Diabetic foot ulcers (DFUs) are among the most severe and costly complications of diabetes mellitus, posing significant challenges to both patients and healthcare providers. Globally, DFUs are a leading cause of non-traumatic lower limb amputations, prolonged hospital stays, and recurrent infections, especially in patients with poor glycemic control and peripheral neuropathy, as described by Kasper et al. (1). The etiology of DFUs is multifactorial, often involving a combination of peripheral arterial disease, neuropathy, foot deformities, and infection. Neuropathy contributes by reducing pain perception, leading to unnoticed trauma and subsequent ulceration (2).

Effective wound healing is highly dependent on the microenvironment of the ulcer. Junker et al. (3) emphasized that a moist wound environment facilitates epithelial migration, promotes angiogenesis, and accelerates healing, compared to dry or excessively wet conditions. Hence, an ideal dressing must maintain moisture, manage exudate, and minimize infection risk.

Povidone-iodine, a commonly used antiseptic dressing, offers broad-spectrum antimicrobial coverage and is traditionally used in DFU management. However, it may not support optimal wound healing due to its potential cytotoxic effects on viable tissue (4). On the other hand, newer technologies such as Negative Pressure Wound Therapy (NPWT) have shown promise. NPWT involves applying sub-atmospheric pressure over a sealed wound, which reduces oedema, increases perfusion, and stimulates granulation tissue formation, thereby enhancing the healing process (5).

Brunicardi et al. (6) noted that NPWT not only promotes early wound contraction and granulation but also reduces bacterial load and the frequency of dressing changes, improving patient comfort. However, comparative studies evaluating NPWT versus traditional dressings like povidone-iodine in resource-limited settings remain sparse.

In this context, our study investigates the effectiveness of NPWT compared to povidone-iodine dressing in healing diabetic foot ulcers. The evaluation employs the Wound Healing Index developed by Medrano et al. (7), which offers a systematic and reproducible measure to assess multiple parameters of wound healing, including tissue quality, edge characteristics, infection signs, and exudate control.

Aims and Objectives

Aim

This study evaluated and compared the efficacy of Negative Pressure Wound Therapy (NPWT) and povidone-iodine dressings in promoting wound healing in patients with diabetic foot ulcers.

Objectives

1. To compare the overall wound healing outcomes of Negative Pressure Wound Therapy (NPWT) versus povidone-iodine dressings using a standardized Wound Healing Index, including parameters such as wound depth, edge characteristics, granulation tissue formation, exudate levels, and infection control.
2. To evaluate the impact on patient-reported outcomes, specifically pain levels during the treatment period.

To provide a preliminary assessment of clinical efficiency and feasibility, including dressing frequency and observed trends in cost-effectiveness during a 10-day observation period.

Study Design and Setting

This was a prospective, randomized, controlled study conducted at CSI Holdsworth Memorial Hospital, a 300-bed tertiary care centre located in Mysore, Karnataka, India. The study was carried out over a two-year period from July 2021 to June 2024.

Study Population

The study enrolled adult inpatients diagnosed with diabetic foot ulcers requiring wound care management in the Department of General Surgery. Eligible participants were randomized into two equal groups of 24 patients each.

Inclusion Criteria

• Age between 35 and 75 years
• Presence of diabetic foot ulcers classified as Wagner Grade 2 or 3
• Informed consent provided for participation and intervention

Exclusion Criteria

• Ulcers associated with osteomyelitis
• Wagner Grade 1 ulcers
• Malignant wounds
• Dry gangrene
• Actively bleeding wounds

Sample Size

Sample size was estimated using the formula:

n = z² × p(1−p) / d²

Using a 95% confidence level (z = 1.96), estimated prevalence (p = 0.012), and margin of error (d = 0.05), the required sample size was calculated to be 19. To ensure robustness, 24 patients were enrolled in each group.

Randomization and Group Allocation

Patients meeting inclusion criteria were randomized into two groups using a computer-generated randomization list.

