|Year : 2018 | Volume
| Issue : 1 | Page : 28-31
A randomized controlled trial to compare efficacy of collagen granule-based dressing versus conventional dressing in the management of diabetic foot ulcers
SS Shimikore, Gaurav B Pawar
Department of Surgery, J. N. Medical College, KLE University, Belagavi, Karnataka, India
|Date of Web Publication||11-Jun-2018|
Dr. S S Shimikore
Department of Surgery, J. N. Medical College, KLE University, Belagavi - 590 010, Karnataka
Source of Support: None, Conflict of Interest: None
Background and Objective: Diabetic foot ulcers are the most common reason for frequent hospitalization of diabetic patients. Management of ulcers by appropriate clinical practices such as thorough dressing and sterile wound creation to achieve improved mobility as well as completeness of healing are the significant goals of the clinicians. The current study aimed to compare the efficacy of collagen granule-based dressing over the conventional dressing in the management of diabetic foot ulcers. Materials and Methods: A randomized controlled trial was conducted from January 2013 to December 2013. A total of 60 patients having diabetic foot ulcers were studied. Routine investigations such as complete blood count, fasting blood sugar, culture and antibiotic sensitivity, and X-ray of the foot were performed. Patients were divided into two groups: group A (n = 30; treated with topical collagen granules dressing) and Group B (n = 30; treated with conventional dressing). Data were analyzed using Microsoft Excel Spreadsheet, categorical data were expressed as rates, ratios, and percentages, and the comparison was performed using Chi-square test and Fisher's exact test. Results: At the end of week 2, the mean wound area, after the dressing, was significantly less in Group A compared to Group B (P ≤ 0.001). The study also showed lower number of patients with slough/necrotic tissue in Group A than in Group B (P ≤ 0.001). At the end of week 4, no patient with wound discharge was observed in Group A compared to Group B (P = 0.005). Conclusion: The treatment of diabetic foot ulcers with collagen granule resulted in the reduction in wound area, slough/necrotic tissue, and wound discharge, leading to early wound healing compared to conventional dressing.
Keywords: Collagen granule dressing, diabetes mellitus, diabetic foot ulcers
|How to cite this article:|
Shimikore S S, Pawar GB. A randomized controlled trial to compare efficacy of collagen granule-based dressing versus conventional dressing in the management of diabetic foot ulcers. Arch Med Health Sci 2018;6:28-31
|How to cite this URL:|
Shimikore S S, Pawar GB. A randomized controlled trial to compare efficacy of collagen granule-based dressing versus conventional dressing in the management of diabetic foot ulcers. Arch Med Health Sci [serial online] 2018 [cited 2019 Feb 22];6:28-31. Available from: http://www.amhsjournal.org/text.asp?2018/6/1/28/234099
| Introduction|| |
Diabetic foot ulcer is an expansive and disabling clinical problem, which can lead to prolonged course treatment and amputation of the limb. Foot complications in diabetic patients are the most important public health challenges, globally. Approximately 25% of diabetic patients develop foot ulcers each year, and the most frequent case of hospitalization of diabetic patients is the existence of serious foot or lower extremity problems., More than 15% of foot ulcer cases result in amputation of the limb or foot.
The management of diabetic foot ulcers includes relieving the wound using suitable therapeutic footwear. Other recommendations include the use of daily saline or similar dressings that allow a moist wound environment, debridement, antibiotic therapy if osteomyelitis or cellulite is present, optimal control of blood glucose level, and assessment and correction of peripheral arterial insufficiency. Various topical medications and gels have been promoted for ulcer healing and maintenance. In addition to holding the infection, an ideal wound care product should also protect the normal tissues and should not interfere with the normal wound healing. At present, diabetic foot ulcers are being managed by local dressing with agents such as povidone-iodine, eusol, and hydrogen peroxide, but they have their own restrictions. Application of collagen granules may be an efficient alternative to the currently used conventional methods of dressings for diabetic wounds.
