Diabetic Foot Ulcer
Conditions
Keywords
topical chlorhexidine, prevention, clinical trial
Brief summary
Foot complications are among the most serious and costly complications of diabetes. People with diabetes have a 10-fold increased risk for a leg or foot amputation compared to those that do not have diabetes. Amputation of all or part of foot is usually preceded by a foot ulcer, which became infected. This is a clinical trial to test the effectiveness of a topical antiseptic, chlorhexidine, for daily foot cleaning on the occurrence of diabetic foot ulcers in Veterans at high risk of a diabetic foot ulcer.
Detailed description
Population: Up to 200 Veterans at high risk of a diabetic foot ulcer Site: VA Maryland Health Care System (VAMHCS) Study Duration: Approximately 5 years Study Design: Randomized double-blind clinical trial comparing a) a daily foot care regimen with cloths containing 2% chlorhexidine to b) a daily foot care regimen with cloths not containing 2% chlorhexidine Objectives: Primary: To determine if chlorhexidine reduces the occurrence of foot complications including chronic foot ulcer, foot infection or foot amputation. Secondary: To determine if chlorhexidine increases antibiotic resistance among bacterial pathogens on feet. Exploratory: To describe changes in the microbiota of the feet with chlorhexidine and foot complications Treatment Regimens: 2% Chlorhexidine Gluconate Cloths versus Bath Cloths Route of Administration: Topical application on the feet Dose and Interval: 1 cloth daily Duration of Participant's Participation: Up to 13 months
Interventions
DRUGChlorhexidine
Participants randomized to the intervention will wash their feet using 2% CHLORHEXIDINE GLUCONATE CLOTHS to wipe down their feet each day and then apply supplied chlorhexidine-compatible over-the-counter moisturizer.
DRUGPlacebo
Participants randomized to the placebo will wash their feet using COMFORT BATH CLOTHS to wipe down their feet each day and then apply supplied chlorhexidine-compatible over-the-counter moisturizer.
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
This is a single center, randomized, double blind (participant, outcome assessor), parallel group clinical trial comparing daily foot care with cloths containing 2% chlorhexidine compared to daily foot care with cloths not containing chlorhexidine.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults \>=18 years * Clinical diagnosis of diabetes * At high risk for a new diabetic foot ulcer due to: 1)Past history of diabetic foot ulcer or 2)Past history of major foot surgery including partial foot amputation or 3)Past history of major foot infection or 4)Neuropathy and onychomycosis and hemoglobin A1C \>8% or 5)Neuropathy and peripheral vascular disease or 6)Dialysis or 7)Past history of Charcot foot or 8)Past history of peripheral vascular surgery or angiography with stent * Two feet (can have amputation of part of the foot) * At least one foot without a foot ulcer * Permanent mailing address suitable for provision of specimen collection materials and telephone suitable for monthly follow-up * Able to give written informed consent
Exclusion criteria
* Amputation of the foot planned to treat current foot ulcer or wound * Current foot infection * Use of topical chlorhexidine on feet 7 days prior to randomization * History of an allergic reaction to chlorhexidine * Unable to use wipes for foot care * Inability to walk * Life expectancy less than 12 months * Plans to move out of the area in the next 13 months * Requires equivalent of institutional care (e.g. nursing home) * Any other criteria which, in the investigator's opinion, would compromise the safety of the study, the ability of a subject to participate, or the results of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to New Foot Complication Among All Randomized Participants | 12 months | Time in days to new foot complication (analyzed with the use of unadjusted Cox proportional-hazard models to identify time to new foot complication; the results we are reporting are number of participants who developed a new foot complication in the 12 months post randomization). A new foot complication is defined as either 1) a new chronic (present 28 days from initial diagnosis) foot ulcer or wound or 2) a moderate or severe foot infection (as defined by IDSA Diabetic Foot Infection Severity classification: Table 2) not from an existing ulcer or 3) a foot amputation for a new ulcer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Susceptibility to Chlorhexidine Among Bacterial Pathogens on the Feet | 4 weeks after stopping the intervention (approximately 13 months after randomization) | Susceptibility to chlorhexidine among bacterial pathogens on the feet. Chlorhexidine minimum inhibitory concentration (MIC) values were normalized across pathogens by subtracting the median MIC value (MIC50) from the literature for each pathogen from the observed MIC value on a log2() scale. The results we are reporting are the mean normalized MIC values and the Wilcoxon Rank Sum test comparing the difference in distribution of normalized MIC values. Effect size is expressed in means as this is more sensitive to group differences than the median. The possible range for the normalized observed MIC values on a log2() scale is from -8 to 8 with a higher value indicating that the pathogens collected were more resistant to chlorhexidine as compared to the median MIC values reported in the literature. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Time to New Foot Complication Among Participants With a Healed Foot Complication at Randomization. | 12 months | Time in days to new foot complication (analyzed with the use of unadjusted Cox proportional-hazard models to identify time to new foot complication; the results we are reporting are number of participants who developed a new foot complication in the 12 months post randomization). A new foot complication is defined as either 1) a new chronic (present 28 days from initial diagnosis) foot ulcer or wound or 2) a moderate or severe foot infection (as defined by IDSA Diabetic Foot Infection Severity classification: Table 2) not from an existing ulcer or 3) a foot amputation for a new ulcer. |
Countries
United States
Participant flow
Recruitment details
Recruitment occurred between January 2019 and December 2021 in the Baltimore VA Medical Center.