• Group 1 (Test group) received Negative Pressure Wound Therapy (NPWT)
• Group 2 (Control group) received conventional povidone-iodine dressings

Interventions

Negative Pressure Wound Therapy (NPWT)

Patients underwent thorough surgical debridement followed by NPWT application. A sterile gauze layer soaked in saline was applied to the wound, over which a modified 14F Ryle’s tube was placed and sealed using a surgical glove. Continuous or intermittent suction pressure (−120 to −80 mmHg) was applied using a central or portable suction unit. Dressings were evaluated and changed on postoperative days 2, 4, 6, 8, and 10.

Povidone-Iodine Dressing

After debridement, saline irrigation and topical povidone-iodine dressing were applied. Dressings were changed and evaluated on the same postoperative days as in the NPWT group.

Outcome Measures

Wound healing was assessed using a validated Wound Healing Index (7), which included:

• Wound dimensions and depth (Wagner grading)
• Edge characteristics
• Infection parameters (erythema, oedema, temperature, pale tissue)
• Tissue type (granulation vs. necrotic)
• Exudate classification
• Pain intensity (Visual Analog Scale)

Statistical Analysis

Data were analyzed using SPSS version 20.0. Descriptive statistics were used for demographic data. Categorical variables were analyzed using chi-square tests and contingency coefficients, while continuous variables were compared using independent t-tests. Repeated measures ANOVA was applied for within-subject comparisons over time. A p-value < 0.05 was considered statistically significant

1. Baseline Characteristics

A total of 48 patients with diabetic foot ulcers were enrolled and randomized into two groups: the test group (n = 24), which received Negative Pressure Wound Therapy (NPWT), and the control group (n = 24), which received conventional povidone-iodine dressings. The baseline characteristics were comparable across both groups.

The mean age of participants was similar between groups (58.12 years in NPWT group vs. 58.33 years in control group). Patients aged >55 years constituted a slightly larger proportion in the control group (66.7%) compared to the NPWT group (45.8%), though this difference was not statistically significant (p = 0.146).

There was a male predominance in the study population (75% overall), with no significant difference in sex distribution between groups (p = 0.505).

Regarding comorbid risk factors, such as peripheral vascular disease (PVD), anemia, smoking, alcohol use, malnutrition, and renal failure, the prevalence was evenly distributed between groups. The majority of patients (87.5%) in both groups had at least one identifiable risk factor, and there was no statistically significant difference in the overall distribution of risk factors (p = 0.766).

Table 1. Baseline Demographic and Clinical Characteristics of Study Participants

       Note: No statistically significant differences were observed between the two groups at baseline

2. Wound Characteristics and Clinical Outcomes

2.1 Wound Depth (Wagner Grades)

Wound depth was assessed using the Wagner classification system, limited to Grade 2 and Grade 3 ulcers, as per inclusion criteria. At baseline (Day 0), 54.2% of patients in the NPWT group and 37.5% in the control group had Grade 3 ulcers. Over the 10-day observation period, a progressive reduction in Grade 3 wounds was observed in both groups, indicating healing.

By Day 10:

• In the NPWT group, Grade 3 ulcers decreased from 13 patients (54.2%) to 2 patients (8.3%), while Grade 2 ulcers increased to 22 patients (91.7%). This change was statistically significant (p = 0.002).
• In the control group, Grade 3 ulcers reduced from 9 patients (37.5%) to 0, with all 24 patients presenting as Grade 2 ulcers by Day 10 (p = 0.024)

2.2 Wound Edge Characteristics

Wound edge characteristics were assessed and categorized as diffuse, delimited, damaged, or thickened, following clinical descriptors. Improvement in edge quality indicates advancing epithelialization and reduction in inflammatory margins.

• In the NPWT group, a clear progression from damaged and thickened edges toward diffuse and delimited edges was observed over the 10-day period. On Day 0, 66.7% had thickened or damaged edges; by Day 10, this reduced to 16.7%.
• In the control group, the edge improvement was less pronounced, with 45.8% still showing thickened or damaged edges by Day 10.
• The change in edge quality was statistically significant in the NPWT group (p = 0.000, contingency coefficient = 0.472), but not significant in the control group (p = 0.212, CC = 0.342).

