Efficacy of Negative Pressure Wound Therapy Versus Conventional Moist Dressings on Diabetic Foot Ulcer Healing Trajectories: A Randomized Controlled Trial Evaluating Clinical and Biophysical Outcomes

Introduction Diabetic foot ulcers (DFUs) represent one of the most debilitating, complex, and costly microvascular and macrovascular complications of diabetes mellitus (DM), imposing profound clinical, economic, and psychosocial burdens on patients and healthcare systems globally. Globally, an estimated 15% to 25% of individuals with diabetes will develop a DFU during their lifetime, with up to 20% of these cases progressing to lower-extremity amputations accounting for over 80% of non-traumatic amputations worldwide (Theodorakopoulos & Armstrong, 2025; Villalba-Aguilar et al., 2025). Pathophysiologically, DFUs result from a synergistic triad of peripheral neuropathy, peripheral arterial disease, and chronic hyperglycemia-induced microvascular dysfunction, compounded by impaired immune surveillance and dysregulated inflammatory signaling (Yang et al., 2021; Zeng et al., 2025). In Jordan, the prevalence of DM among adults has reached approximately 23.7%, reflecting a steep upward trajectory over time. Epidemiologic studies and comprehensive reviews indicate that between 4.6% and 5.3% of diabetic patients in Jordan suffer from active foot ulcers, while an additional 17.2% are categorized as having feet at high risk for ulceration (AlAyed et al., 2017; Mairghani et al., 2017). This growing burden is compounded by systemic healthcare challenges, including restricted primary care access, a scarcity of specialized wound care facilities outside major urban hubs such as Amman and Irbid, and socioeconomic barriers to proper offloading adherence and glycemic self-management factors that collectively lead to delayed presentation, elevated infection rates, and prolonged healing trajectories (Abirami et al., 2024; Dharaneesh et al., 2025). Within this clinical setting, local wound bed management remains a critical therapeutic frontier. Conventional moist wound dressings have long served as the baseline standard of care due to their wide availability, low direct cost, and ease of application (Nirupam & Vinayak, 2022; Ravisankar et al., 2022). However, conservative modalities often fail to resolve the core pathophysiological derangements of chronic DFUs such as persistent bacterial biofilm colonization, excessive proteolytic matrix metalloproteinase activity, interstitial edema leading to localized tissue hypoxia, and stagnant granulation bed development (Xin et al., 2024; Zeng et al., 2025). Clinically, these shortcomings manifest as prolonged healing times, frequent dressing changes (typically required every 24-48 hours), elevated infection risks, and recurrent hospital readmissions (Sharaf et al., 2025; Sheen et al., 2021). In contrast, Negative Pressure Wound Therapy (NPWT), delivered via Vacuum-Assisted Closure (VAC) systems, represents an active, biophysical modality grounded in mechanical tissue stimulation rather than passive coverage (Rodríguez Angulo et al., 2025). NPWT exerts its therapeutic effects through four interdependent physiological mechanisms: Macrodeformation: Direct mechanical contraction that approximates wound margins; Microdeformation: Cellular-level mechanotransduction that stimulates fibroblast proliferation, endothelial cell migration, and collagen matrix deposition; Exudate Evacuation: Continuous clearance of excess fluid, inflammatory cytokines, proteases, and bacterial loads; and Perfusion Modulation: Reduction of interstitial edema and restoration of microvascular blood flow (Saramago et al., 2025; Xin et al., 2024; Zeng et al., 2025). Recent syntheses of global data including meta-analyses covering over 1,900 patients across 23 studies confirm that NPWT significantly reduces time to complete wound closure and increases the probability of full epithelialization at 12 weeks compared to conventional dressings (Villalba-Aguilar et al., 2025; Yang et al., 2024). Despite robust international evidence supporting NPWT in high-income settings, the translational validity, feasibility, and practical implementation of NPWT within Middle Eastern and resource-constrained developing healthcare environments like Jordan remain insufficiently explored. Specifically, there is a lack of rigorous experimental studies evaluating NPWT within national healthcare infrastructures governed by the Ministry of Health and the Royal Medical Services, particularly regarding patient adherence, device feasibility, and interaction with patient-specific covariates (e.g., age, gender, employment, and baseline glycemic control, HbA1c). To address these knowledge gaps, a Randomized Controlled Trial (RCT) was conducted to evaluate the comparative clinical efficacy and synergistic potential of Negative Pressure Wound Therapy (NPWT) versus conventional moist dressings on wound healing outcomes among diabetic foot ulcer patients in Jordan. By assessing the biophysical impacts of NPWT across 13 distinct anatomical and physiological subdomains measured using the Bates-Jensen Wound Assessment Tool (BWAT©) alongside Jordan-specific clinical and social determinants, this research provides contextualized empirical evidence to support the National Diabetes Strategy and advance sustainable DFU management. Alternative Hypothesis (H1): Patients with diabetic foot ulcers receiving Negative Pressure Wound Therapy (NPWT) in a randomized controlled trial will exhibit statistically significant improvements in wound healing parameters evidenced by accelerated healthy granulation tissue formation, enhanced epithelial cell migration/proliferation, greater percentage reductions in wound surface area, diminished exudate/necrotic burden, and lower post-intervention BWAT scores compared to control patients receiving conventional wound dressings. Null Hypothesis (H0): There will be no statistically significant difference in wound healing outcomes or BWAT scores (including granulation tissue formation, epithelialization, percentage reduction in wound surface area, and overall healing rate) between diabetic foot ulcer patients treated with NPWT and those receiving conventional dressings. Previous literature indicates that NPWT (also known as vacuum-assisted closure (VAC)) significantly enhances tissue development and local blood flow, accelerates granulation, decreases wound size, and reduces length of hospital stay while maintaining comparable infection rates (Villalba-Aguilar et al., 2025; Yang et al., 2024).

