Efficacy of Plasma Rich in Growth Factors in Treating Diabetic Foot Ulcers with Peripheral Arterial Disease: A Randomized Controlled Trial

The primary objective of this randomized, controlled clinical trial is to evaluate the **efficacy** of Plasma Rich in Growth Factors (PRGF) in the treatment of foot ulcers in diabetic patients with peripheral arterial disease. The assessment focuses on the evolution of foot ulcer healing over a six-month period, utilizing the RESVECH 2.0 index as a measure of healing progress. This objective is clinically relevant as it addresses the need for effective treatments in managing foot ulcers, a common and serious complication in diabetic patients with peripheral arterial disease, which can lead to significant morbidity and healthcare costs.

The clinical trial focuses on evaluating the efficacy of **PRGF** in the healing of foot ulcers in diabetic patients with peripheral arterial disease. The study population includes both male and female participants aged 18 years and older, diagnosed with either type 1 or type 2 diabetes. Participants must have one or more ulcers below the malleoli, with sizes ranging from 1 to 25 cm², and must exhibit peripheral arterial disease. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants' general health status is characterized by the presence of diabetes and peripheral arterial disease, with specific criteria for ulcer size and severity of infection. Lifestyle considerations such as diet and physical activity are not specified. Key inclusion criteria include the absence of peripheral pulses, specific ankle and finger pressure measurements, and an ankle-brachial index within a defined range. The degree of infection must not exceed a certain level on the IDSA/IWGDF scale, and participants must be available for observation throughout the study period.

The clinical trial is designed as a **randomized**, **controlled**, and **double-blind** study to evaluate the efficacy of **Plasma Rich in Growth Factors (PRGF)** in the treatment of foot ulcers in diabetic patients with peripheral arterial disease. The trial aims to assess the healing of foot ulcers over a period of six months, with the primary endpoint being the evaluation of ulcer healing using the RESVECH 2.0 index. The study is categorized as a low-intervention trial and is expected to commence recruitment on May 6, 2024, with an estimated completion date of May 8, 2026.

Participants will be involved in the study for a maximum of six months, during which they will attend several study visits. The sequence of visits includes an initial **screening visit** to confirm eligibility based on criteria such as age, diabetes diagnosis, ulcer characteristics, and peripheral arterial disease indicators. Following successful screening, participants will be randomized to receive either the PRGF treatment or a conventional treatment. **Follow-up visits** will occur at baseline, three months, and six months to monitor ulcer healing, assess secondary endpoints such as changes in ulcer size, amputation risk, and quality of life, and to record any adverse events. The **end-of-study visit** will coincide with the six-month follow-up, where final assessments will be conducted.

Participants may be withdrawn from the study if they experience significant adverse events, fail to adhere to the study protocol, or if the investigator deems it necessary for their safety. The study will ensure that all participants provide informed consent and that their involvement is monitored throughout the trial duration. The use of PRGF, administered topically in gel form, will be evaluated for its potential to enhance ulcer healing compared to conventional treatments, with a maximum daily dose of 2 ml and a total dose not exceeding 32 ml over the treatment period.

The clinical trial involves the use of an **experimental medication** known as "Plasma Rich in Growth Factors" (PRGF), which is formulated as a **gel**. The active substance in this product is a **platelet concentrate**, also referred to as "Platelet Rich Plasma Human." This substance is derived from blood, classified as a structurally diverse substance. The gel is applied **topically** to the affected area. The maximum daily dose is 2 ml, with a total maximum dose of 32 ml over the course of the treatment. The treatment period is set for a maximum of six months. The product is manufactured by Biotechnology Institute I Mas D S.L. and is not a pediatric formulation.

In this trial, the experimental treatment is compared against a **conventional treatment** for foot ulcers in diabetic patients with peripheral arterial disease. The conventional treatment serves as the **comparator treatment** to evaluate the efficacy of PRGF. The study aims to assess the healing evolution of foot ulcers over a six-month period, using the RESVECH 2.0 index as a measure of efficacy. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the treatment protocol.

The efficacy of Plasma Rich in Growth Factors (PRGF) in the treatment of foot ulcers in diabetic patients with peripheral arterial disease will be assessed in a randomized, controlled clinical trial. The primary endpoint for evaluating efficacy is the assessment of ulcer healing using the RESVECH 2.0 index at six months. Secondary endpoints include changes in ulcer size at three and six months, frequency of ulcers with complete closure at these timepoints, and assessment of ulcer healing with the RESVECH 2.0 index at baseline and three months. Additional secondary endpoints involve the assessment of amputation risk using the WIfI scale, pain and quality of life measured by the EQ-5D-5L scale, and the cost of wound closure. The incidence and type of adverse events, presence of infection assessed with the IWGDF/IDSA classification, and frequency and type of deficiencies in medical devices used for PRGF preparation will also be evaluated. Biomarkers involved in tissue damage repair will be monitored to provide further insights into the treatment's efficacy. Measurements will be collected at baseline, three months, and six months to ensure comprehensive analysis of the treatment's impact over time.