Clinical trial NCT03069885: iNPWT in Immediate Breast Reconstruction
Official title: Incisional Negative Pressure Wound Therapy (Prevena™) vs. Conventional Post-operative Dressing After Immediate Breast Reconstruction; a Randomized Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Breast Neoplasm Female
Mammaplasty
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2017-03-03
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The project is conducted as a randomized controlled trial. Patients included in the study will be randomized to either conventional post-operative dressing or PrevenaTM iNPWT treatment. Patients are allocated in a 1:1 ratio, with 30 patients treated with PrevenaTM and 30 patients treated with conventional post-operative dressing.
Primary purpose: TREATMENT

Brief summary: Due to the Danish breast cancer-screening programme and the increased use of genetic counselling, Danish women are being diagnosed with breast cancer, or a high lifetime risk of developing breast cancer, at a younger age than previously. An increasing proportion of these women pursue an immediate breast reconstruction, where the breast is removed and reconstructed in a single surgical procedure.

As some of these women will need to undergo adjuvant cancer therapy after their breast surgery, fast recovery is essential in order for the adjuvant therapy not to be delayed. With the development of new surgical techniques, the complication rate to the immediate breast reconstructions has improved. However, wound-healing issues remain one of the most common complications to the surgery with the possibility of delaying the adjuvant therapy and diminish the aesthetic result.

Incisional negative pressure wound therapy (iNPWT), is a new approach for surgical site closure. Recently, iNPWT has shown promising results in lowering post-operative complications, including wound-healing issues, in other surgical settings. However, iNPWT has still not been studied in an immediate breast reconstructive setting.

The current randomized controlled clinical study will investigate if an iNPWT system, is able to provide women seeking an immediate breast reconstruction with faster healing and superior aesthetic results compared to the conventional post-operative wound dressings used today. The investigators plan to include 60 women, randomized in a 1:1 ratio between iNPWT or conventional wound dressing. The primary outcome measure is the time until removal of the surgical drains, which corresponds to the healing progression. Secondarily, complications to the surgery, assessment of the scar (measured using the Patient and Observer Scar Assessment Scale) and patient reported satisfaction with the reconstruction (assessed using the BREAST-Q questionnaire) will be performed. Included patients are examined pre-operatively, and at the routine controls at four weeks and four months post operatively.

The results from the current study will elucidate if iNPWT aids wound healing after immediate breast reconstruction, which would lead to fewer patients experiencing delays before their adjuvant therapy. Furthermore, the results from the aesthetic satisfaction will elucidate if iNPWT provides the patients with a better self-reported aesthetic result.

Detailed description: Incisional negative pressure wound therapy (Prevena™) vs. conventional post-operative dressing after immediate breast reconstruction; a randomized controlled clinical trial.

• Introduction

Over the last 60 years, there has been a steady rise in the incidence of breast cancer in Denmark. Due to the Danish breast cancer screening program and the increasing use of genetic counseling, patients are diagnosed with breast cancer, pre-cursors hereof, or an increased lifetime risk of breast cancer at an earlier age than previously. In women with high estimated risk of breast cancer, current studies indicate a reduced lifetime risk of cancer, and thereby increased survival, when undergoing a risk reducing mastectomy. Therefore, Danish women may choose to undergo a risk reducing mastectomy, if they have a estimated lifetime risk of breast cancer at 30% or above.

At the Department of Plastic and Breast Surgery, Aarhus University Hospital, Denmark, there has been a rise in the number of immediate breast reconstructions performed, currently counting approximately 200 per year. This increase is partly due to the increasing number of prophylactic risk reducing mastectomies, as well as an increasing number of women choosing immediate breast reconstruction when diagnosed with Ductal Carcinoma In-Situ (DCIS).

As some of these women will need to undergo adjuvant cancer therapy after their breast surgery, fast recovery is essential in order for the adjuvant therapy to not be delayed.

Women undergoing surgery at a younger age, will presumably live for a longer time, with possible complications of the immediate breast reconstruction. Therefore, a good result at the first surgery and fast rehabilitation, are of essential importance for these women's recovery and quality of life.

