Clinical trial NCT01480362: Treatment Study of Negative Pressure Wound Therapy for Diabetic Foot Wounds
Official title: Randomized, Controlled Clinical Trial Evaluating the Efficacy and Clinical Effectiveness of Negative Pressure Wound Therapy for the Treatment of Diabetic Foot Wounds When Compared to Standard Wound Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Foot Ulcer, Diabetic
Keywords: Diabetic foot wound
Amputation wound
Chronic wound
Lead sponsor: University of Witten/Herdecke
Sponsor class: OTHER
Collaborators: name: Kinetic Concepts, Inc.
name: Smith & Nephew Wound Management Inc
First posted: 2011-11-28
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: On behalf of a consortium of 19 health insurance companies the Institute for Research in Operative Medicine as part of the University of Witten / Herdecke gGmbH is planning and conducting a clinical study evaluating the efficacy and effectiveness of negative pressure wound therapy in the treatment of wound healing disorders of the foot, which are caused by diabetes mellitus.

This german multicenter study is due to evaluate whether the negative pressure wound therapy or the control therapy (standard wound therapy following the guidelines) is superior.

Patients will be randomly assigned to the two study arms. Both patients and the treatment staff know about the specific allocation to the negative pressure wound therapy or standard wound therapy arm.

A photo documentation and a computer-based evaluation of the wound images will be performed. This is done centrally by independent examiners, who don't know neither the patient nor the treatment assignment.

It is believed that the application of the negative pressure wound therapy systems compared to standard therapy of diabetic foot wounds will lead more frequent and more rapid to the achievement of complete wound closure and that the use of negative pressure wound therapy is an effective and safe therapy option for the treatment of diabetic foot wounds in inpatient and outpatient care.

Patient´s to be included into the study should have either a chronic diabetic foot wound existing longer than 4 weeks whereas dead tissue components must be completely removed by the doctor or a wound after amputation of foot parts.

The study treatment may have already started in the hospital if applicable. The further wound treatment will be mainly performed within outpatient care. Study Participants will return to the study centre for regular study visits or even for wound treatment.

The comparison of the outcomes of both study arms will give valuable information about the efficacy of negative pressure wound therapy in inpatient as well as outpatient care. These results should be provided until the end of 2016 as a basis for the decision of the Federal Joint Committee to answer the question if the negative pressure wound therapy can be approved as a standard service for reimbursement by health insurance companies.

Detailed description: This study project as part of a European tender has the aim to prove efficacy and effectiveness of negative pressure wound therapy in the management of patients with chronic diabetic foot wounds. The tasks within the study project have been assigned to three contractors / institutions.

On behalf of a consortium of 19 health insurance companies with a central contact consisting of the "AOK-Bundesverband GbR", "Verband der Ersatzkassen e.V." (vdek) and the "Knappschaft" these contractors are responsible for conducting the trial.

The Institute for Research in Operative Medicine (IFOM) as part of the University of Witten / Herdecke gGmbH is responsible for the planning, implementation, analysis and publication of the study.

The Private University of Witten / Herdecke takes over the sponsorship of the study project. The duties and responsibilities of the sponsor are transferred to the staff of the Institute for Research in Operative Medicine of University of Witten / Herdecke. The financial support of the clinical study is provided by the manufacturers of the negative pressure wound therapy systems. The task of payment processing and the contractual provisions is taken over by a management company "Gesundheitsforen Leipzig".

Therapy systems used within the treatment arm of the study will be provided by two manufacturers Kinetic Concepts Incorporated (KCI) and Smith \& Nephew Inc. All used treatment systems bear the CE mark and will be used within normal conditions of clinical routine and according to manufacturer's instructions.

This research project is performed because of a decision of the Federal Joint Committee Germany, which states that negative pressure wound therapy can´t be accepted as a standard therapy with full reimbursement by the health insurance companies in Germany. This decision is based on the rapid report and the final report of the Institute for Quality and Efficiency in Health Care, which showed through systematic reviews and meta-analysis of previous study projects that an insufficient state evidence regarding the use of negative pressure wound therapy for the treatment of acute and chronic wounds is existing.

This study evaluates the treatment outcome of the application of a technical medical device, which is based on the principle of negative pressure wound therapy (treatment group 1: Intervention Group) in comparison to standard wound therapy (treatment group 2: Control group) in the treatment of chronic foot wounds after adequate (debridement of avital tissue) wound preparation or amputation wounds resulting from a scheduled amputation below the ankle (talocrural articulation), which are caused in the context of a diabetic foot syndrome.

The clinical trial is designed as a national, multicenter, prospective, randomized controlled superiority study. A blinded evaluation of wound photographs will be performed.

Patients will be randomized 1:1 to the treatment arm: negative pressure wound therapy and the control arm: standard wound therapy.

Patients will be stratified according to assignment to the participating institution (hospital) and by Wagner-Armstrong Stadium.

The inclusion and exclusion criteria are based on the presence of a diagnosis of a diabetic foot wound, the regulatory requirements to the participants in a clinical study and the examination and treatment according to current treatment regulations, evidence-based guidelines and the specifications of the manufacturers of the medical devices.

