Treatment of Diabetic Foot Ulcers With Inforatio Technique to Promote Wound Healing: A Feasibility Trial

Abstract

Chronic foot ulcers have extensive consequences for diabetic patients’ quality of life and increase risks of amputation and death. The aim of this trial was to assess the feasibility of conducting a larger clinical trial to evaluate the clinical effect of inforatio technique on healing of diabetic foot ulcers (DFUs). Inforatio technique is a novel minimal invasive procedure where small cuts are made on wound beds with punch biopsy tools. This study was a feasibility trial conducted at an outpatient wound care clinic at Zealand University Hospital. Twelve patients with DFUs were included. During a 90-day follow-up, participants visited the clinic 5 times and received inforatio technique twice. Feasibility was assessed with regard to recruitment, acceptability, burden, benefits, protocol adherence, and adverse events. The recruitment rate was 1 patient per eighth day (95% confidence interval [CI] = [4th-13th]), and the retention rate was 100% (95% CI = [74-100]). During follow-up, healing was observed for 4 ulcers (33%, 95% CI = [10-65]) with a mean time for healing of 59 days (range, 22-89) (95% CI = [5-113]). Five ulcers had a reduction of wound area and 3 ulcers had an increase in area from baseline to 90-day follow-up. No temporal relationship was found between inforatio application and wound area increase. There were no patient-reported harmful effects and no adverse events with probable relation to inforatio technique. Patient acceptability and participant adherence were promising. Thus, a larger clinical trial for evaluating the clinical effect of inforatio technique is considered feasible to conduct.

Keywords

diabetic foot ulcer chronic wound chronic ulcer DFU wound care wound treatment

Diabetic patients have a 15% to 25% lifetime risk of getting chronic foot ulcers. Meanwhile, the prevalence of diabetes mellitus is increasing worldwide.^1,2 Diabetic foot ulcers (DFUs) reduce patients’ quality of life and are associated with increased mortality, increased morbidity, and high socioeconomic costs.^1-4 Nonetheless, there are few randomized controlled clinical trials (RCTs) on the treatment of DFUs and the current level of evidence is low.^1,4-6

Inforatio technique is a novel minimal invasive procedure where small cuts are made on wound beds of chronic DFUs with punch biopsy tools. In these hard-to-heal DFUs, the inflammatory response is chronic and associated with tissue destruction.⁷ With inforatio technique, we apply small acute traumas to the wound bed tissue and thereby hope to reach controlled bleeding and to induce an acute inflammatory response that promotes healing. Prior to this feasibility trial, our research group made an unexpected qualitative observation when punch biopsies were taken from DFUs for basic research purposes. Formation of granulation tissue and epithelialization appeared to promote locally at sites where biopsies were taken from the wound bed. To the best of our knowledge, there are no previous studies about methods similar to the inforatio technique.

The aim of this trial was to (1) assess the feasibility of conducting a larger clinical trial to evaluate the clinical effect of inforatio technique on healing of DFUs and (2) to refine inforatio technique. If a larger clinical trial is assessed feasible to conduct, an RCT will be conducted with the aim of assessing the effect of inforatio technique on healing of DFUs compared to usual wound care.

Methods

Trial Design

The study was a single-group feasibility trial at the outpatient wound care clinic of Zealand University Hospital. The trial was reported according to the extended consolidated standards of reporting trials (CONSORT) 2010 statement for randomized pilot and feasibility trial except from sections regarding randomization.⁸ The trial was registered on ClinicalTrials.gov (reference ID: NCT03985306).

Ethics Approval and Consent to Participate

Ethical approval was obtained by The National Committee on Health Research Ethics (reference number SJ-746). Participants provided both oral and written informed consent before inclusion and international committee of medical journal editors (ICMJE) Recommendations for the Protection of Research Participants were followed.

