Nearly half of patients receiving an experimental wound procedure alongside standard care achieved complete ulcer closure within 20 weeks, compared with just over one-quarter receiving standard care alone. The findings are promising, but larger trials are needed.
Key Takeaways
- In a randomized clinical trial involving 100 patients with diabetic foot ulcers, 49.0% of those receiving the inforatio technique plus standard care achieved complete wound closure within 20 weeks, compared with 27.5% receiving standard care alone.
- The absolute improvement was 21.5 percentage points, equivalent to approximately 22 additional healed ulcers per 100 patients treated under similar conditions.
- The procedure uses a sterile 2-mm biopsy punch costing approximately $2.50 and takes an estimated 1 to 5 minutes to perform. This is the instrument cost, not the total cost of clinical treatment.
- Ulcer-related complications were less common in the intervention group, but the trial did not establish a statistically significant reduction in serious events such as amputation, hospitalization, or death.
- The technique remains investigational and was tested only in selected patients with noninfected, superficial diabetic foot ulcers. It must not be attempted at home.
Introduction
In a randomized trial of 100 patients, 49% receiving the inforatio technique plus standard care achieved diabetic foot ulcer closure within 20 weeks, compared with 27.5% receiving standard care alone.
Diabetic foot ulcers are among the most difficult complications of diabetes to manage. Even with specialized wound care, some ulcers remain open for months, increasing the risk of infection, hospitalization, and amputation.
A randomized clinical trial published November 9, 2026, in JAMA Network Open suggests that a brief, inexpensive procedure could improve healing for certain patients.
The technique, called inforatio, involves making small, controlled incisions in the tissue of an existing ulcer using a sterile biopsy punch. Researchers tested whether adding the procedure to established wound care would help more ulcers close.
After 20 weeks, 24 of 49 patients receiving the technique had achieved complete ulcer closure, compared with 14 of 51 patients receiving standard care alone.
The difference is substantial for a condition in which healing can be slow and unpredictable. However, the study was relatively small, and its findings apply to a carefully selected group of patients rather than all diabetic foot wounds.
What the Study Examined
Researchers led by Sahar Moeini conducted the trial at four specialized wound care outpatient clinics in Denmark between February 2022 and December 2024. Medical-record follow-up continued into August 2025.
The investigators screened 695 patients. Of these, 549 were considered ineligible before treatment, and another 45 eligible patients declined participation.
A total of 101 people were randomized. One person assigned to the intervention group was subsequently found not to have diabetes and was excluded before receiving trial treatment.
The primary analysis therefore included 100 patients, with 49 assigned to inforatio plus standard care and 51 to standard care alone.
Participants had a mean age of 64.4 years. Eighty-five were men and 15 were women.
Most had type 2 diabetes: 39 of 49 patients in the intervention group and 44 of 51 in the control group.
Eligible participants had noninfected Wagner grade 1 diabetic foot ulcers that had been present for at least six weeks. These were superficial ulcers without the deeper tissue involvement characteristic of more advanced wound grades.
The researchers excluded patients with conditions including active ulcer infection, underlying bone infection, gangrene, critical limb ischemia, and certain other serious medical problems.
The findings were reported by Moeini et al. (2026).
How the Inforatio Technique Works
All participants received established diabetic foot ulcer care from multidisciplinary clinical teams.
This included removal of dead or unhealthy tissue, management of surrounding calluses, appropriate dressings, pressure relief through off-loading, patient education, and compression therapy when indicated.
Patients in the intervention group received an additional procedure at approximately three-week intervals during the first 12 weeks, for up to five treatment visits.
After routine wound debridement, the clinician used a sterile 2-mm biopsy punch to make small incisions in the ulcer bed near its edges.
The incisions were spaced approximately 3 to 5 mm apart. Their depth was adjusted to the available healthy granulation tissue, with a maximum depth of 3.5 mm.
No tissue was removed.
The procedure was avoided in areas where the tissue was too thin to protect underlying bone, tendons, or joints. Treatment was stopped if the wound developed infection, necrosis, deeper tissue involvement, or other specified complications.
