The Effect of Nitroglycerin Ointment, Fluorescent Angiography, and Incisional Negative Pressure Wound Therapy on Mastectomy Skin Flap Perfusion-Related Problems

This is a randomized study using a variety of techniques to compare and examine blood flow to the remaining skin after mastectomy. All treatments being used are considered standard of care and are not experimental. The objective is to compare the techniques and the incidence of perfusion related problems in patient's undergoing mastectomy with immediate breast reconstruction.

Study Overview

• Status: Terminated
• Conditions: Perfusion; Complications
• Intervention / Treatment: Other: No treatment; Drug: Nitroglycerin; Device: Negative Pressure Wound Therapy/ Wound VAC; Other: Fluorescent Angiography with indocyanine-green (not to exceed 5mg/kg)

Detailed Description

This study's aim is to evaluate and compare a variety of interventions and their effect on the incidence of perfusion related problems in patients with breast cancer undergoing mastectomy and implant-based immediate breast reconstruction (IBR). The ability to identify, prevent and treat these perfusion related problems can help maximize aesthetic results after breast surgery, improve patient satisfaction with both mastectomy and breast reconstruction, and reduce healthcare cost associated with mastectomy and reconstruction complications.The study team will perform a randomized pilot study comprised of eight groups. All of these groups employ accepted techniques, medications and dressings and therefore are not experimental.

Group 1: Breast skin after mastectomy will be clinically examined by the surgeon to determine if there is adequate blood flow to the skin to allow safe coverage of the breast implant. No dye study, ointment, or vacuum dressing will be applied to the breast after implant placement.

Group 2 - Breast skin after mastectomy will be clinically examined by the surgeon, and nitroglycerin (NTG) cream will be applied to the breast skin after implant placement. This cream does not have systemic effects but may improve blood flow to the remnant breast skin after mastectomy.

Group 3 - Breast skin after mastectomy will be clinically examined by the surgeon, and an incisional vacuum-assisted dressing (iVAC) will be placed over the breast incisions after implant placement, which may improve blood flow to the skin and help wound healing.

Group 4 - Breast skin after mastectomy will be clinically examined by the surgeon, and both NTG cream will be applied to the breast skin and an iVAC will be placed over the incisions after implant placement.

Group 5 - Blood flow to breast skin after mastectomy will be examined using a fluorescent dye study called fluorescent angiography (FA) to determine if there is adequate blood flow to the skin to allow safe coverage of the breast implant. No further intervention will be used after implant placement.

Group 6 - Blood flow to breast skin breast skin will be examined using FA, and NTG cream will be applied to the skin after the implant is placed.

Group 7 - Blood flow to breast skin breast skin will be examined using FA, and an iVAC will be placed over breast skin incisions after the implant is placed.

Group 8 - Blood flow to breast skin breast skin will be examined using FA, and both NTG cream and iVAC will be used as interventions after the implant is placed.

The dosage of indocyanine-green (IC-green) to be used for assessment of mastectomy flaps will be in 10 mg boluses, not to exceed 5 mg/kg.

Nitro-Bid® (nitroglycerin ointment, 2%) at a dose of 45 mg (equal to 7.5 cm on the measuring strip provided with packaging) will be used. The paste will be applied to remnant breast skin after skin closure and surgical dressings placed over top.

Incisional negative pressure wound therapy will consist of a standard sponge dressing with adhesive drape, either Ioban® 2 (3M ™) or KCI-V.A.C.® Drape (KCI®), to continuous suction at 125 mm Hg while the patient is in hospital and not to exceed 4 days.

A physician will see the subjects on a regular weekly basis for up to 30 days once the procedure has been completed. These clinical visits are standard of care and the subject's health and well-being will be monitored rigorously during these visits. If during any of these visits, the physician deems a therapy necessary to prevent impairment/damage and improve well-being, the subject will be treated appropriately.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patients must be female.
• Patients must be between the ages of 18 and 99 years.
• Patients must undergo mastectomy with our attending breast oncology surgeons followed by possible implant-based immediate breast reconstruction (IBR) performed by our attending plastic surgeons at WFBMC.
• Patients must have the ability to understand and the willingness to sign an IRB-approved informed consent document.