Trial Participants

Inclusion Criteria

Diabetic patients above 18 years of age with chronic ulcers located distal to the malleoli and wound diameters >4 mm were considered for inclusion. Ulcers with patient-reported wound duration >6 weeks were defined as chronic. If a patient had >1 eligible ulcer, the largest ulcer was included. In case of equally sized ulcers, the ulcer with the most recent onset was included. Two ulcers separated by <5 mm intact skin were defined as 1 ulcer.

Exclusion Criteria

Patients were excluded if they had (1) dementia or other cognitive impairments; (2) malignant disease; (3) scleroderma; (4) consumption of systemic immunosuppressive drugs; (5) gangrene, osteomyelitis, infection or acute phase Charcot arthropathy in the index extremity; (6) severe critical ischemia in the index foot, defined as nonpalpable pulse accompanied by systolic toe pressure <20 mmHg; or (7) surgical wound revision in a theater, surgical offloading, amputation, or vascular surgery of the affected extremity since the onset of the index ulcer. Ulcers with necrosis deeper than 1 mm; positive probe-to-bone test; visible joint; or visible tendon were excluded. Infection was defined according to the criteria of the Infectious Diseases Society of America and the IWGDF.^9,10

Recruitment and Informed Consent

The staff at the wound outpatient clinic screened patients with DFUs. When eligible patients were identified, they were presented to the trial and were offered written information. Within a week from identification, the primary investigator contacted eligible patients by phone or e-mail and offered an informative meeting were patient could give their consent if they wished to participate.

Follow-up

There were 5 trial visits during a total follow-up of 90 days. The visits were at baseline, 10, 21, 42, and 90 days. The inforatio technique was applied at baseline and again at 21-day follow-up if the wound still had a diameter >4 mm. The 10-, 21- and 42-day follow-ups were missed if participants were unable to attend within 3 days before or after the intended day for follow-up. For explorative reasons and to improve data on trial objectives, the following amendments to protocol were decided after trial commencement:

If participants consented to it at 90-day follow-up, staff reported healing observed at outpatient clinic visits after end of follow-up and until 140 days had passed from baseline.

If infection; osteomyelitis; gangrene; or exposure of bone, tendon, or joint developed during follow-up, participants would not exit the trial. Instead, participants would continue follow-up without receiving inforatio technique again, and their data on trial objectives would be included in the analysis of feasibility. The mentioned events would be treated by orthopedic surgeons according to local guidelines.

Standard Treatment

At each trial, visiting participants received a standard treatment that included wound care and offloading treatment performed by the staff at the outpatient clinic. Wound care consisted of (1) surgical debridement of slough, devitalized tissue and callosities; (2) cleansing of the ulcer; and (3) application of dressings that promoted a moist wound environment.^11,12 The staff, which comprised 2 experienced podiatrists, chose dressings based on their clinical assessment and experience. When ulcers were dry or macerated, written instruction on wound care was given to participants for delivery to personnel that performed wound care between trial. Offloading treatment was assessed by an orthopedic surgeon or podiatrist before trial inclusion. Offloading was assessed at each trial visit by the staff and was adjusted when necessary.

Inforatio Technique

Inforatio technique is a minimal invasive procedure where small cuts are made with punch biopsy tools in the periphery of wound beds, see Figures 1 and 2. The technique is applied after debridement and cleansing of ulcers. Each cut is called an inforatio. The punch biopsy tools had a diameter of 2 mm. The depth of each inforatio was <3.5 mm and depended on the underlying anatomy. The predefined pattern of the inforatio technique was 1 to 2 mm distance from wound edges, and 5 mm distance between each inforatio. Distances were measured with sterile probes marked for every 1 cm. Due to neuropathy of the feet of participants and the minimal invasive nature of the procedure, it was conducted without any use of analgesia. The application would be stopped if participants experienced pain. The inforatio technique was applied by the primary investigator who was a physician.