According to the researchers, the biopsy punch costs approximately US $2.50, and the procedure takes 1 to 5 minutes, depending on wound size and the time needed to control bleeding.
Those figures describe the disposable instrument and procedure time. They do not include staffing, dressings, clinical assessment, follow-up visits, or the overall cost of care.
The researchers developed the technique after observing that tissue near sites where small biopsy samples had previously been taken appeared to show increased granulation and epithelial growth.
They proposed that carefully controlled tissue injury might stimulate healing processes in a chronic wound.
That biological explanation remains a hypothesis. The trial measured clinical outcomes, not the cellular mechanisms responsible for healing.
What Researchers Found
Nearly Half the Ulcers Closed With the Added Procedure
The primary outcome was complete ulcer closure within 20 weeks.
Closure required full epithelialization, meaning the wound surface had become covered with new skin, without discharge.
Two wound care nurses who did not know which treatment patients had received independently reviewed photographs to determine whether ulcers had closed. Disagreements were resolved by consensus.
The results showed a clear difference between groups.
| Outcome within 20 weeks | Inforatio plus standard care | Standard care alone |
|---|---|---|
| Patients analyzed | 49 | 51 |
| Ulcers completely closed | 24 | 14 |
| Closure proportion | 49.0% | 27.5% |
| Ulcers not meeting closure outcome | 25 | 37 |
The absolute difference in closure was 21.5 percentage points, with a 95% confidence interval of 2.9 to 40.1 percentage points.
The associated P value was .03.
In practical terms, the observed results correspond to approximately 22 additional ulcer closures for every 100 patients receiving the added procedure rather than standard care alone, assuming similar patients and treatment conditions.
The wide confidence interval is important. Although the trial detected a statistically significant benefit, the exact size of that benefit remains uncertain.
What the Adjusted Statistics Mean
The investigators also performed an adjusted statistical analysis to account for baseline characteristics that could influence ulcer healing.
The model included ulcer size, ulcer duration, whether the ulcer was located on the sole of the foot, glycated hemoglobin (HbA1c), and whether a patient had at least four conditions from a predefined list of medical comorbidities. The analysis also accounted for differences between participating treatment centers.
After adjustment, the odds ratio for complete ulcer closure was 3.01, with a 95% confidence interval of 1.20 to 7.58 and a P value of .02.
This means the estimated odds of complete closure were approximately three times as high in the intervention group after accounting for these factors.
It does not mean patients were three times as likely to heal. Odds and probabilities are different statistical measures, particularly when the outcome is relatively common.
The more intuitive comparison is the observed proportion of ulcers achieving closure: 49.0% with inforatio plus standard care versus 27.5% with standard care alone.
The unadjusted relative risk was 1.78, with a 95% confidence interval of 1.05 to 3.03. This corresponds to a 78% higher observed probability of closure in the intervention group.
All reported sensitivity analyses favored inforatio, including an analysis that retained the mistakenly randomized ineligible patient.
The trial had no missing primary outcome data, strengthening confidence in the comparison.
Nevertheless, the wide confidence intervals indicate uncertainty about the precise magnitude of the treatment benefit.
Did the Procedure Make Wounds Heal Faster?
The study found that more ulcers healed, but it did not demonstrate that those that healed did so faster.
Among patients whose ulcers closed, the mean time to closure was 75 days in the inforatio group and 71 days in the standard-care group.
The standard deviations were 35 days in both groups.
These descriptive figures should not be interpreted as evidence that standard care produces faster healing. They concern only the patients whose ulcers closed and do not provide a randomized comparison of time to healing across all participants.
The trial’s primary finding was an improvement in the proportion of ulcers achieving closure within 20 weeks.
What the Trial Revealed About Complications
The investigators tracked two groups of safety outcomes: complications related to the target ulcer and a separate composite of serious adverse events.
Fewer Patients Experienced Ulcer-Related Problems
At least one target ulcer-related adverse event occurred in 16 of 49 patients receiving inforatio, compared with 30 of 51 receiving standard care alone.
