The Use of Biochemical Analyzes to Monitor the Development of Wounds

Wound Infection Clinical Trial

— NPWW  

Official title:

The Use of Biochemical Analyzes to Monitor the Development of Wounds: Part 1: Analysis of Wounds Without VAC Therapy: Part 2: Analysis of Wound Fluids Under VAC Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04507724
• Other study ID #: NPWW
• Status: Completed
• Start date: October 19, 2018
• Est. completion date: December 31, 2020

Study information

• Verified date: May 2021
• Source: Qualizyme Diagnostics GmbH & Co KG
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Chronic wounds represent a growing challenge in medical care.

Part 1: The aim of this part of the study was to collect wound swabs and to answer the question whether the rapid diagnostic tool using enzyme activities can display an infection prematurely. This means that an increased enzyme activity (especially MPO, NHE, LYS, gelatinase, pH) measured overed 3 days, would indicate a change in the wound bed (infection, Inflammation) earlier than the regularly performed clinical assessment.

Part 2: The aim of this part of the study was to evaluate (I) the possibility of wound fluid acquisition by means of an "additional collector" during ongoing NPWT and to answer if (II) this secretion can be biochemically analyzed for enzyme activities in order to be able to detect a change in the wound situation at an early stage.

Description:

The study is composed of two parts, which run independently of each other. However, in both parts the course of the wounds is analyzed.

Part 1: Two wound swabs are taken. One used for routinely performed microbiological analysis and the second will be used for biochemical analysis (enzyme activities). The aim of the wound swabs is to answer the question whether the rapid diagnostic tool used in the examination can display an infection prematurely or not. This means that an increased enzyme activity (especially MPO, NHE, LYS, gelatinase, pH) would indicate a change in the wound bed (infection, inflammation) earlier than the regular clinical assessment. These wound swabs are expected to function as an improvement of the biochemical assays or rather of the technology concerning sensitivity and specificity of, for example, the pH number, the MPO, the LYS, the gelatinase and the elastase. In addition to that, the correlation between the Enzyme activities and the course of the infection will be examined. This technology is supposed to be later used as an early infection diagnostic tool in wound fluids. The followup of this testing system is a crucial prerequisite for the application of the technology in VAC therapy (part 2).

Part 2: The findings of this examination will be used to investigate the applicability of the developed in-vitro early infection diagnostic tool in negative-pressure therapy (VAC therapy; vacuum assisted closure).

Patients of the plastic surgery with a NPWT are included in this prospective study. Before the NPWT will be applied, two swabs (biochemical and microbiological analysis) of the wounds will be taken. After installation of the dressing, the connecting tube between the wound and the vacuum-generating device will be cut and an "additional collector" will be inserted. This collector will be changed daily and afterwards the concentrations of enzymes (lysozyme, elastase, myeloperoxidase) will be biochemically analyzed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• signed informed consent

• older than 18 years old

• open wound of varying etiology

• VAC therapy (KCI) (part 2)

Exclusion Criteria:

• under 18 years old

• pregnant women

• less than three measurement data (less than three swabs) = part 1

• VAC-instill therapy = part 2

Related Conditions & MeSH terms

• Biomarker
• Diagnostic Techniques and Procedures
• Negative Pressure Wound Therapy
• Wound
• Wound Contamination
• Wound Infection
• Wounds and Injuries

Locations

Country	Name	City	State
Austria	Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz	Graz

Sponsors (1)

Lead Sponsor	Collaborator
Qualizyme Diagnostics GmbH & Co KG

Country where clinical trial is conducted

Austria, 

References & Publications (23)

Argenta LC, Morykwas MJ. Vacuum-assisted closure: a new method for wound control and treatment: clinical experience. Ann Plast Surg. 1997 Jun;38(6):563-76; discussion 577. — View Citation

Blokhuis-Arkes MH, Haalboom M, van der Palen J, Heinzle A, Sigl E, Guebitz G, Beuk R. Rapid enzyme analysis as a diagnostic tool for wound infection: Comparison between clinical judgment, microbiological analysis, and enzyme analysis. Wound Repair Regen. 2015 May-Jun;23(3):345-52. doi: 10.1111/wrr.12282. Epub 2015 Jun 19. — View Citation

Fleischmann W, Russ M, Westhauser A, Stampehl M. [Vacuum sealing as carrier system for controlled local drug administration in wound infection]. Unfallchirurg. 1998 Aug;101(8):649-54. German. — View Citation

Hasmann A, Gewessler U, Hulla E, Schneider KP, Binder B, Francesko A, Tzanov T, Schintler M, Van der Palen J, Guebitz GM, Wehrschuetz-Sigl E. Sensor materials for the detection of human neutrophil elastase and cathepsin G activity in wound fluid. Exp Dermatol. 2011 Jun;20(6):508-13. doi: 10.1111/j.1600-0625.2011.01256.x. Epub 2011 Apr 13. — View Citation

Hasmann A, Wehrschuetz-Sigl E, Kanzler G, Gewessler U, Hulla E, Schneider KP, Binder B, Schintler M, Guebitz GM. Novel peptidoglycan-based diagnostic devices for detection of wound infection. Diagn Microbiol Infect Dis. 2011 Sep;71(1):12-23. doi: 10.1016/j.diagmicrobio.2010.09.009. Epub 2011 Mar 9. — View Citation

Hasmann A, Wehrschuetz-Sigl E, Marold A, Wiesbauer H, Schoeftner R, Gewessler U, Kandelbauer A, Schiffer D, Schneider KP, Binder B, Schintler M, Guebitz GM. Analysis of myeloperoxidase activity in wound fluids as a marker of infection. Ann Clin Biochem. 2013 May;50(Pt 3):245-54. doi: 10.1258/acb.2011.010249. — View Citation

