Diabetes Related Foot Ulcers With Negative Pressure Wound Therapy: A Randomized Controlled Trial

Up to 34% of diabetic patients will develop a Diabetic Foot Ulcer (DFU) during their lifetime. Around one-third of patients with DFU end up with an amputation. The five-year mortality after major lower extremity amputation (LEA), defined as amputation at ankle level or above caused by a DFU, is 52% - 82%. The leading cause of the high mortality is an escalation of already established cardiovascular disease, kidney failure, and poor diabetes regulation. In addition, many amputees suffer from social isolation, depression, and lower quality of life. In 2021, 463 patients with diabetes were amputated in Norway. Approximately 33% of diabetes-related costs have been linked to the treatment of foot ulcers, the majority of which are related to inpatient hospital admissions. Data from England suggest that around 10% of hospital admissions among patients with diabetes were either for ulcer care or amputation. In the United States, $176 billion is spent annually on direct costs for diabetes care. One-third of this expenditure is lower-extremity-related, constituting a substantial cost to society.

A diabetic foot ulcer is challenging to treat and requires tedious care and often repeated surgical debridement, yet only two-thirds heal within 12 months. Both peripheral artery disease (PAD) and neuropathy are risk factors for the development of chronic foot ulceration in people with DM. Long healing times and one-year recurrence rates of over 20% have not improved in the past 20 years despite advances in wound care and revascularization techniques. The high prevalence of infection in DFU and the accompanying economic burden make it essential to develop cost-effective and limb-saving strategies to reduce the burden of DFU infection.

Negative Pressure Wound Therapy (NPWT)) also known as Vacuum Assisted Closure (VAC) therapy, was introduced two decades ago in an attempt to improve wound closure. NPWT aids wound healing by applying sub-atmospheric pressure to reduce inflammatory exudate and promote granulation tissue. It is widely used to manage complex wounds, including open fractures, burns, pressure ulcers, and diabetic foot ulcers. The application of NPWT therapy on chronic DFUs is recommended in several clinical guidelines, including the practical guidelines from the Wound Healing Society and the International Working Group on the Diabetic Foot. However, high-level documentation of the effect of NPWT therapy in the setting of DFU is lacking. Recently, several studies have examined the role of NPWT in the diabetic foot. The overall conclusion is that NPWT may have a positive effect, but the studies have methodological flaws and suffer a high risk of bias. It is, therefore, still being determined whether DFUs heal better with NPWT than with conventional wound care.

The investigators performed an internal quality audit of the treatment of DFU in our department. Despite following recommended procedures, including frequent use of NPWT, the investigators found that patients with DFU had extended hospital stays, underwent serial surgical revisions, and still required major LEA. In an attempt to reduce these complications, the investigators introduced a clinical pathway for patients with DFU to secure prioritized care, fast diagnosis, and treatment. Implementation of the clinical pathway reduced the number of major LEAs, number of surgical procedures, and length of hospital stays. Targeted and fast diagnosis, rapid initiation of treatment, and interdisciplinary collaboration with vascular surgery, infection medicine, and endocrinology were decisive for the outcome. In this new pathway, NPWT treatment was replaced with standard wound care. However, many different variables were altered at the same time. It is, therefore, unclear if the change from NPWT treatment to standard wound care influenced the outcome. Therefore, the purpose of this study is to compare the treatment of DFUs with either NPWT or standard wound care in terms of amputations and mortality, wound closure, hospital stay, and patient-reported outcomes. The study will clarify whether or not NPWT treatment helps treat chronic DFUs. The results will have a significant impact on a large patient group with high morbidity and mortality. The project will help define treatment recommendations that will reduce severe complications of DFU, such as LEA and wound recurrence, and improve the quality of life of diabetic patients. If successful, the project will reduce hospital stays and the number of surgical procedures, thus reducing healthcare costs for the institution and society. The project will obtain new knowledge on a frequently used intervention (NPWT), clarify its indications and limitations, and identify low-value care practices. The results will improve clinical practice and can be implemented in the healthcare system immediately. A prospective randomized controlled trial will be conducted at Akershus University Hospital. Patients referred to Akershus University Hospital will be invited and screened for eligibility. The surgeons will screen patients for trial eligibility by predetermined inclusion- and exclusion criteria and ensure that necessary examinations (MRI, CT, X-ray) have been done per protocol. Patients are invited to participate if all the inclusion criteria and none of the exclusion criteria are met. Eligible patients will receive an assessment by a dedicated healthcare worker, ensuring a thorough evaluation and sufficient reflection period for the patient. An independent third party will obtain informed consent to avoid undue pressure to participate in the study. Informed written and oral consent will be obtained. Patients will be recruited by all physicians who treat DFUs at the institution. A total of 50 patients will be included and randomized (25 patients in each trial arm).

NPWT-group: Patients allocated to NPWT will have the NPWT fitted at the end of wound debridement or partial amputation of the foot in the operating room. Negative pressure wound therapy is a closed, sealed system that applies negative pressure (suction) to the wound surface. Special foam padding is placed on or within the wound. A thin, clear, occlusive dressing seals the wound. A trackpad with suction connects to a canister to collect the fluid drainage. A special pump is used to apply negative pressure. Intermittent suction is maintained by connecting suction tubes from the wound dressing to a vacuum pump and liquid waste collector. The standard negative pressure is 125mmHg. Depending on clinical circumstances, the NPWT dressing is changed every 3-5 days, in theatre, bedside, or at the outpatient clinic, and discontinued as soon as possible. NPWT may be discontinued when the wound secretion is negligible and healthy granulation tissue is present.