Only patients meeting all inclusion criteria and no exclusion criterion are allowed to be included into the trial.

The aim of this study is to compare the clinical, safety and economic results of both treatment arms.

The primary endpoints to evaluate the efficacy of negative pressure wound therapy in the treatment of chronic foot wounds caused by a diabetic foot syndrome are both the number of complete wound closure within the maximum treatment period (measured in days) as well as the time until complete wound closure. Complete wound closure should be achieved within the maximum study treatment period of 16 weeks.

In addition, secondary clinical endpoints and safety endpoints, patient-reported outcome endpoints and health economic endpoints are evaluated.

The clinical examination includes parameters that can be used for the analysis of resource use in the inpatient and outpatient care. This includes a comparative analysis of parameters of direct and indirect resource use.

Primarily the perspective of the Statutory Health Insurance is considered. As a secondary perspective the view of society was selected.

Sample size calculation was performed considering results of existing trials, which revealed that a number n = 324 patients must be included in the study in order to carry out the analysis of the primary endpoint "Closure rate".

In due consideration of screening failures, discontinuation of therapy of any cause and losses to Follow-Up a screening of a total of 464 patients must be performed to provide the calculated sample size.The primary efficacy analysis is performed using the intention-to-treat group.

Study results will be provided until the end of 2015 to contribute to the final decision of the Federal Joint Committee Germany regarding the general admission of negative pressure wound therapy as a standard of performance within both medical sectors.

Eligibility criteria: Inclusion Criteria:

* Presence of diabetes mellitus
* Presence of a foot wound (chronic wounds; amputation wounds) Wagner stage 2-4
* Existence of the foot wound for at least 4 weeks
* Signed informed consent form
* Patient's eligibility of NPWT in the opinion of the treating physician

Exclusion Criteria:

* Age \<18 years
* Non-Compliance
* Pregnancy
* Allergies regarding the release of substances from components of each treatment arm
* Severe anemia, wich was not caused by an infection
* Simultaneous participation of patients in another interventional study / previous participation in the same study
* Use of NPWT systems to the study-related foot lesion within a period of 6 weeks prior to study inclusion
* Presence of necrotic tissue with eschar, which can not be removed
* Untreated osteitis or osteomyelitis
* Not examined / unexplored fistula
* Malignancy of the wound
* Exposed: nerves, blood vessels, anastomotic site
* ambulant NPWT of patients receiving anticoagulants (especially heparinization or marcumar therapy) or with otherwise highly impaired clotting function, which have a risk of circulatory relevant bleeding

