Diabetic Foot UlcerNCT03985306
Treatment of Diabetic Foot Ulcers With Inforatio Technique to Promote Wound Healing
A study testing Inforatio technique in people with Diabetic Foot Ulcer and Diabetic Foot, run by Zealand University Hospital at 2 sites in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Foot Ulcer, Diabetic Foot, Wound Heal
- What is being tested?
- Inforatio technique
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesDenmark
- Study dates
- 20 Mar 2019to 26 Sep 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 12Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
Denmark2 sites
Herlev University Hospital, Department of Orthopaedic Surgery
Herlev, 2730
Zealand University Hospital, Department of Orthopaedic Surgery
Køge, 4600
About this study
Official title: Treatment of Diabetic Foot Ulcers With Inforatio Technique to Promote Wound Healing: a Feasibility Trial
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.
Read the detailed description
BACKGROUND
The prevalence of diabetic foot ulcers is expected to increase considerably due to a continuously increasing prevalence of diabetes. The healing process of diabetic foot ulcers is complicated by a complex pathophysiology of the distal lower extremities and a constant exposure to bacteria and pressure. Improving healing of diabetic foot ulcers will have several benefits including higher quality of life, reduced morbidity, reduced mortality and lower socioeconomic costs. Nonetheless, there are few randomized controlled clinical trials on surgical and non-surgical treatment chronic foot ulcers and many studies on the topic have a low level of evidence.
TRIAL AIMS
The investigators aim to assess the feasibility of conducting a definitive randomized controlled trial by exploring recruitment, patient acceptability, protocol adherence and adverse effects.
The success criteria of the trial is as follows:
- Weekly recruitment rates at two patients or more.
- Time from first outpatient visit to recruitment at 21 days or less.
- Retention rate at 90-day follow-up at 50% or more
- No appearance of unacceptable adverse effects In addition, the trial aims to assess logistic concerns regarding the trial and to improve the method of inforatio application.
Based on findings from the feasibility trial, the investigators may amend the design of the definitive trial.
RECRUITMENT
Patients are eligibility-screened and identified by the primary investigator and wound care staff when patients visit wound outpatient clinics at the recruiting facilities.
INCLUSION AND FOLLOW-UP
Eligible patients are included if they give their oral and written consent to participate. The baseline trial visit take place on the day that patients give their consent to participate.
The trial comprises a 90-day clinical follow-up. Follow-up visits will be at 10, 21, 42 and 90 days after baseline (give or take 3 days). Wounds are assessed at each trial visit. The inforatio technique is applied at baseline and again at the 21-follow-up day if the wound still has a diameter larger than four mms. Participants unable to attend at the precise dates for midtrial follow-up will be eligible for follow-up three days before or after the intended date. The participants who cannot attend during this window will skip the follow-up day in concern. If the participants miss the second intervention at the 21-day follow-up, they are excluded. For the 90-day follow-up, participants are recalled two times by the primary investigator within two weeks before being excluded.
Participants exit from the trial if following occurs during follow-up:
- they undergo surgeries described in the exclusion criteria
- they get acute signs of infection, gangrene or osteomyelitis in their foot in concern
- their tendons, joints or bone become exposed in the wound bed
- they develop an acute phase of charcot arthropathy in their foot in concern
- they get admitted for reasons related to their foot ulcer
- they die or emigrate
The trial is stopped if the intervention shows an unintended effect or potential harm.
TRIAL STANDARD TREATMENT
The participants receive a trial standard treatment at every trial visit. The treatment is conducted by the primary investigator in cooperation with wound care nurses and podiatrists. The standard treatment is defined based on Danish National guidelines, local guidelines of the recruiting facilities and guidelines of the National Institute for Health and Care Excellence.
The treatment is based on a flowchart that individualizes treatment based on clinical wound characteristics.
INFORATIO TECHNIQUE
The technique is described in the Arms and Interventions section.
TRIAL MEASURES
Wound assessment: Wounds are assessed at every trial visit. To monitor the ulcer area during follow-up, the investigators will analyze digital photos of the ulcer by using Image J which is a wound planimetry software. The depth of the ulcers are measured with sterile wound probes and reported by intervals of 5 millimeters. Undermining will be assessed with the same method as for depth and in intervals of 5 millimeters.
Microbial samples: At both stages of inforatio application, three punch biopsies are sent for cultivation to analyze bacterial species, bacterial load and resistance patterns of the bacteria.