Proteins are the natural polymers, which make up approximately 15% of the human body. Amino acids are the building blocks of all proteins. Collagen is the major protein of the extracellular matrix and is the most abundant protein found in mammals comprising 70%–80% of the skin (dry weight) and 25% of the entire protein. Collagen acts as a structural gallow in the tissues. The key characteristic of all collagen molecules is their strong, triple-stranded helical structure. Types I, II, and III are the three main types of collagen found in the connective tissue and constitute 90% of all the collagen in the human body. It is obvious that collagen and collagen-derived fragments control many cellular functions including cell shape and differentiation, migration, and synthesis of a number of proteins. Hence, collagen plays a central role at each stage of wound healing.
Reckoning at the advantages of collagen granule-based dressing for more skillful control of wound healing, the present work was designed to compare the efficacy of collagen granule-based dressing versus the formal dressing in the healing of diabetic foot ulcers.
| Materials and Methods|| |
In this randomized controlled study, a total of 60 patients who had diabetic foot ulcers measuring >1 cm with slough, foul smell, and minimal granulation tissue were included. The study was conducted at the Department of General Surgery from January 2013 to December 2013. Diabetic patients having fasting blood glucose level <127 mg/dl, aged >20 years, suffering from foot ulcers with >1 cm slough, foul smell, and minimal granulation tissue were included. Patients who had ulcers of Grades 3, 4, and 5 of Wagner's classification, no peripheral pulses, immunocompromised, malnourished status, and patients with associated malignancies and metabolic disorders were excluded from this study.
The selected patients were divided into two groups of 30 each based on the computer-generated random numbers. This study was approved by the Institutional Ethical and Research Committee. The eligible patients who fulfilled the selection criteria were informed in detail about the study, and written informed consent was obtained.
The demographic data and ulcer characteristics were collected through an interview. Patients were enquired about the history of ulcer duration, diabetes, and treatment. Further, these patients were subjected to clinical examination. The findings were noted on a predesigned and pretested pro forma. For investigations, the patients were examined for complete blood count, fasting blood glucose level, culture and antibiotic sensitivity, blood urea and serum creatinine levels, and protein levels, and X-ray of the foot was performed for anteroposterior and lateral view.
Assessment of wound
Ulcer size was assessed at the end of every 2nd and 4th week. Ulcer mapping was done, and the size was recorded by superimposing a gauze on the ulcer and thus assessing the largest dimension of the ulcer. The size was measured twice and the mean of the two measurements was considered as the size of the wound. The wound was also observed for granulation, tissue quality, and discharge at the end of 2nd and 4th week.
The data obtained were coded and entered into Microsoft Excel Spreadsheet. The categorical data were expressed as rates, ratios, and percentages, and the comparison was made using Chi-square test and Fisher's exact test. Continuous data were represented as mean ± standard deviation, and the independent sample t-test was used for comparison. P ≤ 0.05 at 95% confidence interval was considered statistically significant.
| Results|| |
On gender analysis, it was found that Group A had 22 men and 8 women and Group B comprised 18 men and 12 women. The mean age of patients in Group A was 49.00 ± 8.15 years, whereas in Group B, it was 49.60 ± 10.39 years. Significant difference was not observed in the duration of diabetes between Groups A and B (5.58 ± 2.91 years vs. 5.77 ± 2.40 years, P = 0.8). Similarly, no significant difference was observed in fasting blood glucose levels between Groups A and B (178.47 ± 47.00 mg/dl vs. 172.27 ± 33.27 mg/dl; P = 0.558).
The mean wound area before dressing was comparable in Group A (32.30 ± 13.75 mm 2) and Group B (39.63 ± 14.69 mm 2; P = 0.051). It was observed that a number of patients with wound discharge (P = 0.5) and slough/necrotic tissue (P = 0.052) were comparable between Groups A and B [Table 1].
At the end of 2nd week, the mean wound area, after the dressing, was significantly less in Group A (15.77 ± 8.44 mm 2) when compared to Group B (30.50 ± 13.6 mm 2; P ≤ 0.001). No significant difference was observed in the number of patients with wound discharge in Groups A and B (P = 0.112). A significantly lower number of patients with slough/necrotic tissue was observed in Group A (n = 2) compared to Group B [n = 17, P ≤ 0.001; [Table 2].
