Topical Platelet-Derived Growth Factor in Diabetic Foot Ulcers
Topical Platelet-Derived Growth Factor in Diabetic Foot Ulcers
Demographic and wound characteristics of the patients are shown in Table 1. A total of 46 subjects were enrolled, and 23 were assigned randomly to each treatment group. The age, body mass index (BMI), A1c hemoglobin levels, current smoking status, and proportion of subjects taking insulin were comparable between the 2 groups. There was significantly higher mean ESR in the test group (32.3 ± 16.6 mm/hour vs 54.6 ± 24.5 mm/hour for control vs test, respectively; P = 0.004). In addition, the wound duration prior to treatment was longer in the test group (18.5 ± 22.2 compared to 9.8 ± 11.6 weeks for the control group, P = 0.11) although this did not achieve statistical significance.
Based on intention to treat, without excluding subjects who dropped out, there was no significant difference in healing rates at 4 months between patients in the control group and the test group (57% vs 52%, respectively; chi-square P = 0.77). Figure 2 shows the Kaplan-Meier curves of wound healing during 4 months of monitored therapy by the test group. No significant difference was observed in time to wound healing between the test and control groups (median time to healing: 97 vs 91 days, respectively, log-rank P = 0.70). Results from the separate regressions indicate that only 2 factors were significantly associated with longer time to wound healing, initial wound size (hazard ratio [HR] = 0.997, 95% confidence interval [CI]: 0.995–1.00, P = 0.028), and excessive drainage (HR = 0.346, 95% CI: 0.126–0.948, P = 0.039). A multifactor Cox PH regression model demonstrated that slower healing was associated with larger initial wound size (HR = 0.998, 95% CI: 0.996–1.00, P = 0.017) as well as excessive wound drainage, (HR = 0.370, 95% CI: 0.132–1.036, P = 0.059) though the latter did not achieve statistical significance.
(Enlarge Image)
Figure 2.
Kaplan-Meier plot showing proportion of ulcers remaining unhealed over time. test: treated with platelet derived growth factor; control: treated with placebo
During the course of the study, 8 subjects (3 in the test group and 5 in the control group) dropped out. One subject in the test group died unexpectedly of unrelated causes during the first week after randomization. The other 7 subjects dropped out due to anxiety (1), inability to tolerate the cast (1), job change (1), cast-related pain (2), inconvenience of the cast (1), and hospitalization for unrelated causes (1).
There were no other deaths during the treatment and follow-up intervals. If dropouts are excluded, 66% (25/38) of subjects who were treated with casting for 4 months experienced complete wound healing. Three subjects, 2 from the control group and 1 from the test group, who had partial wound healing during the first 4 months continued with casting and healed during the follow-up phase at 5, 6, and 9 months after randomization, respectively. When these 3 subjects are considered, complete healing of the study ulcers was observed in 74% (28/38) of subjects treated with cast therapy up to 9 months after study enrollment.
New cast-related ulcers, or cast burns, developed in areas of skin undamaged at study entry in 5 subjects. Three were in the test group and 2 in the control group. Three of these patients were successfully treated by continued casting with a second window cut out over the new ulcer until the cast burn healed. One patient developed a cast burn that never healed. Lastly, 1 patient healed his study wound over the fifth metatarsal head, but developed a cast burn over the midfoot, which eventually required transmetatarsal amputation.
Two other subjects enrolled in the study required amputation. The first was a patient in the control group whose wound worsened despite off-loading, which eventually required transmetatarsal amputation 6 months after enrollment. The other patient was in the test group. His wound never healed, and after casting was discontinued at 4 months, he developed infection requiring below-knee amputation at 14 months after enrollment.
Results
Demographic and Wound Characteristics
Demographic and wound characteristics of the patients are shown in Table 1. A total of 46 subjects were enrolled, and 23 were assigned randomly to each treatment group. The age, body mass index (BMI), A1c hemoglobin levels, current smoking status, and proportion of subjects taking insulin were comparable between the 2 groups. There was significantly higher mean ESR in the test group (32.3 ± 16.6 mm/hour vs 54.6 ± 24.5 mm/hour for control vs test, respectively; P = 0.004). In addition, the wound duration prior to treatment was longer in the test group (18.5 ± 22.2 compared to 9.8 ± 11.6 weeks for the control group, P = 0.11) although this did not achieve statistical significance.
Treatment Effect on Healing and Factors Related to Healing
Based on intention to treat, without excluding subjects who dropped out, there was no significant difference in healing rates at 4 months between patients in the control group and the test group (57% vs 52%, respectively; chi-square P = 0.77). Figure 2 shows the Kaplan-Meier curves of wound healing during 4 months of monitored therapy by the test group. No significant difference was observed in time to wound healing between the test and control groups (median time to healing: 97 vs 91 days, respectively, log-rank P = 0.70). Results from the separate regressions indicate that only 2 factors were significantly associated with longer time to wound healing, initial wound size (hazard ratio [HR] = 0.997, 95% confidence interval [CI]: 0.995–1.00, P = 0.028), and excessive drainage (HR = 0.346, 95% CI: 0.126–0.948, P = 0.039). A multifactor Cox PH regression model demonstrated that slower healing was associated with larger initial wound size (HR = 0.998, 95% CI: 0.996–1.00, P = 0.017) as well as excessive wound drainage, (HR = 0.370, 95% CI: 0.132–1.036, P = 0.059) though the latter did not achieve statistical significance.
(Enlarge Image)
Figure 2.
Kaplan-Meier plot showing proportion of ulcers remaining unhealed over time. test: treated with platelet derived growth factor; control: treated with placebo
Dropouts and Complications
During the course of the study, 8 subjects (3 in the test group and 5 in the control group) dropped out. One subject in the test group died unexpectedly of unrelated causes during the first week after randomization. The other 7 subjects dropped out due to anxiety (1), inability to tolerate the cast (1), job change (1), cast-related pain (2), inconvenience of the cast (1), and hospitalization for unrelated causes (1).
There were no other deaths during the treatment and follow-up intervals. If dropouts are excluded, 66% (25/38) of subjects who were treated with casting for 4 months experienced complete wound healing. Three subjects, 2 from the control group and 1 from the test group, who had partial wound healing during the first 4 months continued with casting and healed during the follow-up phase at 5, 6, and 9 months after randomization, respectively. When these 3 subjects are considered, complete healing of the study ulcers was observed in 74% (28/38) of subjects treated with cast therapy up to 9 months after study enrollment.
New cast-related ulcers, or cast burns, developed in areas of skin undamaged at study entry in 5 subjects. Three were in the test group and 2 in the control group. Three of these patients were successfully treated by continued casting with a second window cut out over the new ulcer until the cast burn healed. One patient developed a cast burn that never healed. Lastly, 1 patient healed his study wound over the fifth metatarsal head, but developed a cast burn over the midfoot, which eventually required transmetatarsal amputation.
Two other subjects enrolled in the study required amputation. The first was a patient in the control group whose wound worsened despite off-loading, which eventually required transmetatarsal amputation 6 months after enrollment. The other patient was in the test group. His wound never healed, and after casting was discontinued at 4 months, he developed infection requiring below-knee amputation at 14 months after enrollment.
Source...