Patient and staff interviews: described in the Outcome Measures section
STATISTICAL ANALYSIS
With descriptive statistics participants' demographics, the quantitative success criteria, the quantitative outcome measures and time to healing will be reported. Clinical healing is defined by intact epithelia.
The investigators will use statistical software SPSS version 21.0 (IBM Corp., Armonk, New York).
SAMPLE SIZE CONSIDERATION
Because effectiveness is not evaluated, a formal power calculation is not considered necessary for the objectives of a feasibility trial.
To minimize the number of patients that are exposed to a new intervention meanwhile keeping a level of precision for the variance estimate, the rule of thumb by Julious et al will be used for determination of the trial sample size. Thus, 12 participants will be included in the trial. Julious et al argues that a sample size of 12 per group gives a sufficient precision of the mean and variance estimates. Other studies report rules of thumbs with larger sample size to gain sufficient power for a pilot or feasibility trial.
ETHICAL CONSIDERATIONS AND RISK ASSESSMENT OF SIDE EFFECTS
The procedure of the intervention is small with an expectedly small risk of harm outcomes. The punch biopsies from the inforatio technique is relatively shallow therefore it is not expected that it will penetrate important anatomical structures or expose bone.
The primary investigator's clinical assessment, patient preference and patient tolerance is taken into consideration before inforatio technique is applied. Minimal discomfort is expected for the participants when they receive the inforatio technique treatment. Previous applications by the investigators showed that patients reported no or little pain during application.
The inforatio technique treatment has previously shown potential to improve healing thus participants may gain an improvement in healing of their foot ulcers.
If this trial shows that a definitive randomised clinical trial will be feasible, the investigators will examine the effect of inforatio technique through a larger randomised clinical trial. If the inforatio technique shows significant positive effect on time to healing it would become of great importance for future diabetic foot ulcer patients. The inforatio technique would become an addition to available therapeutic options. The technique is simple and only requires a punch biopsy tool. Nurses and general practitioners can be potential applicants that apply the treatment at clinics close to patient habitats making visits for wound treatment more convenient for the patients. If there is a significant positive effect on healing, it is expected that it will result in reduction of hospital admissions and less surgical interventions including amputations.
This project may contribute to more focus on treatment of patients with diabetic foot ulcers - a field of research that still needs studies to enable evidence-based treatment.
Inspectors from The National Committee of Health Research Ethics will have the authorization to quality control the trial.
COMPETING INTERESTS
The trial investigators declare that they have no competing interests.
- Conditions
- Diabetic Foot Ulcer, Diabetic Foot, Wound Heal, Ulcer Foot, Ulcer Healing
- Being tested
- Inforatio technique
- Keywords
- Diabetic foot ulcer, Wound treatment, Inforatio technique, Diabetes, Foot ulcer, Outpatient clinic, Feasibility trial, Punch biopsy, Foot ulcer treatment
- Medical subject headings
- Diabetic Foot, Foot Ulcer, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inforatio techniqueProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Feasibility trial group | Experimental | Every trial patient will receive the intervention (the inforatio technique) that is intended for the definitive randomized clinical trial. Receives: Procedure: Inforatio technique |
What is being measured
The primary outcome is the main question the study is designed to answer.
Eligibility rates
Descriptive statistics of number and rate of eligible patients during the period of recruitment
Measured: 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.
Measured: 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)
Measured: 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
Measured: 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.
Measured: 10 months
Retention rates
To investigate protocol adherence, the number and rate of participants that adhere to follow-up will be reported.
Measured: 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.
Measured: 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.
Measured: 10 months
Rate of eligible patients that accept participation
A quantitative investigation of patient acceptability.
Measured: At baseline, each follow-up visit and when patients drop out.
Qualitative assessment of patient acceptability
Assessed by interviews with participants.
Measured: 10 months
Observed harms and unexpected effects
Observed harms and unexpected effects observed by the investigators and staff will be reported.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 10 months
Time to healing of the foot ulcers
The investigators will report mean and variance of time to healing
Measured: 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.
Measured: 10 months
Staff acceptability
Assessed qualitatively by interviews with the staff at the outpatient clinics (wound care nurses and podiatrists)
Measured: 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.