Wound Size Measurement

Photographs of the ulcers were taken at each trial visit with an Olympus VG-160 14 Megapixel Camera at an approximate distance of 30 cm and an angle of 90° on the wound bed. Photographs that were taken after debridement and before inforatio technique were applied. Rulers next to the ulcers were used as size references. Wound area was calculated by digital planimetry with ImageJ software.¹³ Areas were measured 5 times on each photograph and average wound area was based on the 3 middle values. Planimetry was performed by a blinded observer who was a wound care nurse with previous experience in digital planimetry. Digital planimetry has been reported as one of the most accurate and reliable methods for area measurement.^13-15 And several studies suggest ImageJ for digital planimetry.^16-20 Complete wound healing was defined as complete epithelialization without any discharge from the site of the index ulcer.¹⁰

Trial Objectives

Feasibility

Recruitment was assessed based on (1) eligibility rate; (2) recruitment rate; and (3) time from patient identification to baseline. Unexpected factors that caused exclusion were recorded and suitability of the eligibility criteria was qualitatively assessed. The proportion of healed ulcers during both the 90-day and the extended 140-day follow-up was recorded to enable sample size estimation for a future RCT.

Patient acceptability to trial participation and to the inforatio technique was assessed based on patient-reported reasons for refusal of participation and interviews with participants at 90-day follow-up or after attrition. The interviews included questions about trial experience and suggestions for change of the trial setup. Participant adherence was assessed by the retention rate and the rate of missed trial visits and participants were interviewed about reasons for attrition and missed trial visits.

Staff acceptability was based on interviews with the staff about burden of the trial.

To assess sufficiency of wound care between trial visits, the staff and primary investigator reported observations of dryness or macerations at trial visits.

Participant burden was assessed by participant interviews at 90-day follow-up or after attrition; trial visit durations; and proportion of trial visits that were coordinated with other appointments at the outpatient clinic or other departments at the same hospital. Some trial visits, unexpectedly, facilitated a faster initiation of nontrial examinations. Thus, type and frequency of benefits were reported to assess participant benefit.

Participants were interviewed at each trial visit about harmful and unexpected effects of inforatio technique. Investigator and staff observations of adverse events were reported including events of infection, acute Charcot arthropathy, and amputation. The research group qualitatively assessed the relation of adverse events to inforatio technique according to the following categories: (1) definitely related—the event can be fully explained by the application of inforatio technique; (2) probably related—the event is most likely to be explained by the application of inforatio technique rather than other treatments received or by the participant's clinical condition; and (3) probably not related—the event is most likely to be explained by other treatments received, by an expected natural course of DFUs, or by the participant's clinical condition.

Assessment of Inforatio Technique

To refine the procedure, inforatio technique was qualitatively assessed by the applicant. Visibility of inforatio scars on photographs was recorded at 10- and 42-day follow-up to assess when observer blinding is possible.

Sample Size Considerations

The trial was designed to assess feasibility and not effect. Thus, sample size was not estimated by a formal power calculation. To minimize the number of patients who were exposed to a novel procedure, meanwhile keeping a level of precision for estimating mean and variance of time for healing, we followed the recommendations by Julious²¹ of including 12 patients per group. We did not assess the feasibility of randomization and therefore a single group of 12 patients was included.

Statistics

Baseline participant characteristics and wound characteristics were reported descriptively. Of the feasibility outcomes, mean and range were reported for continuous outcomes, and raw count was reported for nominal outcomes. Recruitment rate, retention rate, rate of missed trial visits, time to healing, and proportion of healed ulcers were reported with 95% CIs. Qualitative outcomes were narratively reported. We used statistical software SPSS version 25.0 (IBM Corp.).

