Treatment Study of Negative Pressure Wound Therapy for Diabetic Foot Wounds

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.

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