Negative Pressure Wound Therapy as a Drug Delivery System

Study Overview
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Brief Summary
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The investigators plan a randomized clinical trial of 150 patients with infected diabetes-related lower extremity wounds to compare the clinical and economic effectiveness of negative pressure wound therapy with continuous irrigation and negative pressure wound therapy without irrigation.

Detailed Description
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The investigators will enroll 150 patients from two centers: The University of Texas Southwestern University Hospital and Parkland Hospital. The investigators will screen and enroll patients with wounds in the inpatient setting. Patients will be randomized to receive traditional NPWT or NPWT with continuous irrigation while they are hospitalized. The average hospitalization for patients that receive NPWT is 13.3 days. Patients that do not have their wound surgically closed during hospitalization will be discharged with negative pressure wound therapy for up to a total of four weeks of therapy. After discharge from the hospital, subjects will be seen twice weekly by home health, and will be evaluated in clinic every 7 days (±7 days) up to a total of 16-week period or until 30 days after the wound heals. Study Procedures: Screening Procedures Review and sign the Informed Consent and HIPAA Authorization The study doctor will review the inclusion and exclusion criteria Demographics (such as age, gender, race or ethnicity) Physical exam Sitting blood pressure and pulse Height and weight Collection of the medical and surgical history Collection of the history of the wound Wound assessment(s)/Debridement - various tests and measurements to assess the sensation (feeling) and circulation (blood flow) in the subject's feet and lower legs. None of these tests are invasive (using needles), uncomfortable or have risks greater than standard care. Wound imaging - photographs and images of the subject's wound using acetate tracings, a digital camera and an ARANZ camera (a special type of camera that uses computer software to calculate the volume of the wound) Hyperspectral imaging Vascular/Neurological evaluation Results of standard-of-care laboratory tests including a white blood cell count, blood chemistry (tests to see how well organs, such as the liver and kidneys are working), and blood glucose. Results of a serum pregnancy test (standard care for women of child-bearing potential as part of pre-op labs) will also be collected. About 2 tablespoons of blood will be drawn for these tests. Collection of a list of the subject's current medications, including prescriptions, over-the-counter medications, supplements and herbals. This visit will last about 2 hours. If the subject qualifies for the study, they will participate in the following procedures: Group Assignment If the researchers believe the subject can take part in this study, s/he will be assigned randomly (like a flip of a coin) to receive one of the following therapies: Negative Pressure Wound Therapy with Irrigation Negative Pressure Wound Therapy without Irrigation The group is assigned randomly (like flipping a coin). The sponsor or researchers do not know in advance what group assignment each subject will receive. Neither the subject nor the researchers will be allowed to choose which group s/he is assigned to. Study Intervention The subject will receive either: Cardinal Pro +Simultaneous Irrigation (NPWTi) - Negative Pressure Wound Therapy with Prontosan®, or Cardinal Pro (NPWT) Therapy (without Prontosan®) Assigned therapy will continue in the hospital until the physician determines that the wound is ready for closure. If the subject's wound is healing, study therapy will be discontinued and standard dressings will be applied. If surgical closure is needed, the subject will return to the Operating Room for a procedure to close the wound. If the wound is not ready for closure during the hospital stay, subjects will continue NPWT at home for the remainder of the 4 weeks of treatment. NPWT at home will be without irrigation (KCI VAC Via®). Procedures and Evaluations during the Research The study therapy will only be given while the subject is in the hospital. S/he will continue the therapy for up to 4 weeks or until the wound is closed. Once the therapy is stopped s/he will continue to be followed by the study doctor. After the subject is released from the hospital s/he will need to see the study doctor Every 7 days (±7 days). If the subject's wound does not heal before 56 days after his/her first surgery then s/he will no longer be taking part in the study. The study doctor will continue to check the wound. If the wound closes, s/he will see the study doctor 30 days later to have the closed wound checked. 12 Month Extension: After the end of the defined study period, the patients will be followed observationally by their electronic medical records for 12 months as it would not be feasible to ask them to return for an in-person evaluation as: patients have moved, no longer have correct contact information, as well as it would create a financial hardship on the patients to return for further visits. In order to more appropriately determine long term results from participation, a longer period of time of follow up is necessary. Related outcomes that we would like to follow over a 12-month duration are incidence of new foot ulcerations, re-ulceration of a previously healed foot wound, healing and time to healing of patients who took longer than the current study allows, duration of antibiotics received for foot infections, re-admissions to the hospital, need for subsequent surgery, amputation, loss of limb, and death. This expanded follow up period would provide valuable information to the long-term outcomes and complications of this high risk population and will help direct how future efforts may be better focused to reduce complications and improve outcomes.

Official Title
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Negative Pressure Wound Therapy as a Drug Delivery System

Conditions
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Diabetic Foot Ulcers

Intervention / Treatment
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* Device: Cardinal Pro +Simultaneous Irrigation (NPWTi)
* Device: Cardinal Pro (NPWT) Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of diabetes mellitus Men/women ≥21 years old Foot or ankle wounds sized 5 cm2 -100 cm2 ABI≥0.5 or toe pressures >30 mmHg Exclusion Criteria: Active Charcot arthropathy Unable to use NPWT at home Untreated bone or soft tissue infection Unable to keep research appointments Active alcohol or substance abuse

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cardinal Pro + Irrigation (NPWTi)<br>Negative Pressure Wound Therapy with Irrigation: Quantum™ +Simultaneous Irrigation (NPWTi) - Negative Pressure Wound Therapy with Prontosan® Intervention is receiving the Cardinal Vac with Irrigation | Device: Cardinal Pro +Simultaneous Irrigation (NPWTi)<br>* NPWT with low volume irrigation (15 cc/hr) with 1% polyhexanide biguanide (PHMB), Prontosan®<br>* Other names: • Negative Pressure Wound Therapy with Irrigation;|
| Active Comparator: Cardinal Pro (NPWT) Therapy<br>Negative Pressure Wound Therapy without Irrigation: Quantum™ (NPWT) -Negative Pressure Wound Therapy (without Prontosan®) Intervention is receiving the Cardinal Vac without Irrigation | Device: Cardinal Pro (NPWT) Therapy<br>* NPWT 125 mm Hg continuous pressure with foam interface<br>* Other names: • Negative Pressure Wound Therapy without Irrigation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Achieved Complete Healing or Coverage of the Study Wound | How many wounds fully healed in 16 weeks. Healing defined as fully epithelialized skin with no drainage. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Adverse Events of Participants | Total number of adverse events, including new foot ulcer formation, all-cause hospital readmission, and foot-related hospital readmission. | 16 Weeks | 
| Number of Participants With Wound Dehiscence After Hospital Discharge | Dehiscence is defined as any part of a surgically closed wound that failed to heal when sutures were removed. | 16 weeks |