Exclusion Criteria:

• Patients who are under the age of 18 or over the age of 99.
• Patients who are undergoing mastectomy without immediate breast reconstruction including immediate breast reconstruction with autologous tissue (or combination of autologous tissue with tissue expanders or implants), or patients with a history of mastectomy presenting for delayed breast reconstruction.
• Patients with pre-existing conditions in which use of indocyanine-green is contraindicated or must be used with caution, including those with a history of allergy to iodides or iodinated dye, those with chronic kidney disease, those with hepatic failure or cirrhosis of the liver, and females who are nursing, pregnant, or may become pregnant.
• Pregnant women are excluded from this study because pregnancy precludes immediate breast reconstruction in our patient population.
• Patients with pre-existing conditions in which use of nitroglycerin paste is contraindicated, including those with a history of cardiac insufficiency, hypotension, sensitivity to nitrites, severe liver impairment, glaucoma, hyperthyroidism, recent head trauma, severe anemia, or taking certain medication (i.e. alteplase, aspirin, beta-blocker, calcium channel blocker, diuretics or thiazides).
• Patients with pre-existing conditions in whom use of incisional negative pressure wound therapy is contraindicated including those with evidence of surgical site infection ( i.e. erythema, purulent drainage), clinical signs of hematoma (i.e. wound swelling, fluctuance, blood drainage), history of persistent cancer, exposed blood vessel on site of proposed therapeutic use, or sensitivity to acrylics and adhesives.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Group 1; Breast skin after mastectomy will be clinically examined by the surgeon to determine if there is adequate blood flow to the skin to allow safe coverage of the breast implant. No treatment, including dye study, ointment, or vacuum dressing will be applied to the breast after implant placement.	Other: No treatment; Patient's will be randomized into one of eight groups and receive the intended treatment specified for that particular group. Groups 1 will include no treatment.
Active Comparator: Group 2; Breast skin after mastectomy will be clinically examined by the surgeon, and nitroglycerin (NTG) cream will be applied to the breast skin after implant placement. This cream does not have systemic effects but may improve blood flow to the remnant breast skin after mastectomy.	Drug: Nitroglycerin; Patient's will be randomized into one of eight groups and receive the intended treatment specified for that particular group. Groups 2,4,6, and 8 will include Nitroglycerin cream.; Other Names: Nitro-Bid 2%
Active Comparator: Group 3; Breast skin after mastectomy will be clinically examined by the surgeon, and an incisional vacuum-assisted dressing (iVAC) will be placed over the breast incisions after implant placement, which may improve blood flow to the skin and help wound healing.	Device: Negative Pressure Wound Therapy/ Wound VAC; Patient's will be randomized into one of eight groups and receive the intended treatment specified for that particular group. Groups 3,4,7,and 8 will receive iVAC therapy.; Other Names: iVAC
Active Comparator: Group 4; Breast skin after mastectomy will be clinically examined by the surgeon, and both NTG cream will be applied to the breast skin and an iVAC will be placed over the incisions after implant placement.	Drug: Nitroglycerin; Patient's will be randomized into one of eight groups and receive the intended treatment specified for that particular group. Groups 2,4,6, and 8 will include Nitroglycerin cream.; Other Names: Nitro-Bid 2%; Device: Negative Pressure Wound Therapy/ Wound VAC; Patient's will be randomized into one of eight groups and receive the intended treatment specified for that particular group. Groups 3,4,7,and 8 will receive iVAC therapy.; Other Names: iVAC