That represents 32.7% in the intervention group and 58.8% in the control group, an absolute difference of 26.1 percentage points.
The reported relative risk was 0.56, with a 95% confidence interval of 0.35 to 0.88 and a P value of .02.
This corresponds to a 44% lower observed relative risk of experiencing at least one event in the predefined composite.
However, the analysis was exploratory and was not adjusted for multiple statistical comparisons.
Furthermore, follow-up for target ulcer-related complications ended when an ulcer healed or the patient underwent amputation. Patients therefore had different periods during which events could be recorded.
These factors limit how confidently the difference can be attributed to the procedure.
A Closer Look at Specific Complications
The paper provides a detailed breakdown of complications within 20 weeks.
| Reported event | Inforatio (49 patients) | Standard care (51 patients) |
|---|---|---|
| Ulcer infection | 9 (18.4%) | 16 (31.4%) |
| Increase in ulcer size | 3 (6.1%) | 12 (23.5%) |
| Underlying bone infection | 4 (8.2%) | 8 (15.7%) |
| Exposed bone, tendon, or joint | 8 (16.3%) | 7 (13.7%) |
| Surgical wound revision | 4 (8.2%) | 3 (5.9%) |
| Target ulcer-related hospitalization | 5 (10.2%) | 9 (17.6%) |
These categories overlap because one patient could experience multiple complications.
The table shows why the overall safety result requires a nuanced interpretation.
Some events, including infection and wound enlargement, were less frequent in the intervention group. Others, including exposed deeper structures and surgical revision, were numerically more frequent.
The trial was not designed to establish reliable treatment effects for each individual complication.
Serious Events Were Not Significantly Reduced
The predefined serious adverse event composite included target ulcer-related hospitalization, amputation at any level of the affected limb, and death from any cause.
At least one serious event occurred in 7 of 49 patients receiving inforatio (14.3%) and 13 of 51 patients receiving standard care (25.5%).
The relative risk was 0.56, with a 95% confidence interval of 0.24 to 1.29 and a P value of .25.
Because the confidence interval included 1.00 and the P value was above .05, the difference was not statistically significant.
The study therefore does not establish that inforatio reduces amputations, serious complications, or deaths.
The researchers reported no harmful events that they or the clinical staff considered directly related to the procedure, and patients did not report such events. However, the sample was too small to rule out uncommon harms.
What Happened During One-Year Follow-Up?
The investigators also reviewed medical records for amputations and deaths within one year of enrollment.
Six patients in the intervention group underwent an amputation of the target limb, compared with 12 patients in the control group.
In the intervention group, two amputations were below the ankle and four were above it.
In the control group, eight were below the ankle and four were above it.
Four patients in the intervention group died during the year, compared with five in the control group.
These figures are worth reporting because diabetic foot ulcers can have serious long-term consequences.
However, the paper did not establish statistically significant differences in one-year amputation or mortality outcomes.
The numerical differences should not be presented as proof that the procedure prevents limb loss or improves survival.
Did Patients Feel Better?
Despite the improvement in ulcer closure, the trial did not find statistically significant differences in reported quality of life.
Researchers used two questionnaires.
The first measured general self-rated health on a scale from 0 to 100, with higher scores representing better health.
The second assessed quality of life specifically related to chronic wounds, with higher scores indicating worse wound-related quality of life.
For general self-rated health, the average change was zero points in the intervention group and an increase of two points in the control group.
The adjusted between-group difference was −1 point, with a 95% confidence interval of −8 to 6 and a P value of .85.
For wound-related quality of life, the adjusted difference was −0.3 points, with a 95% confidence interval of −0.8 to 0.1 and a P value of .17.
Neither comparison was statistically significant.
The quality-of-life analyses included 96 and 98 patients, respectively, because some final questionnaire data were missing.
These findings do not mean that ulcer healing has no effect on quality of life. Rather, this relatively small trial did not demonstrate a measurable advantage on the questionnaires used during its follow-up period.