Participants by arm
| Arm | Count |
|---|---|
| Chlorhexidine Participants randomized to the intervention will wash their feet using 2% CHLORHEXIDINE GLUCONATE CLOTHS to wipe down their feet each day and then apply supplied chlorhexidine-compatible over-the-counter moisturizer.
Chlorhexidine: Participants randomized to the intervention will wash their feet using 2% CHLORHEXIDINE GLUCONATE CLOTHS to wipe down their feet each day and then apply supplied chlorhexidine-compatible over-the-counter moisturizer. | 88 |
| Placebo Participants randomized to the placebo will wash their feet using COMFORT BATH CLOTHS to wipe down their feet each day and then apply supplied chlorhexidine-compatible over-the-counter moisturizer.
Placebo: Participants randomized to the placebo will wash their feet using COMFORT BATH CLOTHS to wipe down their feet each day and then apply supplied chlorhexidine-compatible over-the-counter moisturizer. | 87 |
| Total | 175 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 1 |
Baseline characteristics
| Characteristic | Chlorhexidine | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 67 years STANDARD_DEVIATION 8 | 68 years STANDARD_DEVIATION 10 | 68 years STANDARD_DEVIATION 9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 87 Participants | 87 Participants | 174 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Healed foot complication | 48 Participants | 43 Participants | 91 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 60 Participants | 57 Participants | 117 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 25 Participants | 28 Participants | 53 Participants |
| Region of Enrollment United States | 88 Participants | 87 Participants | 175 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 85 Participants | 85 Participants | 170 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 88 | 1 / 87 |
| other Total, other adverse events | 1 / 88 | 2 / 87 |
| serious Total, serious adverse events | 23 / 88 | 17 / 87 |
Outcome results
Primary
Time to New Foot Complication Among All Randomized Participants
Time in days to new foot complication (analyzed with the use of unadjusted Cox proportional-hazard models to identify time to new foot complication; the results we are reporting are number of participants who developed a new foot complication in the 12 months post randomization). A new foot complication is defined as either 1) a new chronic (present 28 days from initial diagnosis) foot ulcer or wound or 2) a moderate or severe foot infection (as defined by IDSA Diabetic Foot Infection Severity classification: Table 2) not from an existing ulcer or 3) a foot amputation for a new ulcer.
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chlorhexidine | Time to New Foot Complication Among All Randomized Participants | 12 Participants |
| Placebo | Time to New Foot Complication Among All Randomized Participants | 14 Participants |
95% CI: [0.39, 1.8]
Secondary
Susceptibility to Chlorhexidine Among Bacterial Pathogens on the Feet
Susceptibility to chlorhexidine among bacterial pathogens on the feet. Chlorhexidine minimum inhibitory concentration (MIC) values were normalized across pathogens by subtracting the median MIC value (MIC50) from the literature for each pathogen from the observed MIC value on a log2() scale. The results we are reporting are the mean normalized MIC values and the Wilcoxon Rank Sum test comparing the difference in distribution of normalized MIC values. Effect size is expressed in means as this is more sensitive to group differences than the median. The possible range for the normalized observed MIC values on a log2() scale is from -8 to 8 with a higher value indicating that the pathogens collected were more resistant to chlorhexidine as compared to the median MIC values reported in the literature.
Time frame: 4 weeks after stopping the intervention (approximately 13 months after randomization)
Population: Participants must have at least one bacterial pathogen on their feet to be included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chlorhexidine | Susceptibility to Chlorhexidine Among Bacterial Pathogens on the Feet | -1.83 units on a scale | Standard Deviation 1.44 |
| Placebo | Susceptibility to Chlorhexidine Among Bacterial Pathogens on the Feet | -1.88 units on a scale | Standard Deviation 1.52 |
p-value: 0.97Wilcoxon (Mann-Whitney)
Other Pre-specified
Time to New Foot Complication Among Participants With a Healed Foot Complication at Randomization.
Time in days to new foot complication (analyzed with the use of unadjusted Cox proportional-hazard models to identify time to new foot complication; the results we are reporting are number of participants who developed a new foot complication in the 12 months post randomization). A new foot complication is defined as either 1) a new chronic (present 28 days from initial diagnosis) foot ulcer or wound or 2) a moderate or severe foot infection (as defined by IDSA Diabetic Foot Infection Severity classification: Table 2) not from an existing ulcer or 3) a foot amputation for a new ulcer.
Time frame: 12 months
Population: Participants must have had a healed foot complication at randomization to be included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chlorhexidine | Time to New Foot Complication Among Participants With a Healed Foot Complication at Randomization. | 11 Participants |
| Placebo | Time to New Foot Complication Among Participants With a Healed Foot Complication at Randomization. | 12 Participants |
95% CI: [0.34, 1.77]