Efficacy of Recombinant Human Platelet-Derived Growth Factor (rhPDGF) Based Gel in Diabetic Foot Ulcers: A Randomized, Multicent

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Author(s): 
J.V. Hardikar, MS;1 Y. Chiranjeev Reddy, MD;2 Deen Dayal Bung, MS, FRCS;3 Narender Varma, MS;4 Prakash P. Shilotri, MS, FICS;5 E.D. Prasad, MS;2 G. Santa Rao, MS, FICS;6 G. Satyanarayana, MS, MCh;7 K.R. Suresh, DABS, FACS;8 and the HEALACE Study Group

F oot ulcers secondary to peripheral neuropathy and vascular disease are common complications of diabetes and account for high morbidity and mortality. In recent years, with global increases in prevalence of type 2 diabetes, there has been a concomitant increase in diabetic foot ulcers. According to estimates, at least 15% of patients with diabetes develop ulcers of the lower extremity during their lifetimes.1 If improperly or inadequately treated, these ulcers become infected or gangrenous and may ultimately lead to amputation of the affected limb. The annual rate of amputation varies from 41% to 77% per 10,000 patients with diabetes2 and accounts for nearly half of all the lower-limb amputations in hospitalized patients.3 In recent years, there has been a significant increase in the prevalence of diabetes in India, particularly in the urban population.4 In 2000, there were an estimated 31.7 million cases of diabetes reported in India, making it the country with the largest diabetic population. This figure5 is expected to increase to 79.4 million cases by the year 2030. As a result, a parallel increase in the incidence of diabetic foot ulcers is expected.
Until the last decade, aside from controlling plasma glucose and infection with appropriate antidiabetic drugs and antibiotics, diabetic foot ulcers were managed with only good wound care (ie, use of periodic debridement; daily dressing with saline or moist dressings; and use of an appropriate nonweight-bearing regimen). While most of these ulcers can be treated successfully, some remain nonhealing, leading to serious and debilitating complications necessitating amputation of the affected limb. However, the identification of the role of platelet-derived growth factor (PDGF) in the formation of granulation tissue at the wound site and promotion of wound healing have given a new impetus to the development of recombinant human PDGF (rhPDGF). Among the 3 isoforms, the biological activity of rhPDGF homodimer-BB has been shown to be similar to that of naturally occurring PDGF, which includes proliferation of cells involved in the wound repair process. rhPDGF-BB is an approximately 24.5 kDa dimeric protein consisting of 2 identical polypeptide chains that are bound together by disulfide bonds.
Several clinical trials, conducted in Western countries, have demonstrated the safety and efficacy of rhPDGF in the management of diabetic ulcers.6–10 However, results of clinical trials conducted in developed Western countries cannot be directly extrapolated and applied to populations living in developing countries like India due to geographical differences. In fact, a prospective comparative study, conducted in 3 centers in Soest, Germany, Dar-es-Salaam, Tanzania, and Chennai, India on 613 consecutive patients with diabetic foot lesions, documented the regional differences in risk factors and clinical presentation of diabetic foot lesions.11 Such differences further highlight the need to conduct a clinical trial to evaluate the product on Indian patients with diabetic foot ulcers. Keeping these factors in view, clinical safety and efficacy of a topical gel containing 0.01% rhPDGF-BB was tested in Indian patients with lower-extremity diabetic ulcers in a randomized, multicenter, double-blind, placebo-controlled, parallel group study as per the requirements of the Drug Controller General of India.

Methods

Study drug. rhPDGF-BB gel preparation used for the clinical trial was manufactured by insertion of the gene for human PDGF into the bacteria, Escherichia coli. The rhPDGF gel is a low bioburden topical gel formulated with sodium caboxymethylcellulose and other excipients. The authors are not privy to the differences in the formulations available commercially.

References: 

References

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