic foot ulcer: an evidence-based treatment update. Am J Clin Dermatol. 2014 Jul;15(3):267-81. doi: 10.1007/s40257-014-0081-9.

  PMID: 24902659 BACKGROUND

• Eldridge SM, Chan CL, Campbell MJ, Bond CM, Hopewell S, Thabane L, Lancaster GA; PAFS consensus group. CONSORT 2010 statement: extension to randomised pilot and feasibility trials. BMJ. 2016 Oct 24;355:i5239. doi: 10.1136/bmj.i5239.

  PMID: 27777223 BACKGROUND

• Braun L, Kim PJ, Margolis D, Peters EJ, Lavery LA; Wound Healing Society. What's new in the literature: an update of new research since the original WHS diabetic foot ulcer guidelines in 2006. Wound Repair Regen. 2014 Sep-Oct;22(5):594-604. doi: 10.1111/wrr.12220.

  PMID: 25139424 BACKGROUND

• SIGN. 116 Management of diabetes. A national clinical guideline. 2017; Available from: https://www.sign.ac.uk/assets/sign116.pdf

  BACKGROUND

• NICE Guideline. Diabetic foot problems: prevention and management [Internet]. [cited 2019 Jan 3]. Available from: https://www.nice.org.uk/guidance/ng19

  BACKGROUND

• Rogers LC, Bevilacqua NJ, Armstrong DG, Andros G. Digital planimetry results in more accurate wound measurements: a comparison to standard ruler measurements. J Diabetes Sci Technol. 2010 Jul 1;4(4):799-802. doi: 10.1177/193229681000400405.

  PMID: 20663440 BACKGROUND

• Schweitzer ME, Daffner RH, Weissman BN, Bennett DL, Blebea JS, Jacobson JA, Morrison WB, Resnik CS, Roberts CC, Rubin DA, Seeger LL, Taljanovic M, Wise JN, Payne WK. ACR Appropriateness Criteria on suspected osteomyelitis in patients with diabetes mellitus. J Am Coll Radiol. 2008 Aug;5(8):881-6. doi: 10.1016/j.jacr.2008.05.002.

  PMID: 18657783 BACKGROUND

• Julious SA. Sample size of 12 per group rule of thumb for a pilot study. Pharm Stat [Internet]. 2005;4(4):287-91. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/pst.185

  BACKGROUND

• Cocks K, Torgerson DJ. Sample size calculations for pilot randomized trials: a confidence interval approach. J Clin Epidemiol. 2013 Feb;66(2):197-201. doi: 10.1016/j.jclinepi.2012.09.002. Epub 2012 Nov 27.

  PMID: 23195919 BACKGROUND

• Whitehead AL, Julious SA, Cooper CL, Campbell MJ. Estimating the sample size for a pilot randomised trial to minimise the overall trial sample size for the external pilot and main trial for a continuous outcome variable. Stat Methods Med Res. 2016 Jun;25(3):1057-73. doi: 10.1177/0962280215588241. Epub 2015 Jun 19.

  PMID: 26092476 BACKGROUND

• O'Meara SM, Cullum NA, Majid M, Sheldon TA. Systematic review of antimicrobial agents used for chronic wounds. Br J Surg. 2001 Jan;88(1):4-21. doi: 10.1046/j.1365-2168.2001.01631.x.

  PMID: 11136304 BACKGROUND

• Teare MD, Dimairo M, Shephard N, Hayman A, Whitehead A, Walters SJ. Sample size requirements to estimate key design parameters from external pilot randomised controlled trials: a simulation study. Trials. 2014 Jul 3;15:264. doi: 10.1186/1745-6215-15-264.

  PMID: 24993581 BACKGROUND

MeSH Terms

Conditions

Diabetic Foot; Foot Ulcer; Diabetes Mellitus

Condition Hierarchy (Ancestors)

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

Study Officials

• Sahar Moeini, MD

  Zealand University Hospital Koege, Denmark

  PRINCIPAL INVESTIGATOR

• Hans Gottlieb, Chief consultant, MD PhD

  Herlev University Hospital, Denmark

  STUDY CHAIR

• Tue S Jørgensen, MD PhD

  Hvidovre University Hospital, Denmark

  STUDY CHAIR

• Malene RB Larsen, MD

  Zealand University Hospital Koege, Denmark

  STUDY CHAIR

• Stig Brorson, Professor, MD PhD DMsc

  Zealand University Hospital Koege, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The trial is a single-center single-group feasibility trial in outpatient clinical settings. The trial will be reported with reference to the extended CONSORT guidelines.

Study Record Dates

• First Submitted: March 25, 2019
• First Posted: June 13, 2019
• Study Start: March 20, 2019
• Primary Completion: September 26, 2019
• Study Completion: September 26, 2019
• Last Updated: October 30, 2019

Record last verified: 2019-10

Locations

DK (2)