Primary outcomes:
measure: Number of achieved and confirmed wound closures within the maximum study treatment time
timeFrame: 16 weeks
measure: Time until wound closure within the maximum study treatment time
timeFrame: 16 weeks
Secondary outcomes:
measure: Time until optimal wound bed preparation
timeFrame: 16 weeks
measure: Time until wound closure within the observation period
timeFrame: 6 months
measure: Recurrences
timeFrame: 6 months
measure: Amputations
timeFrame: 16 weeks
measure: Wound size
timeFrame: 16 weeks
measure: Wound tissue qualities
timeFrame: 16 weeks
measure: Number of complete wound closures within the observation period
timeFrame: 6 months
measure: Wound-related pain (Numeric Rating Scale)
timeFrame: 16 weeks
measure: Quality of Life questionaire (EQ-5D)
timeFrame: 6 months
measure: Direct costs
timeFrame: within a maximum treatment time of 16 weeks or until end of therapy
measure: Indirect costs
timeFrame: within a maximum treatment time of 16 weeks or until end of therapy
measure: Serious adverse events
timeFrame: 6 months
measure: Adverse Events
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Bad Mergentheim
country: Germany
facility: Diabetes Klinik GmbH & Co KG
city: Berlin
country: Germany
facility: Evangelisches Krankenhaus, Königin Elisabeth Herzberge gGmbH
city: Berlin
country: Germany
facility: Franziskus-Krankenhaus Berlin, Abteilung für Innere Medizin
city: Bielefeld
country: Germany
facility: Klinikum Bielefeld, Klinik für Allgemeine und Innere Medizin
city: Bogenhausen
country: Germany
facility: Gerhard Rothenaicher, Facharzt für Chirurgie, München Bogenhausen
city: Bottrop
country: Germany
facility: Knappschaftskrankenhaus Bottrop Klinik für Gefäßchirurgie
city: Buchloe
country: Germany
facility: Tagesklinik Buchloe
city: Darmstadt
country: Germany
facility: Klinikum Darmstadt, Gefäß- und Endovascularchirurgie
city: Dortmund
country: Germany
facility: Marienhospital Dortmund-Hombruch, Klinik für Innere Medizin / Diabetologie
city: Duisburg
country: Germany
facility: Diabetische Schwerpunktpraxis
city: Döbeln
country: Germany
facility: Klinikum Döbeln
city: Flensburg
country: Germany
facility: Malteser Krankenhaus - St. Franziskus-Hospital, Medizinische Klinik I, Abt. f. Diabetologie
city: Frankfurt (Oder)
country: Germany
facility: Klinikum Frankfurt (Oder), Klinik für Gefäßchirurgie
city: Frankfurt am Main
country: Germany
facility: Goethe Universität Frankfurt am Main, Klinik für Gefäß- und Endovascularchirurgie
city: Frankfurt
country: Germany
facility: Bürgerhospital, Klinik für Diabetologie und Ernährungsmedizin
city: Freital
country: Germany
facility: Weißeritztal-Kliniken GmbH Klinik für Gefäßchirurgie-, vaskuläre und endovaskuläre Chirurgie, Phlebologie
city: Geislingen
country: Germany
facility: Helfenstein Klinik Geislingen, Allgemein- und Viszeralchirurgie
city: Hamburg
country: Germany
facility: Asklepios Kliniken Harburg
city: Hamburg
country: Germany
facility: ASKLEPIOS Westklinikum Hamburg GmbH
city: Hannover-Langenhagen
country: Germany
facility: Paracelsusklinik am Silbersee, Wundzentrum Hannover
city: Heide
country: Germany
facility: Westküstenklinikum Heide, Klinik für Visceral- und Gefäßchirurgie
city: Karlsruhe
country: Germany
facility: Städtisches Klinikum Karlsruhe GmbH
city: Krefeld
country: Germany
facility: Alexianer Krankenhaus Krefeld GmbH, Klinik für Allgemein-, Visceral- und Thoraxchirurgie
city: Köln
country: Germany
facility: Gemeinschaftspraxis Schlotmann - Hochlenert - Zavaleta - Haberstock
city: Köln
country: Germany
facility: Chirurgische Praxisgemeinschaft am Bayenthalgürtel, Praxis Dr. med. Gerald Engels
city: Köln
country: Germany
facility: Krankenhaus Porz am Rhein, Klinik für Gefäßchirurgie
city: Leverkusen
country: Germany
facility: St. Remigius Krankenhaus Opladen
city: Ludwigsburg
country: Germany
facility: Klinikum Ludwigsburg, Klinik für Gefäßchirurgie, vaskuläre und endovaskuläre Chirurgie
city: Ludwigshafen
country: Germany
facility: Diabetologikum Ludwigshafen, Diabetes-Schwerpunktpraxis
city: Lübeck
country: Germany
facility: Uniklinik Lübeck, Klinik für Allgemeine Chirurgie
city: Mönchengladbach
country: Germany
facility: Kliniken Maria Hilf GmbH
city: München
country: Germany
facility: Städt. Klinikum Bogenhausen
city: Münster
country: Germany
facility: Institut für Diabetesforschung Münster GmbH
city: Neunkirchen
country: Germany
facility: Städtisches Klinikum Neunkirchen gGmbH
city: Oberhausen
country: Germany
facility: Gemeinschaftspraxis Drs. Alter, Heim, Pourhassan
city: Offenburg
country: Germany
facility: Ortenau Klinikum Offenburg, Klinik für Allgemein-, Viszeral- und Gefäßchirurgie
city: Quedlinburg
country: Germany
facility: Klinikum Dorothea Christiane Erxleben Quedlinburg GmbH, Klinik für Allgemein-, Visceral- und Gefäßchirurgie
city: Radolfzell am Bodensee
country: Germany
facility: Hegau-Bodensee Klinikum Radolfzell (HBK), Klinik für Innere Medizin
city: Saalfeld
country: Germany
facility: Thüringen Kliniken "Georgius Agricola", Klinik für Gefäßchirurgie
city: Siegen
country: Germany
facility: St. Marienkrankenhaus Siegen gGmbH, Klinik für Gastroenterologie
city: Werl
country: Germany
facility: Mariannen-Hospital Werl, Abteilung für Chirurgie
city: Wiesbaden
country: Germany
facility: HSK - Dr. Horst Schmidt Kliniken GmbH
Study officials:
affiliation: Witten Herdecke University
name: Dörthe Seidel
role: PRINCIPAL_INVESTIGATOR
References:
citation: Seidel D, Mathes T, Lefering R, Storck M, Lawall H, Neugebauer EA. Negative pressure wound therapy versus standard wound care in chronic diabetic foot wounds: study protocol for a randomized controlled trial. Trials. 2014 Aug 27;15:334. doi: 10.1186/1745-6215-15-334.
citation: Seidel D, Storck M, Lawall H, Wozniak G, Mauckner P, Hochlenert D, Wetzel-Roth W, Sondern K, Hahn M, Rothenaicher G, Kronert T, Zink K, Neugebauer E. Negative pressure wound therapy compared with standard moist wound care on diabetic foot ulcers in real-life clinical practice: results of the German DiaFu-RCT. BMJ Open. 2020 Mar 24;10(3):e026345. doi: 10.1136/bmjopen-2018-026345.
citation: Seidel D, Lefering R; DiaFu study group. NPWT resource use compared with standard moist wound care in diabetic foot wounds: DiaFu randomized clinical trial results. J Foot Ankle Res. 2022 Sep 30;15(1):72. doi: 10.1186/s13047-022-00569-w.