After the patients crossed 4 weeks of dressing, healthy wounds were observed and conventional methods such as skin grafting were used, wherever necessary; and some wounds, which reduced in size, were subjected for secondary healing with proper care. Some wounds, which did not improve with conventional dressing, were shifted to collagen granule dressing to convert those to healing ulcers and then treated subjectively further. At the end of week 4, none of the patients in Group A were seen with discharge when compared to Group B (P = 0.005). Furthermore, no significant difference was observed in patients with slough/necrotic tissue in both groups [P = 0.119; [Table 3].
| Discussion|| |
Collagen is an endogenous substance, which is a crucial structural element in the connective tissue, especially of the skin. The significance of collagen has been shown for a long time for the basic reason that the consequence of tissue repair in wounds always results in a scar, which is made out of collagenous fibers. Contemporary research indicates that collagen dressing elevates the fibroblast development, which has hydrophilic property that promotes fibroblast permeation. This in turn enhances the deposition of collagen fibers, raises the uptake of fibronectin, and preserves macrophages, leukocytes, and epithelial cells, which assist in maintaining the microenvironment of the wound. It is evident that collagen and collagen-determined pieces control numerous cell capacities, including cell shape and separation, movement, and blend of various proteins. Hence, collagen plays a key role in every stage of injury management. In this study, age, sex, history of diabetics, and ulcer characteristic of the subject population  were studied, which were comparable, ruling out bias in the final results.
Limited data are available on the effect of topical collagen granule-based dressing in diabetic foot ulcers. Veves et al. conducted a randomized controlled trial (RCT) in which the collagen dressing was compared with standard treatment in diabetic foot ulcers. The results showed that collagen granules have wound-healing property. In another study by Lázaro-Martínez et al., it was demonstrated that protease-modifying dressings in patients with neuropathic diabetic foot ulcers initiate better tissue regeneration.
Initially, patients in both the groups were administered a broad-spectrum antibiotic and then were switched over to necessary antibiotics as per the bacterial culture and antibiotic sensitivity reports. In a study by Lobmann et al., it was reported that local treatment with a protease inhibitor dressing/collagen dressing has a beneficial effect on wound healing. Oxidized regenerated collagen matrix effectively reduces the levels of protease in the wound exudate and size in patients with diabetic foot ulcer. Wollina et al. reported some effects of topical collagen-based matrix on the microcirculation and wound healing in patients with chronic leg ulcers. The preliminary observations showed that topical collagen improves microcirculation, which is a key parameter of granulation tissue formation. The determinations of the present work were consistent with these findings.
Collagen granule-based dressing has more benefits over conventional dressing in terms of collagen formation with greater simplification in inflammatory cells during healing days, resulting in decreased days of healing. However, conventional dressing has a minimal collagen formation and high grade of lighting during the healing days with the maximum exudate formation, resulting in increased days of healing., A collagen granule-based dressing has another preferred standpoint over routine dressing, that is, it is nonimmunogenic, nonpyrogenic, ease of application, hypoallergenic, and torment free. Another study also reported a significant improvement in diabetic foot ulcer patients with early and better mobilization, reduced infection development, and improved comfortability compared to conventional therapy. A study by Veves and Sheehan assessed healing of wounds in 270 patients, and after 6 months of follow-up, the collagen dressings showed improved healing.
Overall, the present study demonstrated that diabetic foot ulcers treated with collagen granule-based dressing are efficacious in terms of reduction in wound area, slough/necrotic tissue, and discharge and increase in granulation tissue, resulting in early wound healing.
RCT is considered as a “gold standard” for treatment efficacy study, so it minimizes limitations in study design aspects. However, few subjective limitations can be outlined, which include as follows: the study is limited to diabetic foot ulcer in patients with no other comorbidities; the study duration was 1 year only, but considerate number of patients were included to perform the RCT; although the amount of collagen granules poured on the wound might be different, it is important to cover the wound surface in a single layer, and this factor was taken care of, and the study was done in a single setting.