Measured: 5 months. At baseline application and at the 21-day applications.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2019
- Study start20 Mar 2019
- Primary completion26 Sep 2019
- Study completion26 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for Diabetic Foot UlcerStudies of the same condition, open and under way.
- More trials run by Zealand University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zealand University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sahar Moeini, MD, Principal investigator, Zealand University Hospital Koege, DenmarkHans Gottlieb, Chief consultant, MD PhD, Study chair, Herlev University Hospital, DenmarkTue S Jørgensen, MD PhD, Study chair, Hvidovre University Hospital, DenmarkMalene RB Larsen, MD, Study chair, Zealand University Hospital Koege, DenmarkStig Brorson, Professor, MD PhD DMsc, Principal investigator, Zealand University Hospital Koege, Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03985306
- Sponsor's protocol ID
- REG-122-2018
- Status last verified
- Oct 2019
- First submitted
- 25 Mar 2019
- Last updated
- 30 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 25614499Karri 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.
PubMed 26643047Zimny 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.
PubMed 15772900Greer 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/
PubMed 23586115Game 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.
PubMed 26344936Braun 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.
PubMed 24902659Eldridge 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.
PubMed 27777223Braun 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.
PubMed 25139424SIGN. 116 Management of diabetes. A national clinical guideline. 2017; Available from: https://www.sign.ac.uk/assets/sign116.pdf
NICE Guideline. Diabetic foot problems: prevention and management [Internet]. [cited 2019 Jan 3]. Available from: https://www.nice.org.uk/guidance/ng19
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.
PubMed 20663440Schweitzer 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.
PubMed 18657783Julious 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
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.
PubMed 23195919Whitehead 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.
PubMed 26092476
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Diabetic Foot Ulcers With Inforatio Technique to Promote Wound Healing: a Feasibility Trial
- ClinicalTrials.gov ID
- NCT03985306
- Acronym / sponsor ID
- REG-122-2018
- 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
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Zealand University HospitalUniversity, hospital or other
- Study start
- 20 Mar 2019 (actual)
- Primary completion
- 26 Sep 2019 (actual)
- Study completion
- 26 Sep 2019 (actual)
- First posted
- 13 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
BACKGROUND
The prevalence of diabetic foot ulcers is expected to increase considerably due to a continuously increasing prevalence of diabetes. The healing process of diabetic foot ulcers is complicated by a complex pathophysiology of the distal lower extremities and a constant exposure to bacteria and pressure. Improving healing of diabetic foot ulcers will have several benefits including higher quality of life, reduced morbidity, reduced mortality and lower socioeconomic costs. Nonetheless, there are few randomized controlled clinical trials on surgical and non-surgical treatment chronic foot ulcers and many studies on the topic have a low level of evidence.
TRIAL AIMS
The investigators aim to assess the feasibility of conducting a definitive randomized controlled trial by exploring recruitment, patient acceptability, protocol adherence and adverse effects.
The success criteria of the trial is as follows:
- Weekly recruitment rates at two patients or more.
- Time from first outpatient visit to recruitment at 21 days or less.
- Retention rate at 90-day follow-up at 50% or more
- No appearance of unacceptable adverse effects In addition, the trial aims to assess logistic concerns regarding the trial and to improve the method of inforatio application.
Based on findings from the feasibility trial, the investigators may amend the design of the definitive trial.
RECRUITMENT
Patients are eligibility-screened and identified by the primary investigator and wound care staff when patients visit wound outpatient clinics at the recruiting facilities.
INCLUSION AND FOLLOW-UP
Eligible patients are included if they give their oral and written consent to participate. The baseline trial visit take place on the day that patients give their consent to participate.
The trial comprises a 90-day clinical follow-up. Follow-up visits will be at 10, 21, 42 and 90 days after baseline (give or take 3 days). Wounds are assessed at each trial visit. The inforatio technique is applied at baseline and again at the 21-follow-up day if the wound still has a diameter larger than four mms. Participants unable to attend at the precise dates for midtrial follow-up will be eligible for follow-up three days before or after the intended date. The participants who cannot attend during this window will skip the follow-up day in concern. If the participants miss the second intervention at the 21-day follow-up, they are excluded. For the 90-day follow-up, participants are recalled two times by the primary investigator within two weeks before being excluded.