Heinzle A, Papen-Botterhuis NE, Schiffer D, Schneider KP, Binder B, Schintler M, Haaksman IK, Lenting HB, Gübitz GM, Sigl E. Novel protease-based diagnostic devices for detection of wound infection. Wound Repair Regen. 2013 May-Jun;21(3):482-9. doi: 10.1111/wrr.12040. Epub 2013 Apr 29. — View Citation

Huang C, Leavitt T, Bayer LR, Orgill DP. Effect of negative pressure wound therapy on wound healing. Curr Probl Surg. 2014 Jul;51(7):301-31. doi: 10.1067/j.cpsurg.2014.04.001. Epub 2014 Apr 26. Review. — View Citation

Isago T, Nozaki M, Kikuchi Y, Honda T, Nakazawa H. Effects of different negative pressures on reduction of wounds in negative pressure dressings. J Dermatol. 2003 Aug;30(8):596-601. — View Citation

Izadi K, Ganchi P. Chronic wounds. Clin Plast Surg. 2005 Apr;32(2):209-22. Review. — View Citation

James GA, Swogger E, Wolcott R, Pulcini Ed, Secor P, Sestrich J, Costerton JW, Stewart PS. Biofilms in chronic wounds. Wound Repair Regen. 2008 Jan-Feb;16(1):37-44. Epub 2007 Dec 13. — View Citation

Klebanoff SJ. Myeloperoxidase. Proc Assoc Am Physicians. 1999 Sep-Oct;111(5):383-9. Review. — View Citation

Ladwig GP, Robson MC, Liu R, Kuhn MA, Muir DF, Schultz GS. Ratios of activated matrix metalloproteinase-9 to tissue inhibitor of matrix metalloproteinase-1 in wound fluids are inversely correlated with healing of pressure ulcers. Wound Repair Regen. 2002 Jan-Feb;10(1):26-37. — View Citation

McDaniel JC, Roy S, Wilgus TA. Neutrophil activity in chronic venous leg ulcers--a target for therapy? Wound Repair Regen. 2013 May-Jun;21(3):339-51. doi: 10.1111/wrr.12036. Epub 2013 Mar 28. Review. — View Citation

Morykwas MJ, Argenta LC, Shelton-Brown EI, McGuirt W. Vacuum-assisted closure: a new method for wound control and treatment: animal studies and basic foundation. Ann Plast Surg. 1997 Jun;38(6):553-62. — View Citation

Nuutila K, Yang L, Broomhead M, Proppe K, Eriksson E. Novel negative pressure wound therapy device without foam or gauze is effective at -50 mmHg. Wound Repair Regen. 2019 Mar;27(2):162-169. doi: 10.1111/wrr.3. Epub 2018 Oct 31. — View Citation

Schiffer D, Blokhuis-Arkes M, van der Palen J, Sigl E, Heinzle A, Guebitz GM. Assessment of infection in chronic wounds based on the activities of elastase, lysozyme and myeloperoxidase. Br J Dermatol. 2015 Dec;173(6):1529-31. doi: 10.1111/bjd.13896. Epub 2015 Oct 29. — View Citation

Schiffer D, Tegl G, Heinzle A, Sigl E, Metcalf D, Bowler P, Burnet M, Guebitz GM. Enzyme-responsive polymers for microbial infection detection. Expert Rev Mol Diagn. 2015;15(9):1125-31. doi: 10.1586/14737159.2015.1061935. Epub 2015 Jul 16. Review. — View Citation

Steenvoorde P, van Engeland A, Oskam J. Vacuum-assisted closure therapy and oral anticoagulation therapy. Plast Reconstr Surg. 2004 Jun;113(7):2220-1. — View Citation

Tegl G, Schiffer D, Sigl E, Heinzle A, Guebitz GM. Biomarkers for infection: enzymes, microbes, and metabolites. Appl Microbiol Biotechnol. 2015 Jun;99(11):4595-614. doi: 10.1007/s00253-015-6637-7. Epub 2015 May 9. Review. — View Citation

Timmers MS, Graafland N, Bernards AT, Nelissen RG, van Dissel JT, Jukema GN. Negative pressure wound treatment with polyvinyl alcohol foam and polyhexanide antiseptic solution instillation in posttraumatic osteomyelitis. Wound Repair Regen. 2009 Mar-Apr;17(2):278-86. doi: 10.1111/j.1524-475X.2009.00458.x. — View Citation

Trengove NJ, Bielefeldt-Ohmann H, Stacey MC. Mitogenic activity and cytokine levels in non-healing and healing chronic leg ulcers. Wound Repair Regen. 2000 Jan-Feb;8(1):13-25. — View Citation

Yager DR, Zhang LY, Liang HX, Diegelmann RF, Cohen IK. Wound fluids from human pressure ulcers contain elevated matrix metalloproteinase levels and activity compared to surgical wound fluids. J Invest Dermatol. 1996 Nov;107(5):743-8. — View Citation

* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: biochemical analysis of wounds	Elevated enzyme activities (biochemical analysis of wound swabs) give information of the condition of the wound bed (infection, inflammation).	during hospitalization
Primary	Part 2: Descriptive assessment of the feasibility of collecting wound fluid during ongoing negative pressure wound therapy	The aim is to answer the question if it is feasible to collect wound fluid during ongoing negative pressure wound therapy and analyze this wound fluid biochemically.	during negative pressure wound therapy
Secondary	Part 2: Evaluating changes in enzyme activities in the collected wound fluid	The collected wound fluid will be analyzed biochemically daily over three days. This might give as informations of wounds as an "in-vitro early infection diagnostic tool"	Starting immediately after installation of the negative-pressure dressing and lasting for 3 days.