Results

Feasibility

Recruitment. Twelve patients were recruited from March 20 to June 27, 2019 and follow-up ended on September 26, 2019, see Figure 3. See Tables 1 and 2 for baseline characteristics. The recruitment rate was 1 per eighth day (95% CI = 4-13). Mean time from identification to baseline trial visit was 6 days (range, 0-19). There were no unexpected factors that caused exclusion. During follow-up, healing was observed for 4 ulcers (33%, 95% CI = [10-65]) with a mean time for healing of 59 days (range, 22-89) (95% CI = [5-113]). Five ulcers had a reduction of wound area and one of these was the ulcer of patient 12 who had full epithelization but still had wound discharge at the 90-day follow-up. Three ulcers had an increase in area from baseline to 90-day follow-up, see Figure 4 and Table 3. The average baseline wound duration was 4 months (range, 1 ½ -6 ½) for healed ulcers, 8 months (range, 1 ½-18) for ulcers with reduction in area, and 24 months (range, 3 ½-90) for ulcers that increased in area. After 90-day follow-up, healing was observed for patients 1 and 2 within 140 days from baseline. Patients 4, 5, 6, and 10 did not heal within 140 days. Patients 9 and 12 could not be followed after 90-day follow-up because they did not have visits at the outpatient clinic.

Table 1.

Baseline Index Foot and Index Ulcer Characteristics.

Patient	Baseline wound area (mm²)	Ulcer duration (months)	Ulcer location	Palpable pulse	Toe pressure (mmHg)	Neuropathy
1	34	4 ½	Plantar aspect of forefoot	No	48	Yes
2	13	8 ½	Dorsal aspect of toe	Yes	N/A	Yes
3	18	6 ½	Lateral aspect of the dorsum of the foot	Yes	N/A	Yes
4	51	7 ½	Plantar aspect of forefoot	Yes	N/A	Yes
5	214	>60	Dorsal aspect of toe	Yes	N/A	Yes
6	73	3 ½	Plantar aspect of forefoot	Yes	N/A	Yes
7	60	3 ½	Dorsal aspect of toe	Yes	N/A	Yes
8	67	1 ½	Posterior aspect of heel	Yes	N/A	Yes
9	46	9 ½	Plantar aspect of forefoot	Yes	N/A	Yes
10	26	1 ½	Plantar aspect of forefoot	Yes	N/A	Yes
11	51	5	Posterior aspect of heel	Yes	N/A	Yes
12	205	18	Plantar aspect of toe	Yes	N/A	Yes

Abbreviation: N/A, not available.

Table 2.

Baseline Participant Characteristics.

Patient	Sex	Age	Diabetes type	Smoking	Alcohol abuse
1	Male	67	2	Previous	No
2	Male	85	1	Previous	No
3	Male	55	1	No	No
4	Male	76	2	Previous	No
5	Male	87	2	Previous	No
6	Male	40	2	No	No
7	Male	56	2	No	Previous
8	Female	64	2	No	No
9	Male	55	2	No	No
10	Male	60	2	No	No
11	Female	83	2	Previous	No
12	Male	63	2	Previous	No

Table 3.

Wound Area Progression During 90-day Follow-up.

Patient	Baseline (mm²)	10-day follow-up (mm²)	21-day follow-up (mm²)	42-day follow-up (mm²)	90-day follow-up (mm²)
1	34	19	18	14	14
2	13	151	185	169	7
3	18	15	14	2	Complete healing
4	51	N/A^a	26	12	13
5 (↑)	214	284	383	355	257
6 (↑)	73	58	70	67	117
7	60	N/A^a	Complete healing	N/A^a	Complete healing
8	67	30	24	Complete healing	Complete healing
9 (↑)	46	36	81	71	70
10	26	9	25	15	19
11	51	42	18	11	Complete healing
12	205	109	208	N/A^b	0

Measurement missing due to missed trial visit.

Measurement missing due to poor quality of photograph.

Columns for baseline and 21-day follow-up are italicized to illustrate the visits at which inforatio technique was applied. Visits subsequent to inforatio application were 10-day and 42-day follow-ups. Bold values illustrate when a wound area increase was observed from a day of inforatio application to the subsequent trial visit. Two cases of wound area increase were observed from baseline application to 10-day follow-up and none from 21-day application to 42-day follow-up.

