Pirfenidone Clinical Study 4

A randomized crossover study to evaluate the effect of pirfenidone added to conventional treatment on noninfected diabetic foot ulcers, assessing the rate of complete wound closure and the change in ulcer size.

• Conventional treatment consisted of weekly ulcer cleansing with saline, debridement using a surgical blade, maintenance of a moist environment, and covering with sterile gauze. In addition, patients were instructed to perform daily cleansing with saline-moistened gauze and offload the affected extremity.
• Topical pirfenidone treatment consisted of applying pirfenidone over the ulcer twice a day.
• All patients completed a pretreatment phase of 7 days, receiving conventional treatment. After this week, participants were randomly assigned to one of the two groups.
• Group 1 received conventional treatment in combination with topical pirfenidone for the first eight weeks, and at the end of this period, they were switched to conventional treatment only for the remaining 8 weeks.
• Group 2 received conventional treatment only for the first 8 weeks, and at the end of this period, they were switched to conventional treatment in combination with topical pirfenidone for another 8 weeks.
• Patients were evaluated weekly during the 17 weeks at the diabetic foot clinic.
• The endpoints were complete ulcer healing and size reduction.

• Fifty-two percent of ulcers treated with pirfenidone healed before 8 weeks versus 14.3% treated with conventional treatment only (P = 0.025).
• Between 8 and 16 weeks, 30.8% ulcers that received pirfenidone healed versus 0% with conventional treatment (P = 0.081).
• By week 8, the reduction in ulcer size was 100% [73-100] with pirfenidone versus 57.5% with conventional treatment [28.9-74] (P = 0.011).
• By week 16, the reduction was 93% [42.7-100] with pirfenidone and 21.8% [8-77.5] with conventional treatment (P = 0.050).
• No serious adverse events were observed during the study in any treatment group.

Table 2: Healing of the ulcers

	Group 1	Group 2	P-value
Percentage of ulcers healed before 8 weeks	52.40%	14.30%	P = 0.025
Percentage of ulcers healed between 8 and 16 weeks	0%	30.80%	P = 0.081
Reduction in ulcer size by week 8	100%	57.50%	P = 0.011
Reduction in ulcer size by week 16	21.80%	93%	P = 0.050

The addition of topical pirfenidone to conventional treatment significantly improves the healing of chronic diabetic noninfected foot ulcers.