Participants exit from the trial if following occurs during follow-up:
- they undergo surgeries described in the exclusion criteria
- they get acute signs of infection, gangrene or osteomyelitis in their foot in concern
- their tendons, joints or bone become exposed in the wound bed
- they develop an acute phase of charcot arthropathy in their foot in concern
- they get admitted for reasons related to their foot ulcer
- they die or emigrate
The trial is stopped if the intervention shows an unintended effect or potential harm.
TRIAL STANDARD TREATMENT
The participants receive a trial standard treatment at every trial visit. The treatment is conducted by the primary investigator in cooperation with wound care nurses and podiatrists. The standard treatment is defined based on Danish National guidelines, local guidelines of the recruiting facilities and guidelines of the National Institute for Health and Care Excellence.
The treatment is based on a flowchart that individualizes treatment based on clinical wound characteristics.
INFORATIO TECHNIQUE
The technique is described in the Arms and Interventions section.
TRIAL MEASURES
Wound assessment: Wounds are assessed at every trial visit. To monitor the ulcer area during follow-up, the investigators will analyze digital photos of the ulcer by using Image J which is a wound planimetry software. The depth of the ulcers are measured with sterile wound probes and reported by intervals of 5 millimeters. Undermining will be assessed with the same method as for depth and in intervals of 5 millimeters.
Microbial samples: At both stages of inforatio application, three punch biopsies are sent for cultivation to analyze bacterial species, bacterial load and resistance patterns of the bacteria.
Patient and staff interviews: described in the Outcome Measures section
STATISTICAL ANALYSIS
With descriptive statistics participants' demographics, the quantitative success criteria, the quantitative outcome measures and time to healing will be reported. Clinical healing is defined by intact epithelia.
The investigators will use statistical software SPSS version 21.0 (IBM Corp., Armonk, New York).
SAMPLE SIZE CONSIDERATION
Because effectiveness is not evaluated, a formal power calculation is not considered necessary for the objectives of a feasibility trial.
To minimize the number of patients that are exposed to a new intervention meanwhile keeping a level of precision for the variance estimate, the rule of thumb by Julious et al will be used for determination of the trial sample size. Thus, 12 participants will be included in the trial. Julious et al argues that a sample size of 12 per group gives a sufficient precision of the mean and variance estimates. Other studies report rules of thumbs with larger sample size to gain sufficient power for a pilot or feasibility trial.
ETHICAL CONSIDERATIONS AND RISK ASSESSMENT OF SIDE EFFECTS
The procedure of the intervention is small with an expectedly small risk of harm outcomes. The punch biopsies from the inforatio technique is relatively shallow therefore it is not expected that it will penetrate important anatomical structures or expose bone.
The primary investigator's clinical assessment, patient preference and patient tolerance is taken into consideration before inforatio technique is applied. Minimal discomfort is expected for the participants when they receive the inforatio technique treatment. Previous applications by the investigators showed that patients reported no or little pain during application.
The inforatio technique treatment has previously shown potential to improve healing thus participants may gain an improvement in healing of their foot ulcers.
If this trial shows that a definitive randomised clinical trial will be feasible, the investigators will examine the effect of inforatio technique through a larger randomised clinical trial. If the inforatio technique shows significant positive effect on time to healing it would become of great importance for future diabetic foot ulcer patients. The inforatio technique would become an addition to available therapeutic options. The technique is simple and only requires a punch biopsy tool. Nurses and general practitioners can be potential applicants that apply the treatment at clinics close to patient habitats making visits for wound treatment more convenient for the patients. If there is a significant positive effect on healing, it is expected that it will result in reduction of hospital admissions and less surgical interventions including amputations.
This project may contribute to more focus on treatment of patients with diabetic foot ulcers - a field of research that still needs studies to enable evidence-based treatment.
Inspectors from The National Committee of Health Research Ethics will have the authorization to quality control the trial.
COMPETING INTERESTS
The trial investigators declare that they have no competing interests.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Feasibility trial group | Experimental | Procedure: Inforatio techniqueEvery trial patient will receive the intervention (the inforatio technique) that is intended for the definitive randomized clinical trial. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Inforatio techniqueWe 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. | Procedure or surgery | Feasibility trial group |
Primary outcome
Eligibility rates
Time frame: The first 2 months of the trial (untill the last patient has been recruited)
Descriptive statistics of number and rate of eligible patients during the period of recruitment
Refusal rates
Time frame: The first 2 months of the trial (untill the last patient has been recruited)
Descriptive statistics of number and rate of eligible patients that refuse trial participation.