Abbreviations: N/A: not available; ↑, participants with total wound area increase from baseline to 90-day follow-up.

Patient acceptability. Two eligible patients refused participation for the following reasons: one did not want an experimental treatment and the other showed interest in the trial but did not feel that he had the stamina to participate in a clinical trial due to strong postoperative pain in the contralateral foot. Ten participants reported a positive experience of participation and 2 participants experienced no difference from their usual outpatient care. All participants reported that they felt safe about receiving inforatio technique. Four participants believed that healing had accelerated after each time inforatio technique was applied. Therefore, two of these participants suggested that inforatio technique would be applied more often during follow-up. No other change to trial set-up was suggested.

Participant adherence. The retention rate was 100% (95% CI = [74-100]). Three of 60 visits were missed (5%, 95% CI = [1-14]). One participant missed 10- and 42-day follow-up due to illness. Another participant missed a 10-day follow-up due to holidays and appointments at other hospitals.

Staff acceptability. The staff reported a positive experience of the trial but trial visits were often longer than nontrial visits due to extensive data collection. Thus, the staff wished to have 1 h for trial visits instead of the usual 30 min for nontrial visits at the outpatient clinic. The staff reported that the 10-day follow-up was, in most cases, an unnecessary visit for participants’ nontrial-related care at the clinic. Otherwise, trial visits were reported as coherent with participant's need for nontrial-related care.

Sufficiency of wound care between trial visits. Maceration of index ulcers was observed in 5 participants and dryness of index ulcers were observed in 3 participants. For patient 5, both the index ulcer and a nearby ulcer became dry and increased in area while treated at home with an unknown dressing, see Figure 5. Patient 9 used curettes to debride callosities and macerated wound edges by himself. Six participants received written instructions during follow-up due to either maceration or dryness of their ulcer. After instructions were given, 5 of 6 participants had improvements in the clinical appearance of their wound at the following trial visit. No information was found about wound care between trial visits in participants’ medical records.

Participant burden. One participant reported waiting time at the clinic as a burden but was also one of six participants that reported the increased frequency of visits as a benefit. No other burdens were reported. The mean time of trial visits was 50 min (range, 25-90) when including time for treatments and examinations for nontrial purposes, eg treatments of nonindex ulcers. Thirty-five of 57 trial visits were on the same day as nontrial appointments at the outpatient clinic. An additional trial visit was on the day of a nontrial appointment at the same hospital. One of the 3 missed trial visits were planned with an appointment for nontrial purposes.

Participant benefit. Three participants had nonindex ulcers that were examined and treated more often at the outpatient clinic due to trial participation. Two participants had an acceleration of diagnostic evaluations because trial visits were coordinated at days of examination at the same hospital. Thus, 1 participant had an assessment of an MRI on the same day he was scanned and another participant was referred to a vascular surgical department on the day of a distal blood pressure examination.

Patient-reported harmful and unexpected effects. There were no patient-reported harmful effects. None of the participants experienced pain from inforatio technique nor needed analgesic drugs during or after the procedure. Patients 1 and 9 reported the following positive effects: a throbbing feeling in the index ulcer for 1 day after inforatio and reduction of tension and pain in the index foot, respectively. Patient 9 also reported numbness of the index foot for 30 min after inforatio as an indifferent effect.

Adverse events: Two participants had bleedings after inforatio that were resistant to 5 min compressions but stopped after application of an absorbable hemostatic gelatin sponge and 10 to 15 min of compression. This was an event that was definitely related to inforatio technique but was not considered an adverse event either by participants or by staff because the bleeding was possible to control. As with debridement, it was preferable to reach bleeding.