Active Comparator: Group 5; Blood flow to breast skin after mastectomy will be examined using a fluorescent dye study called fluorescent angiography (FA) to determine if there is adequate blood flow to the skin to allow safe coverage of the breast implant. No further intervention will be used after implant placement.	Other: Fluorescent Angiography with indocyanine-green (not to exceed 5mg/kg); Patient's will be randomized into one of eight groups and receive the intended treatment specified for that particular group. Groups 5,6,7,and 8 will receive angiography.
Active Comparator: Group 6; Blood flow to breast skin breast skin will be examined using FA, and NTG cream will be applied to the skin after the implant is placed.	Drug: Nitroglycerin; Patient's will be randomized into one of eight groups and receive the intended treatment specified for that particular group. Groups 2,4,6, and 8 will include Nitroglycerin cream.; Other Names: Nitro-Bid 2%; Other: Fluorescent Angiography with indocyanine-green (not to exceed 5mg/kg); Patient's will be randomized into one of eight groups and receive the intended treatment specified for that particular group. Groups 5,6,7,and 8 will receive angiography.
Active Comparator: Group 7; Blood flow to breast skin breast skin will be examined using FA, and an iVAC will be placed over breast skin incisions after the implant is placed.	Device: Negative Pressure Wound Therapy/ Wound VAC; Patient's will be randomized into one of eight groups and receive the intended treatment specified for that particular group. Groups 3,4,7,and 8 will receive iVAC therapy.; Other Names: iVAC; Other: Fluorescent Angiography with indocyanine-green (not to exceed 5mg/kg); Patient's will be randomized into one of eight groups and receive the intended treatment specified for that particular group. Groups 5,6,7,and 8 will receive angiography.
Active Comparator: Group 8; Blood flow to breast skin breast skin will be examined using FA, and both NTG cream and iVAC will be used as interventions after the implant is placed.	Drug: Nitroglycerin; Patient's will be randomized into one of eight groups and receive the intended treatment specified for that particular group. Groups 2,4,6, and 8 will include Nitroglycerin cream.; Other Names: Nitro-Bid 2%; Device: Negative Pressure Wound Therapy/ Wound VAC; Patient's will be randomized into one of eight groups and receive the intended treatment specified for that particular group. Groups 3,4,7,and 8 will receive iVAC therapy.; Other Names: iVAC; Other: Fluorescent Angiography with indocyanine-green (not to exceed 5mg/kg); Patient's will be randomized into one of eight groups and receive the intended treatment specified for that particular group. Groups 5,6,7,and 8 will receive angiography.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Soft Tissue Ischemia/Loss	Number of partial and full thickness soft tissue defects identified postoperatively in clinic follow up	Up to 30 days
Number of Participants With Surgical Site Infection	Number of Participants with soft tissue cellulitis or abscess identified postoperatively either clinically or with wound culture	Up to 30 days
Number of Participants With Delayed Wound Healing	manifesting as suture dehiscence and opening of an incisional wound	Up to 30 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Operative Intervention Secondary to Perfusion Related Problems	Up to 30 days
Number of Participants Requiring Outpatient Prescription for Antibiotics or Requiring Hospital Admission for IV Antibiotics	Up to 30 days
Number of Participants Requiring Wound Care Management Modalities for Treatment of Delayed Wound Healing Complications	up to 30 days

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Investigators: Principal Investigator: Ivo A Pestana, MD, WFUHS

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2018
• Primary Completion (Actual): March 12, 2019
• Study Completion (Actual): March 12, 2019

Study Registration Dates

• First Submitted: October 19, 2018
• First Submitted That Met QC Criteria: October 19, 2018
• First Posted (Actual): October 23, 2018

Study Record Updates

• Last Update Posted (Actual): May 21, 2020
• Last Update Submitted That Met QC Criteria: May 8, 2020
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Breast Cancer; breast reconstruction; Implant Complication
• Additional Relevant MeSH Terms: Vasodilator Agents; Nitroglycerin
• Other Study ID Numbers: IRB00038262

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No