Time from identification to inclusion
Time frame: The first 2 months of the trial (untill the last patient has been recruited)
Descriptive statistics of average time from eligible patients are identified to they are included in the trial (baseline trial visit)
Qualitative assessment of unexpected factors that must cause exclusion
Time frame: 10 months
Qualitatively assessed by the primary investigator
Rate of unexpected exclusion
Time frame: 10 months
Descriptive statistics of number and rate of patients that are excluded due to reasons not already covered by the trial definition of exclusion criteria.
Retention rates
Time frame: 10 months
To investigate protocol adherence, the number and rate of participants that adhere to follow-up will be reported.
Number of missed trial follow-up visits
Time frame: 10 months
To investigate protocol adherence, the number of missed trial visits will be reported for each participant.
Drop-out rates
Time frame: 10 months
To investigate protocol adherence, the number and rate of participants that choose to drop out during follow-up will be reported.
Rate of eligible patients that accept participation
Time frame: At baseline, each follow-up visit and when patients drop out.
A quantitative investigation of patient acceptability.
Qualitative assessment of patient acceptability
Time frame: 10 months
Assessed by interviews with participants.
Observed harms and unexpected effects
Time frame: 10 months
Observed harms and unexpected effects observed by the investigators and staff will be reported.
Patient-reported potential side effects
Time frame: 10 months
A qualitatively assessment of harms and unexpected effects by interviewing participants about potential side effects that they experience.
Qualitative assessment of logistics issues regarding outpatient clinic visits
Time frame: 10 months
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.
Time to healing of punch biopsy scars
Time frame: 10 months
The time to healing will be reported to estimate if and when observer blinding may be possible.
Qualitative assessment of the method of wound assessment.
Time frame: 10 months
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.
Qualitative assessment of the extent of qualitative patient measures
Time frame: 10 months
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.
Qualitative assessment of the feasibility of culturing 3 biopsies from each round of inforatio technique applications for a future definitive trial.
Time frame: 10 months
The investigators assess whether the included centers have the capacity to culture three biopsies two times from each patient.
Rates of wound treatments at trial visits that deviate from the trial standard treatment definition
Time frame: 10 months
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.
Qualitative assessment of wound care treatments received between trial visits and the deviations from the trial definition of standard treatment.
Time frame: 10 months
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.
Time to healing of the foot ulcers
Time frame: 10 months
The investigators will report mean and variance of time to healing
Patient-reported experience of trial participation and the inforatio technique
Time frame: 10 months
The investigators will interview the patient about their experience of trial participation and of the inforatio technique.
Staff acceptability
Time frame: 10 months
Assessed qualitatively by interviews with the staff at the outpatient clinics (wound care nurses and podiatrists)
Qualitative assessment of the inforatio technique
Time frame: 5 months. At baseline application and at the 21-day applications.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2019.
- Background: PubMed 25614499Andrews 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.
- Background: PubMed 26643047Karri 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.
- Background: PubMed 15772900Zimny 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.
- Background: PubMed 23586115Greer 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/
- Background: PubMed 26344936Game 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.
- Background: PubMed 24902659Braun 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.
- Background: PubMed 27777223Eldridge 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.
- Background: PubMed 25139424Braun 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.
- BackgroundSIGN. 116 Management of diabetes. A national clinical guideline. 2017; Available from: https://www.sign.ac.uk/assets/sign116.pdf
- BackgroundNICE Guideline. Diabetic foot problems: prevention and management [Internet]. [cited 2019 Jan 3]. Available from: https://www.nice.org.uk/guidance/ng19
- Background: PubMed 20663440Rogers 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.
- Background: PubMed 18657783Schweitzer 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sahar Moeini, MD principal investigator
Zealand University Hospital Koege, Denmark
Hans Gottlieb, Chief consultant, MD PhD study chair
Herlev University Hospital, Denmark
Tue S Jørgensen, MD PhD study chair
Hvidovre University Hospital, Denmark
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Inforatio technique in people with Diabetic Foot Ulcer and Diabetic Foot, run by Zealand University Hospital at 2 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Eligibility rates (time frame: The first 2 months of the trial (untill the last patient has been recruited)). The study lists 23 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03985306, which also lists 17 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2019; AzTrials last refreshed its copy on 8 Nov 2026.