Materials and Methods

1. Research Design This study was designed as a randomized controlled trial (RCT) with a parallel-group, pretest-posttest comparative design. The objective of this study was to evaluate the safety and efficacy of vacuum sealing drainage (VSD) / negative pressure wound therapy (NPWT) versus conventional wound dressing techniques in patients presenting with chronic diabetic foot ulcers (DFUs). Previous literature indicates that NPWT (also known as vacuum-assisted closure (VAC)) significantly enhances tissue development and local blood flow, accelerates granulation, decreases wound size, and reduces length of hospital stay while maintaining comparable infection rates.
2. Setting This study was conducted at the National Center for Diabetes, Endocrinology, and Genetics (NCDEG), a tertiary referral center located in Amman, Jordan. Jordan is a lower-middle-income country covering an area of approximately 89,300 km2, with arable land accounting for only 7.8% of its total surface. The total population is approximately 9.8 million, with 90.3% residing in urban regions. Additionally, Jordan hosts a substantial refugee population, including approximately 629,245 registered Syrian refugees. Over the past two decades, Jordan's healthcare system has advanced significantly, becoming one of the leading healthcare models in the Middle East. The system operates within a comprehensive framework comprising three primary sectors: public, private, and non-profit organizations. Overall, health insurance coverage extends to more than 70% of the Jordanian population. As a national specialized tertiary referral center, the NCDEG manages complex diabetes mellitus (DM) cases across the country, primarily serving a catchment population of 4.1 million residents in Amman. In 2017 alone, the center delivered outpatient clinical services to 116,226 patients, including both insured and non-insured individuals. Standard care at the NCDEG involves routine follow-up visits every three months, during which vital and anthropometric parameters such as height, weight, and blood pressure are measured, alongside regular fundoscopic exams, diabetic foot evaluations, and glycated hemoglobin (HbA1c) assessments. Furthermore, annual screenings for lipid profiles and microvascular complications are conducted as standard clinical practice for all DM patients at the center. For the current study, data collection was carried out from January 2026 May 2026. The clinical setting provided standardized wound assessment, surgical debridement, and follow-up care for all enrolled participants.
3. Participants and Eligibility Criteria 3.1 Inclusion Criteria Aged 18 years or older. Diagnosed with superficial chronic diabetic foot ulcers (partial- or full-thickness) located on the plantar surface, metatarsal heads, or sole (Grade 1/clean ulcers). Had a wound length ranging from 10 to 15 cm. Had controlled diabetes mellitus with stable comorbid conditions (e.g., hypertension or non-end-stage renal disease). Were able to speak and read Arabic. Were able to perform activities of daily living (ADLs) independently. Provided voluntary written informed consent to participate in the study.

3.2 Exclusion Criteria Underlying osteomyelitis, Charcot's joint/arthropathy, or DFUs classified as Wagner Grade 3, 4, or 5. Severe peripheral vascular/arterial diseases, venous insufficiency, or bilateral involvement of both feet. Coagulopathic conditions, active bleeding tendencies, or severe immunocompromising diseases. Cognitive or mental impairments preventing informed participation. Severe diabetic complications (e.g., acute cerebrovascular disease). Pregnancy, active fever, or acutely infected wounds at baseline. 4. Sample Size and Sampling Technique 4.1 Sample Size Determination The sample size was determined based on statistical power calculations targeting an 80% power level and a significance threshold of p < 0.05, derived from expected differences in wound reduction rates reported in prior literature. Accounting for an anticipated dropout rate of approximately 10%, a total of 60 eligible patients were enrolled and randomly allocated into two equal groups (n = 30 per group: Intervention Group [VAC] and Control Group [Conventional Dressing]). All 60 participants completed the 3-month trial and were included in the final comparative statistical analysis (N = 60).

4.2 Sampling Technique A simple random sampling technique (lottery method) was utilized to select participants and minimize selection bias. Diabetic patients attending the outpatient clinics from Sunday to Thursday were screened daily for eligibility. Medical registration numbers of eligible patients were drawn randomly without replacement until the target intake (approximately six patients per day) was reached. 5. Randomization, Allocation, and Blinding 5.1 Randomization and Allocation Concealment Following baseline screening, participants were randomly assigned to either Group A (Intervention/VAC) or Group B (Control/Standard Dressing) using a computer-generated randomization sequence. Allocation concealment was strictly maintained using sequentially numbered, sealed, opaque envelopes prepared by an independent researcher who was not involved in participant recruitment or treatment procedures.