Further research with a larger sample size and longer duration is required to extrapolate the findings of the current study.
| Conclusion|| |
Grounded along the outcomes of this work, it may be concluded that diabetic foot ulcers treated with collagen granule are efficacious in terms of reduction in wound area, slough/necrotic tissue, and discharge, resulting in early wound healing compared to conventional dressing.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Most RS, Sinnock P. The epidemiology of lower extremity amputations in diabetic individuals. Diabetes Care 1983;6:87-91.
Smith DM, Weinberger M, Katz BP. Predicting nonelective hospitalization: A model based on risk factors associated with diabetes mellitus. J Gen Intern Med 1987;2:168-73.
Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA 2005;293:217-28.
Ramsey SD, Newton K, Blough D, McCulloch DK, Sandhu N, Reiber GE, et al.
Incidence, outcomes, and cost of foot ulcers in patients with diabetes. Diabetes Care 1999;22:382-7.
Hilton JR, Williams DT, Beuker B, Miller DR, Harding KG. Wound dressings in diabetic foot disease. Clin Infect Dis 2004;39 Suppl 2:S100-3.
Edmonds M, Foster A. The use of antibiotics in the diabetic foot. Am J Surg 2004;187:25S-8S.
Jeffery J. Metalloproteinases and tissue turnover. Wounds 1995;7:13A-22A.
Madri JA, Marx M. Matrix composition, organization and soluble factors: Modulators of microvascular cell differentiation in vitro
. Kidney Int 1992;41:560-5.
Lazovic G, Colic M, Grubor M, Jovanovic M. The application of collagen sheet in open wound healing*. Ann Burns Fire Disasters 2005;18:151-6.
Singh O, Gupta SS, Soni M, Moses S, Shukla S, Mathur RK, et al.
Collagen dressing versus conventional dressings in burn and chronic wounds: A retrospective study. J Cutan Aesthet Surg 2011;4:12-6.
] [Full text]
Park SN, Lee HJ, Lee KH, Suh H. Biological characterization of EDC-crosslinked collagen-hyaluronic acid matrix in dermal tissue restoration. Biomaterials 2003;24:1631-41.
Brett D. A review of collagen and collagen-based wound dressings. Wounds 2008;20:347-56.
Shahi SK, Kumar A, Kumar S, Singh SK. Prevalence of diabetic foot ulcer and associated risk factors in diabetic patients from North India. J Diabet Foot Compli 2012;4:83-91.
Veves A, Sheehan P, Pham HT. A randomized, controlled trial of Promogran (a collagen/oxidized regenerated cellulose dressing) vs. standard treatment in the management of diabetic foot ulcers. Arch Surg 2002;137:822-7.
Lázaro-Martínez JL, García-Morales E, Beneit-Montesinos JV, Martínez-de-Jesús FR, Aragón-Sánchez FJ. Randomized comparative trial of a collagen/oxidized regenerated cellulose dressing in the treatment of neuropathic diabetic foot ulcers. Cir Esp 2007;82:27-31.
Lobmann R, Zemlin C, Motzkau M, Reschke K, Lehnert H. Expression of matrix metalloproteinases and growth factors in diabetic foot wounds treated with a protease absorbent dressing. J Diabetes Complications 2006;20:329-35.
Ulrich D, Smeets R, Unglaub F, Wöltje M, Pallua N. Effect of oxidized regenerated cellulose/collagen matrix on proteases in wound exudate of patients with diabetic foot ulcers. J Wound Ostomy Continence Nurs 2011;38:522-8.
Wollina U, Schmidt WD, Krönert C, Nelskamp C, Scheibe A, Fassler D, et al.
Some effects of a topical collagen-based matrix on the microcirculation and wound healing in patients with chronic venous leg ulcers: Preliminary observations. Int J Low Extrem Wounds 2005;4:214-24.
Rao H, Pai A, Hussein I, Arun A, Ram HS, Pai A, et al.
Acomparative study between collagen dressings and conventional dressings in wound healing. Int J Collab Res Int Med Public Health 2012;4:611-23.
Kshirsagar AY, Vekariya MA, Gupta V, Pednekar AS, Mahna A, Patankar R, et al.
Acomparative study of colostrum dressing versus conventional dressing in deep wounds. J Clin Diagn Res 2015;9:PC01-4.
[Table 1], [Table 2], [Table 3]