How the Results Compare With Earlier Research
The new trial builds on a small feasibility study conducted by the same research group.
That earlier investigation involved 12 patients and helped establish whether the procedure could be performed and studied in a larger randomized trial (Moeini et al., 2023).
The researchers initially expected approximately 60% of ulcers in the intervention group to close within 20 weeks, based on the feasibility work.
The actual closure proportion was lower, at 49.0%, but still significantly exceeded the 27.5% observed with standard care.
The control group’s result was close to the approximately 30% closure rate the investigators used when planning the trial.
That estimate came from a systematic review of healing among patients receiving standard treatment for diabetic neuropathic foot ulcers (Margolis et al., 1999).
The comparison is useful, although healing rates vary substantially across studies depending on ulcer severity, patient characteristics, care practices, and follow-up duration.
The distinctive contribution of the new study is that it tested a low-cost, clinician-performed addition to standard wound care in a randomized design.
Why the Results Are Promising but Not Definitive
Several aspects of the trial strengthen its findings.
Randomization reduced the risk that patient characteristics systematically determined treatment assignment.
The study was conducted across four clinics rather than a single center.
All 100 eligible patients had primary outcome data, and adherence to the protocol was high.
Most importantly, ulcer closure was evaluated by nurses blinded to treatment allocation.
Nevertheless, important uncertainties remain.
Small Sample and Wide Confidence Intervals
Although the study met its planned enrollment target, 100 patients is a relatively small sample for evaluating a new wound treatment.
The adjusted odds ratio confidence interval ranged from 1.20 to 7.58, indicating considerable uncertainty about the magnitude of the benefit.
Treatment Could Not Be Blinded
Patients and treating clinicians knew which treatment had been assigned.
The researchers acknowledged that this knowledge could have influenced other aspects of care, including adherence to off-loading devices.
Blinded photographic review reduced the risk of bias in outcome assessment but could not eliminate all effects of the open-label design.
Baseline Differences Between Groups
Some medical conditions were unevenly distributed.
For example, congestive heart failure was present in 22.4% of the intervention group and 31.4% of the control group.
Chronic obstructive pulmonary disease was also more common in the control group.
Conversely, diabetic retinopathy was more common in the intervention group, and ulcers had generally been present longer.
The statistical model accounted for whether patients had at least four predefined comorbidities, but it did not separately adjust for each individual condition.
Small trials can remain vulnerable to imbalances that affect outcomes.
The Primary Statistical Model Was Modified During the Trial
The researchers reported that the primary statistical model was modified after five participants had completed their 20-week follow-up.
Following peer-review recommendations, the investigators added adjustments for selected baseline characteristics that could influence wound healing.
The original prespecified model was retained as a sensitivity analysis, and the reported sensitivity analyses continued to favor the inforatio technique.
This provides some reassurance that the main finding was not dependent on a single statistical approach.
Nevertheless, changes to an analysis plan after a trial has begun are relevant when assessing methodological rigor. The timing and rationale for the modification should be considered alongside the trial’s other strengths and limitations.
The Results Apply to a Narrow Patient Population
The participants had noninfected Wagner grade 1 ulcers, and 85% were men.
Patients with infected wounds, underlying osteomyelitis, gangrene, or critical limb ischemia were excluded.
The findings cannot automatically be applied to more severe diabetic foot wounds or to patients with different clinical characteristics.
The authors also noted that some patients whose ulcers were already responding well to routine treatment may have been less likely to enter the trial.
This could affect how representative the participants were of patients seen in everyday wound clinics.
More Research Is Needed on Cost and Safety
Although the disposable biopsy punch is inexpensive, the trial did not provide a full cost-effectiveness analysis.
It also did not establish the procedure’s safety across larger populations, different clinical settings, or repeated use outside specialized wound care teams.
The researchers called for larger clinical studies examining effectiveness and cost-effectiveness in routine practice.
What Patients With Diabetic Foot Ulcers Should Know
The inforatio technique is an investigational addition to standard diabetic foot ulcer care. Although this randomized trial found encouraging results, larger studies are needed before its effectiveness, safety, and role in routine treatment can be established.
