Two randomized controlled trials recently tested methods for wound healing in patients with diabetic foot ulcers.
The first study, a randomized, double-blind, placebo-controlled trial, was conducted in Iran and involved 60 patients who were 40 to 85 years of age and had grade 3 diabetic foot ulcers. Patients were randomly divided into two groups to receive either a probiotic supplement (a capsule containing Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus fermentum, and Bifidobacterium bifidum) or placebo each day for 12 weeks. Each group included 30 patients. The main outcomes were wound healing and glucose homeostasis parameters; secondary outcomes were lipid profiles, biomarkers of inflammation, and oxidative stress. The study results were published online Dec. 21, 2017, by Diabetes Metabolism Research and Reviews.
Fifty-nine patients completed the trial, with one patient in the placebo group withdrawing for personal reasons, but all patients were included in the final intention-to-treat analyses. After 12 weeks, patients in the intervention group had significantly reduced ulcer length (change, −1.3 ± 0.9 cm vs. −0.8 ± 0.7 cm; P=0.01), width (change, −1.1 ± 0.7 cm vs. −0.7 ± 0.7 cm; P=0.02), and depth (change, −0.5 ± 0.3 cm vs. −0.3 ± 0.3 cm; P=0.02) versus the placebo group. In addition, those in the intervention group had significant reductions in fasting plasma glucose levels (P=0.01), serum insulin levels (P=0.03), and HbA1c levels (P=0.003) and a significant increase in quantitative insulin sensitivity check index (0.01 ± 0.01 vs. −0.01 ± 0.02; P=0.003). Serum total cholesterol level (P=0.04), high-sensitivity C-reactive protein level (P=0.02), and plasma malondialdehyde level (P=0.001) also decreased significantly in the intervention group versus placebo, while plasma nitric oxide (P=0.01) and total antioxidant capacity concentration (P<0.001) showed a significant increase.
The authors noted that they did not measure fecal bacteria loads before and after the intervention or characterization of the microbiome before, during, and after therapy, among other limitations. However, they concluded that 12 weeks of probiotic supplements had beneficial effects on ulcer size, glucose metabolism, and other factors in patients with diabetic foot ulcers but did not appear to affect inflammation or oxidative stress, among other variables. They called for future studies to examine tailoring probiotic therapy to individual patients, as well as mechanisms of action and time needed for healing.
The second study, an industry-funded randomized, double-blind clinical trial of 43 hospitals in Europe that had specialized diabetic foot clinics, included inpatients or outpatients who were at least 18 years of age and had a noninfected neuroischemic diabetic foot ulcer that measured greater than 1 cm2 and was grade IC or IIC according to the University of Texas Wound Classification system. Patients were excluded if they had a severe illness that might affect trial participation or if they had had a surgical revascularization procedure in the month before study entry.
Between March 21, 2013, and March 31, 2016, a computer-generated randomization procedure was used to assign patients to treatment with a sucrose octasulfate wound dressing or a control dressing without sucrose octasulfate for a 20-week period. Other than the dressing, groups received the same standard of care during a two-week screening period before the study and during the study itself. Patients used preapproved offloading devices and were told that they should wear them at all times. Assessments were done for all patients two weeks after randomization and then monthly until week 20 or until the wound closed. The primary outcome was the proportion of patients whose wounds were closed at week 20. The results of the study, which was funded by Laboratoires Urgo Medical, were published online Dec. 20, 2017, by Lancet Diabetes and Endocrinology.
Overall, 240 patients were randomly assigned, 126 to the treatment group and 114 to the control group. The median duration of treatment was 135 days in the control group and 115 days in the treatment group. At 20 weeks, 60 patients in the treatment group had wound closure versus 34 patients in the control group (48% vs. 30%; adjusted odds ratio, 2.60; P=0.002). Estimated mean time to closure was 60 days (95% CI, 47 to 75 days) longer in the control group versus the treatment group. The most common adverse event in both groups was wound infection (33 infections in 25 patients in the treatment group and 36 infections in 32 patients in the control group; 20% and 28%, respectively). One patient in the treatment group and two patients in the control group had minor amputations involving the target foot that did not affect the wound site (1% and 2%, respectively). Three patients in the treatment group and four patients in the control group died (2% and 4%, respectively), but none of the deaths were considered to be related to wounds or to wound treatment.
The authors noted that offloading devices used during the study differed across hospitals and that their study did not examine cost-effectiveness. However, they concluded that treatment with a sucrose octasulfate dressing improved wound closure over a 20-week period in patients with neuroischemic diabetic foot ulcers versus a control dressing. “A sucrose octasulfate dressing is effective and safe, and its use is easy to implement by all health-care professionals,” the authors wrote. “This dressing could form an important part of modern multidisciplinary management of neuroischaemic diabetic foot ulcers.”
An accompanying comment noted that the study's generalizability may be limited, since the definition of neuroischemic wounds is not clear and since only a few patients were recruited at each of the included clinics, suggesting that the enrollment criteria excluded most patients. However, the comment author said that sucrose octasulfate dressings “seem to be a promising addition to our current treatment strategies for diabetic foot ulcers positioned away from the heel, which have not shown a significant reduction in area despite good offloading and other best practice treatments, and where patients also have peripheral arterial disease that is not being considered for vascular intervention.”