Patients 5, 6, and 9 had a total wound area increase during follow-up but there was no temporal relation between application of inforatio technique and wound area increase in these patients (Table 3). From days of inforatio application to subsequent trial visits, an increase in wound area was seen from baseline to 10-day follow-up in patients 5 and 2 and none from 21-day to 42-day follow-up, see Table 3. The wound expansions at 10-day follow-up were accompanied by maceration in patient 2 and dryness in patient 5. Maceration did not reoccur after the second application of inforatio technique in patient 2 and patient 2 had a total decrease in wound area from baseline to 90-day follow-up. Maceration of patient 2’s ulcer at 10-day follow-up might have been due to insufficient wound care or the shoes that he wore against our recommendations. After written instructions on wound care were given to patient 5 at 21-day follow-up, the index ulcer and an adjacent ulcer changed from dry to moist and both reduced in area, see Figure 5. The shortest distance between the 2 ulcers of patient 5 was 1.7 cm. The concurrent wound area progression of a nonindex ulcer in patient 5, indicated that other factors than inforatio technique caused an increase in wound area from baseline to 21-day follow-up. Based on the observations mentioned in this section, we found no systematic pattern between inforatio application and wound area increase. Thus, we do not consider it a probable adverse event related to inforatio technique.

Patient 1 had a white purulent discharge and tenderness from the index ulcer at 42-day follow-up but no redness, swelling, or warmth. After 1 week of antibiotic treatment, clinical signs of infection did not reoccur and wound area began to decrease. Infection is a well-known natural cause for many DFUs. Thus, a mild infection observed in 1 of 12 participants 21 days after inforatio application is probably related to the natural course of DFUs rather than inforatio technique. No participants developed osteomyelitis, had amputations, developed acute Charcot arthropathy, or died during follow-up. None of the applied inforatios exposed bone or tendon.

Assessment of Inforatio Technique

Probes were pressed gently on the wound bed to estimate the distance to the underlying bone before inforatio was performed and inforatio was avoided on sites where the distance to the underlying bone was too short to allow the procedure without reaching the bone. A maximum depth of 3.5 mm was ensured by using half the length of the punch biopsy steel band as control. Distances between each inforatio were 3 to 6 mm and distances from wound edges were 1 to 3 mm. Discrete visible scars from inforatio technique were observed for 2 participants at the 10-day follow-up by the staff at the clinic. However, the blinded observer did not observe any scars from inforatio on photographs of the ulcers. No participants had visible scars at the 42-day follow-up.

Discussion

There were no patient-reported harmful effects and no adverse events that were probably related to inforatio technique. Patient acceptability, staff acceptability, and participant adherence were promising. However, higher attrition rates are expected in larger trials, especially if follow-up is prolonged.⁵ Thus, a multicenter trial design must be considered to achieve higher recruitment rates in a future trial.

We aimed to avoid strict eligibility criteria to achieve high-external validity in a future trial that assesses clinical effect. However, an upper limit for wound duration must be considered for a future trial because healing of DFUs of long duration is often inhibited by complex interactions of different factors.⁵ An article about reporting standards of studies on the management of DFUs recommends wound durations of >12 or 24 months as an exclusion criterion.⁵

Ulcer healing has been recommended as a clinically meaningful endpoint in studies on treatment of DFUs.^5,22 When healing is the primary outcome, a follow-up >90 days may improve estimates on clinical effect. Jeffcoate et al⁵ recommend a follow-up of 16, 20, or 24 weeks when healing is the primary outcome in studies on treatment of DFUs. Change in ulcer area can be a surrogate measure for clinical effect and patient-reported outcome measures will be an important secondary outcome measure in a future trial.⁵ As the underlying mechanisms behind the suggested effect are not fully understood, our approach to this novel treatment modality is purely empirical. The underlying mechanisms will be further investigated in future explanatory studies if a substantial clinical effect is found in an RCT. It is not unusual that 4 of 12 DFUs heal within a 90-day follow-up. A systematic review based on 4 RCTs reported that 24% of neuropathic, noninfected DFUs healed during a 90-day follow-up and 30% during a 140-day follow-up when receiving standard treatment, which comprised debridement, offloading, and either saline-moistened gauze or placebo gel with gauze.²³ Previous RCTs have reported that 21% to 30% of noninfected diabetic ulcers healed after 90 days in control groups that received standard treatment, which comprised debridement; offloading; and either moistened gauze, foam dressings, or collagen alginate.^24-26