2.3 Infection Control

Wound infection was graded on a 0–4 scale, assessing clinical signs such as erythema, edema, temperature, and pale tissue. Changes in infection severity were monitored across five time points over 10 days.

In the NPWT group, 50% of wounds scored ≥3 on Day 0, indicating moderate to severe infection. By Day 10, only 8.3% of wounds remained in that category, while 62.5% improved to a score of 1 or 0. This change was statistically significant (p = 0.000), with a Cramer’s V of 0.349 indicating a moderate correlation between NPWT and infection reduction

.

In the control group, 41.7% of wounds had infection scores ≥3 at baseline. By Day 10, 20.8% remained at that level. Although statistically significant (p = 0.000), the strength of the association was weaker (Cramer’s V = 0.285).

Both groups experienced infection reduction, but the NPWT group demonstrated faster and more complete resolution, suggesting superior microbial control.

2.4 Granulation Tissue Formation

Granulation tissue is a key marker of wound healing. The presence or absence of visible granulation tissue was documented on alternate dressing days (Days 0, 2, 4, 6, 8, and 10).

In the NPWT group, only 12.5% of patients showed granulation tissue on Day 0, which increased to 95.8% by Day 10. This change was statistically significant (p = 0.000) with a contingency coefficient (CC) of 0.573, indicating a strong association between NPWT and rapid granulation.

In the control group, 25% of patients had granulation tissue on Day 0, increasing to 79.2% by Day 10. This improvement was also statistically significant (p = 0.000), though the strength of association was lower (CC = 0.396).

While both groups exhibited improvement, the NPWT group showed a faster and more pronounced development of granulation tissue, underscoring the role of negative pressure in stimulating wound bed regeneration and angiogenesis.

2.5 Exudate Characteristics

Wound exudate was classified based on volume and containment into four categories: moist, wet, saturated, and leaking. Observations were recorded on alternate dressing days throughout the 10-day treatment period.

In the NPWT group, 50% of wounds were recorded as either saturated or leaking on Day 0. By Day 10, saturated wounds decreased to 12.5%, and leaking wounds to 4.2%. The reduction in high-exudate wounds was statistically significant (p = 0.000), with a contingency coefficient (CC) of 0.506.

In the control group, 50% of wounds were also saturated or leaking at baseline. By Day 10, these reduced to 25% and 8.3%, respectively. This change was also statistically significant (p = 0.000), though with a lower association strength (CC = 0.373).

2.6 Pain Scores

Pain intensity was assessed using the Visual Analog Scale (VAS) ranging from 0 (no pain) to 10 (worst possible pain). Scores were recorded at each dressing time point throughout the 10-day study period.

In the NPWT group, mean pain scores decreased steadily from 6.2 ± 0.84 on Day 0 to 1.83 ± 0.55 by Day 10. The reduction in pain over time was statistically significant (p = 0.000) as determined by repeated measures ANOVA.

In the control group, pain scores declined from 5.6 ± 0.84 on Day 0 to 3.4 ± 0.85 on Day 10. This change was also statistically significant (p = 0.000) using the same test.

A between-group comparison revealed that the NPWT group reported a greater reduction in pain scores over the same duration. On Day 10, the difference in mean pain scores between groups was statistically significant (p = 0.002).

2.7 Summary of Key Findings

Diabetic foot ulcers remain a serious health challenge in India, affecting nearly 15% of diabetic patients at some point during their lifetime [8]. The chronicity and poor healing of these ulcers are exacerbated by peripheral neuropathy, poor glycemic control, infection, and ischemia [9]. Traditional wound care methods such as povidone-iodine dressings have shown limited efficiency in managing advanced ulcers, which necessitates exploration of adjunctive therapies like Negative Pressure Wound Therapy (NPWT).