The immediate breast reconstruction, holds several benefits compared to mastectomy and subsequent delayed breast reconstruction. Benefits such as rapid return to work, low complication rate, good aesthetic outcome, and the need for only one surgery, but the surgery is not free of complications. The complication rate in immediate breast reconstruction, is reported in the range of 3,9% to 14,8 %, with the most frequent complications being skin necrosis, surgical site infections (SSI), implant loss and haematoma/seroma.

Incisional negative pressure wound therapy (iNPWT), is a new approach for surgical site closure using negative pressure wound therapy (NPWT). Recently, PrevenaTM have been approved as an iNPWT-system applied at the end of surgery, while still in a sterile environment. PrevenaTM consist of a sponge foam with a bactericidal silver lining, dressed with an adherent film, connected to a vacuum device, producing a vacuum of 125 mm Hg. The PrevenaTM foam and dressing is placed over the suture line, and is recommended to be kept in place for a continuous period lasting between 2 and 7 days.

iNPWT is based on the principles behind NPWT, most known as vacuum assisted closure (V.A.C.), which is well described in the literature.

NPWT has been shown to be an efficient way of treating chronic wounds, by increasing blood flow and formation of granulation tissue, stimulate cell proliferation and angiogenesis, decrease bacterial count, reduce oedema, improve wound closure rates, collagen organization and wound maturation in animal- and clinical-studies.

Furthermore, recently iNPWT has shown promising results in lowering post-operative complications, with lower rate of surgical site infection, lower incidence of wound dehiscence, and lower loss of split thickness skin grafts.

In an experimental porcine setup, indications of increased lymph clearance with lower production of seroma/hematoma has been shown when using iNPWT. Additionally, in a biomechanical analysis, Wilkes et al. found evidence of reduced lateral stress on wounds, which in theory, could lead to faster closure and improved scar aesthetics.

Overall, iNPWT has been shown to reduce several of the most frequent complications that may occur following an immediate breast reconstruction. However, in an immediate breast reconstructive setting, iNPWT has not yet been studied, and in breast surgery in general, there is only limited data on the use of NPWT and iNPWT.

The current study aims to investigate whether PrevenaTM provides a superior post-operative wound treatment, when compared to conventional treatment, for women undergoing a prophylactic or therapeutic mastectomy with an immediate breast reconstruction.

• Hypothesis

iNPWT, administrated by PrevenaTM, will reduce the post-operative complications in patients undergoing immediate breast reconstruction, compared to conventional post-operative dressing.

• Aim

The aim of the current study is to evaluate whether iNPWT provides superior wound treatment for patients undergoing an immediate breast reconstruction, compared to treatment with conventional post-operative dressing. The results from this study will possibly help to minimize the complication rate and increase the patient satisfaction, by finding the optimal wound treatment for immediate breast reconstructions and thereby contributing to a faster recovery, for women who undergo this procedure.

• Methods

The project is conducted as a randomized controlled trial. Patients included in the study will be randomized to either conventional post-operative dressing or PrevenaTM iNPWT treatment. Patients are allocated in a 1:1 ratio, with 30 patients treated with PrevenaTM and 30 patients treated with conventional post-operative dressing.

* Study population

  60 patients admitted for immediate breast reconstruction at the Department of Plastic Surgery, Aarhus University Hospital, will upon informed consent be offered participation in this prospective, randomized study using two types of post-operation dressing after the breast reconstruction surgery
* Risks, side effects and disadvantages

As with all surgery, there is a risk of wound infection, blood clots and altered sensation in the operated area. This can lead to antibiotic treatment, or where appropriate, a second surgery to stop bleeding or remove damaged tissue. These risks are, however, associated with the breast reconstruction itself, and not associated with participating in the research project.

PrevenaTM have been approved and used internationally as a post-operative dressing since 2010. PrevenaTM is well described in the medical literature, achieving good results compared to conventional post-operative dressing, showing fewer, or the same amount of complications. The risks for the patients choosing to participate in the project are thus solely related to the breast reconstruction itself, and not to the participation in the research project.

• Economics

Initiators of this project are the Department of Plastic and Brest Surgery, Aarhus University Hospital. All costs of the investigated post-surgical wound treatment (PrevenaTM or conventional post-operative treatment) are held by the Department of Plastic and Brest Surgery, Aarhus University Hospital. Participating patients are not given any reimbursement. Patients may, however, apply for reimbursement to cover documented travel expenses, in regards to the regulations of the Central Denmark Region.