The procedure was performed by a trained clinician after professional wound assessment and debridement. It involved controlled incisions made with a sterile instrument under specific safety precautions.
Patients should never attempt this procedure themselves or use a biopsy punch or other sharp instrument to make cuts in a diabetic foot wound.
Established diabetic foot ulcer care remains essential. Treatment generally includes professional wound assessment, removal of unhealthy tissue when appropriate, pressure relief through off-loading, suitable dressings, infection monitoring, and management of diabetes and circulation problems.
These measures are consistent with the International Working Group on the Diabetic Foot’s practical guidelines (Schaper et al., 2024).
Patients should seek prompt medical assessment if a wound becomes red, swollen, warm, increasingly painful, foul-smelling, or develops new drainage. Fever, spreading redness, blackened tissue, or rapid deterioration may require urgent evaluation. People with diabetic neuropathy may develop serious infections without experiencing substantial pain.
Patients interested in new wound-healing treatments can discuss available options with their diabetes or specialist wound care team.
For now, inforatio should be understood as a promising technique under clinical investigation, not a replacement for established diabetic foot ulcer treatment.
Final Thoughts
A randomized clinical trial involving 100 patients found that adding the inforatio technique to standard care increased complete diabetic foot ulcer closure from 27.5% to 49.0% within 20 weeks.
The 21.5-percentage-point absolute improvement is the study’s most important finding.
The procedure’s low-cost instrument and short treatment time make it an interesting candidate for further research, particularly in settings where expensive wound therapies are difficult to access.
The investigators also observed fewer ulcer-related adverse events, but the trial did not establish reductions in serious complications, amputations, or deaths. Nor did it demonstrate improved quality of life or faster healing among ulcers that closed.
Larger studies are needed to confirm the benefit, identify which patients are most likely to respond, and establish whether the procedure is safe and cost-effective in routine practice.
For now, inforatio is a promising clinician-performed adjunct for selected diabetic foot ulcers, not a proven treatment for every diabetic wound.
Funding and Disclosures
The trial received support from the Vissing Foundation, Steno Diabetes Center Zealand, Fonden af 17-12-1981, Region Zealand and the University of Copenhagen, Kong Christian den Tiendes Fond, the A.P. Moeller Foundation, and the Sawmill Owner Jeppe Juhl and wife Ovita Juhls Memorial Fund.
The authors stated that the sponsors had no role in study design, conduct, data collection, analysis, interpretation, manuscript preparation, or the decision to submit the findings for publication.
The authors reported no competing interests.
The trial was registered at ClinicalTrials.gov as NCT05189470.
References
Margolis, D. J., Kantor, J., & Berlin, J. A. (1999). Healing of diabetic neuropathic foot ulcers receiving standard treatment: A meta-analysis. Diabetes Care, 22(5), 692–695. https://doi.org/10.2337/diacare.22.5.692
Moeini, S., Gottlieb, H., Jørgensen, T. S., Larsen, M. R. B., & Brorson, S. (2023). Treatment of diabetic foot ulcers with inforatio technique to promote wound healing: A feasibility trial. International Journal of Lower Extremity Wounds, 22(2), 241–250. https://doi.org/10.1177/15347346211002364
Moeini, S., Gottlieb, H., Jørgensen, T. S., Larsen, M. R. B., & Brorson, S. (2026). Inforatio technique and foot ulcer closure among patients with diabetes: A randomized clinical trial. JAMA Network Open, 9(11), e2642733. https://doi.org/10.1001/jamanetworkopen.2026.42733
Schaper, N. C., van Netten, J. J., Apelqvist, J., Bus, S. A., Hinchliffe, R. J., Lipsky, B. A., & IWGDF Editorial Board. (2024). Practical guidelines on the prevention and management of diabetes-related foot disease (IWGDF 2023 update). Diabetes/Metabolism Research and Reviews, 40(3), e3657. https://doi.org/10.1002/dmrr.3657