NPWT operates through mechanisms of macrostrain and microstrain, which promote cellular proliferation, reduce edema, and enhance granulation tissue formation [10]. In our study, patients receiving NPWT showed significantly faster wound healing across all key domains. For instance, wound depth improved significantly in the NPWT group, with the proportion of Grade 3 ulcers declining from 54.2% on Day 0 to 8.3% on Day 10 (p = 0.002), whereas in the control group, the reduction was from 37.5% to 0% (p = 0.024). Although both were statistically significant, the NPWT group demonstrated a more robust transition from deep to superficial ulcers.

Edge characteristics improved markedly in the NPWT group, with 66.7% of wounds having thickened/damaged edges on Day 0, reduced to 16.7% by Day 10 (p = 0.000, contingency coefficient 0.472). In contrast, the control group did not show significant edge improvement (p = 0.212, CC 0.342), reaffirming the superior epithelial remodeling promoted by negative pressure [11].

Infection control is another critical metric in wound management. The NPWT group showed a reduction in high infection scores (≥3) from 50% to 8.3%, whereas the control group saw a less pronounced drop from 41.7% to 20.8%. Both were statistically significant (p = 0.000), but the association strength was greater in the NPWT group (Cramer’s V = 0.349) compared to the control (Cramer’s V = 0.285), underlining NPWT’s superior decontaminating effect [12].

Granulation tissue development, a direct indicator of regenerative activity, reached 95.8% by Day 10 in the NPWT group, compared to 79.2% in the control group (p = 0.000). The association was stronger in the NPWT arm (CC = 0.573) than in the control (CC = 0.396), reflecting the enhanced angiogenesis and fibroblast activity induced by negative pressure therapy [13].

Exudate management is often overlooked but has a significant impact on healing and patient comfort. NPWT was more effective in controlling excess exudate, reducing saturated wounds from 50% to 12.5% and leaking wounds from 20.8% to 4.2% by Day 10 (p = 0.000, CC 0.506). The control group also showed improvement but to a lesser extent (p = 0.000, CC 0.373) [14].

Pain, as quantified by the Visual Analog Scale (VAS), decreased more substantially in the NPWT group (from 6.2 ± 0.84 to 1.83 ± 0.55) than in the control group (from 5.6 ± 0.84 to 3.4 ± 0.85) over the 10-day period. This difference was statistically significant (p = 0.002), likely due to reduced dressing frequency and improved moisture control [15].

The biological rationale behind NPWT’s success lies in its ability to induce microdeformation at the cellular level, promoting mitosis, capillary budding, and growth factor expression [16]. These changes not only speed up healing but also make NPWT a cost-effective modality in the long term, despite higher initial setup costs. Additionally, the occlusive dressing environment helps isolate the wound from external contaminants, further supporting infection control [17].

Anatomically, diabetic foot ulcers often involve poorly vascularized tissue beds. NPWT enhances perfusion and oxygenation in these compromised zones, directly influencing the rate of epithelialization and tissue granulation [18].

Limitations

The 10-day treatment window does not allow for assessment of long-term wound closure, recurrence, or cost-effectiveness over an extended period. Being a single-center study, the results may not be generalizable to all clinical settings, particularly those with limited access to NPWT systems. The sample size of 24 patients per group limits statistical power for detecting rare complications or subtle subgroup differences. Additionally, due to the nature of the intervention, blinding was not feasible, which may introduce observer bias. Lastly, glycemic control was not actively monitored during the study, which may act as a confounding variable in wound healing outcomes.

This study demonstrates that Negative Pressure Wound Therapy (NPWT) is significantly more effective than conventional povidone-iodine dressings in promoting wound healing in patients with diabetic foot ulcers. Over a 10-day observation period, patients treated with NPWT experienced faster reduction in wound depth (p = 0.002), greater improvement in wound edge definition (p = 0.000; CC = 0.472), enhanced infection control (Cramer’s V = 0.349), more rapid granulation tissue formation (CC = 0.573), superior exudate management (CC = 0.506), and significantly lower pain scores by Day 10 (p = 0.002). These findings support NPWT as a clinically superior option for managing diabetic foot ulcers during the acute phase of wound care.

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