The salary for the scientific personnel, and cost of materials and conferences will be sought covered by external funding from private and/or governmental funds. Funding will solely be sought from foundations and scholarships, where the benefactors do not have a financial interest in the outcome of the study. Furthermore, funding will only be sought from sources, where the research project can remain independent from the contributor.

• Publication

Positive, negative, as well as inconclusive results are expected to be published in a peer-reviewed international journal with interest in the field. Furthermore, the results are expected to be presented at a national or international conference in plastic and reconstructive surgery.

• Ethical considerations

It is expected that the number of women seeking an immediate breast reconstruction will increase. The proposed study will aid in finding the most optimal wound dressing following this surgery. Conducting studies that help bring down the complication rates for these types of surgery is of utmost importance, both for the individual patient undergoing the surgery and in a socio-economic setting.

All of the patients invited to participate in this study has been evaluated by experienced breast and plastic surgeons to be best suited with an immediate breast reconstruction with implant.

PrevenaTM, or iNPWT, have shown good results in previous studies in other types of surgery, showing none or only minor complications. The general treatment, using steri strips, has been used for many years as the primary choice.

As the investigators expect fewer or the same amount of complications when using PrevenaTM, there is no predictable disadvantage for the individual patient in regards to participating in the study.

The patients' privacy, physical and mental integrity and the Danish law concerning the processing of personal data will be respected. Furthermore, the research project will be carried out in accordance with the Helsinki Declaration II.

The project is approved by the Central Denmark Regional Committee on Health Research Ethics, see appendix 2 (in Danish) and registered at the Central Denmark Regions joint application for the Danish Data Protection Agency, see Appendix 3 (in Danish).

• Perspectives

The results from the current study will elucidate if iNPWT aids wound healing after immediate breast reconstruction, which would lead to fewer patients experiencing delays before their adjuvant therapy. Furthermore, the results from the aesthetic satisfaction will elucidate if iNPWT provides the patients with a better self-reported aesthetic result.

Faster healing could potentially result in a shorter hospital stay. At the Department of Plastic and Breast Surgery, Aarhus University Hospital, the approximate cost per hospitalization day is 4000 Danish kroner (DKK). With a price of 975 DKK., the PrevenaTM-device could be a potential economical benefit, with an average reduction in hospitalization time by just a single day. Finally, the potential cost savings do to fewer post-operative complications, should be held in consideration.

All in all, the results from the current study may provide the increasing number of women undergoing an immediate breast reconstruction with a shorter hospital stay, a better breast reconstructive result and faster adjuvant therapy.

Eligibility criteria: 60 patients admitted for immediate breast reconstruction at the Department of Plastic Surgery, Aarhus University Hospital, will upon informed consent be offered participation in this prospective, randomized study using two types of post-operation dressing after the breast reconstruction surgery.

Inclusion Criteria:

* Patient deemed best suited with an immediate breast reconstruction using implant by the consultant plastic- and breast surgeon.
* Patient is older than 18 years of age.
* Patient understand enough Danish to comprehend the given information and to complete the study questionnaires.

Exclusion Criteria:

* Current smokers (patients not having paused for a minimum of four weeks prior to surgery)
* Non-eligible patients, as assessed by the operating surgeon
* High level of co-morbidity, as assessed by operating surgeon or anaesthesiologist
* Allergic to band-aids.

Primary outcomes:
measure: Drain time
timeFrame: 1-14 days after surgery
Secondary outcomes:
measure: Surgical site infection
timeFrame: 1-30 days after surgery
measure: Skin necrosis
timeFrame: 1-30 days after surgery
measure: Hospitalization time
timeFrame: 1-30 days after surgery
measure: Patient and observer assessment of the scars
timeFrame: 4 weeks and 4 month after surgery
measure: Patient satisfaction and quality of Life
timeFrame: 1 week before surgery until 4 months after surgery
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital, NBG
Study officials:
affiliation: University of Aarhus and Aarhus University Hospital
name: Tine E Damsgaard, MD, Phd.
role: STUDY_DIRECTOR
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