We were able to follow 10 patients for 140 days and of these, 6 of 10 had healing of their index ulcer. One of the 4 patients who did not achieve healing had an ulcer duration of >4 years. For the sample size calculation of a future RCT with a 140-day follow-up, we suggest that the expected proportion of healing is set at 60% for the intervention group that receives inforatio technique, especially if wound duration of >2 years is an exclusion criterion.

Reasons for nonhealing of DFUs are complex and multifactorial and increase in wound area can be expected as a natural course for some ulcers. Of the 3 patients who had a total wound area increase during follow-up, we found no temporal relationship between the increase in wound area and visits at which inforatio was applied. Baseline routine delivery of written instructions on wound care may reduce deviations in wound care between trial visits and thereby reduce bias when estimating the intervention effect on healing in a future trial by.

According to our definition,^9,10 patient 1 had an infection of his index ulcer at 42-day follow-up. Infection is a well-known natural course for many DFUs.^27,28 The Eurodiale study included 1229 patients and reported that 58% of the ulcers developed infection during a 1-year follow-up.²⁹ Despite the transient infection, the wound area of patient 1 decreased and healing was observed within 140 days from baseline.

Based on the trial results, it is feasible to apply inforatio technique more frequently without harms. An increase in continuity of the intervention will increase the feasibility of detecting the clinical effect.

Limitations

Observation of ulcers was not done systematically after 90-day follow-up because it was not a part of the original protocol. Thus, data on healing within 140 days were missing for 2 participants.

Deviations in standard treatment and several patient and ulcer characteristics may affect healing, eg comorbidities, age, sex, distal blood perfusion, baseline wound size, and ulcer location.^27,30-33 In a future RCT, randomization will adjust to participant heterogeneity to some extent. Additional limitations were that patient acceptability to randomization and recruitment from more than 1 center was not assessed.

Conclusion

There were no patient-reported harmful effects and no adverse events with probable relation to inforatio technique. Patient acceptability, staff acceptability, and participant adherence was promising. Thus, a larger clinical trial for evaluating the clinical effect of inforatio technique is considered feasible to conduct.

Healing during a 140-day follow-up will be a suitable primary endpoint for measuring clinical effect while the change in ulcer area can be a surrogate measure. For a sample size calculation of a future RCT, we suggest that the proportion of healing is set at 60% for the intervention group that receives inforatio technique.

Based on the results of the feasibility trial, the following amendments of protocol can improve the assessment of clinical effect in a future RCT: (1) recruitment from multiple centers; (2) an upper limit for wound duration as an eligibility criterion; (3) a follow-up that is longer than 90 days; (4) routine delivery of written instructions on wound care at home; (5) information to eligible patients about participant benefits experienced from the feasibility trial; and (6) more frequent application of inforatio technique during follow-up.

Supplemental Material

sj-doc-1-ijl-10.1177_15347346211002364 - Supplemental material for Treatment of Diabetic Foot Ulcers With Inforatio Technique to Promote Wound Healing: A Feasibility Trial

Supplemental material, sj-doc-1-ijl-10.1177_15347346211002364 for Treatment of Diabetic Foot Ulcers With Inforatio Technique to Promote Wound Healing: A Feasibility Trial by Sahar Moeini, Hans Gottlieb, Tue S. Jørgensen, Malene R. B. Larsen and Stig Brorson in The International Journal of Lower Extremity Wounds

Footnotes

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Steno Diabetes Center Sjaelland. and Copenhagen University Research Promotion Fund for Region Zealand

Supplemental material

Supplemental material for this article is available online.

ORCID iDs

Sahar Moeini

Stig Brorson

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