Indocyanine Green for Perfusion Assessment of DIEP Flaps (FAFI)

Indocyanine Green for Perfusion Assessment of DIEP Flaps: A Dutch Multicenter Randomized Controlled Trial

Currently during DIEP flap reconstruction, the perfusion of the flap is assessed by the clinical view of the surgeon. Identification of demarcated ischemic zones of the DIEP flap could be optimized by using fluorescence imaging with indocyanine green (ICG) in order to lower the rate of fat necrosis. This study evaluates whether intraoperative perfusion assessment with ICG fluorescence imaging causes a lower rate of fat necrosis compared to conventional intraoperative clinical evaluation of DIEP flaps.

Study Overview

• Status: Recruiting
• Conditions: Fat Necrosis
• Intervention / Treatment: Diagnostic test: Near-infrared fluorescence imaging of perfusion

Detailed Description

Rationale: Autologous breast reconstruction after mastectomy due to cancer or prophylactically due to genetically increased risk is frequently performed. A complication that may occur after a deep inferior epigastric artery (DIEP) reconstruction is the occurrence of fat necrosis in the transplanted flap due to ischemia (reperfusion injury). Identification of deep inferior epigastric artery perforators and identification of demarcated ischemic zones of the DIEP flap can be optimized by using fluorescence imaging with indocyanine green (ICG), as has been demonstrated in previous studies. This could result in less fat necrosis, less partial flap loss, and other complications. A randomized controlled trial would be the best study design to assess the value of ICG in determining the perfusion of DIEP flaps, thereby reducing the occurrence of fat necrosis and other complications.

Objective: To determine whether fluorescence imaging using ICG for the assessment of DIEP flap perfusion during surgery decreases the occurrence of fat necrosis compared to standard intraoperative clinical assessment of DIEP flap perfusion.

Study design: This is a two-armed randomized controlled trial:

• interventional arm: evaluation of flap perfusion based on 1) clinical parameters, and 2) fluorescence imaging using ICG
• conventional arm: evaluation of flap perfusion based on clinical parameters only

Study population: Patients scheduled for elective surgery for autologous breast reconstruction, uni- or bilateral, using DIEP or muscle sparing transverse rectus abdominis muscle (msTRAM) flaps. Female patients 18 years of age and older.

Intervention (if applicable): evaluation of flap perfusion based on 1) clinical parameters, and 2) fluorescence imaging using ICG

Main study parameters/endpoints: Difference in percentage of fat necrosis after autologous breast reconstruction using DIEP flaps between patients in whom fluorescence imaging was used and patients in whom flaps were clinically assessed.

• Study Type: Interventional
• Enrollment (Anticipated): 280
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Alexander L. Vahrmeijer, MD, PhD; Phone Number: +31 71 526 2309; Email: a.l.vahrmeijer@lumc.nl
• Study Contact Backup: Name: Pieter S. Verduijn, MD; Phone Number: 0715296212; Email: P.S.Verduijn@lumc.nl

Study Locations

• Netherlands
  • Leiden, Netherlands, 2333ZA
    • Recruiting
    • Leiden University Medical Center
    • Contact: Alexander L. Vahrmeijer, MD, PhD; Phone Number: +31 71 526 2309; Email: a.l.vahrmeijer@lumc.nl
    • Contact: Pieter S. Verduijn, MD; Phone Number: +31715296212; Email: p.s.verduijn@lumc.nl
    • Sub-Investigator: Floris P Tange, Bsc
  • Rotterdam, Netherlands, 3015GD
    • Recruiting
    • Erasmus Medical Center
    • Contact: Marc A.M. Mureau, MD, PhD; Phone Number: +31 614390753; Email: m.mureau@erasmusmc.nl

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Female patients 18 years of age and older
2. Who underwent a mastectomy for breast cancer or prophylactic due to genetic predisposition
3. Patients scheduled for elective surgery for autologous breast reconstruction, uni- or bilateral, using DIEP or msTRAM flaps. In case of bilateral breast reconstruction the flaps should be bilateral anastomosed.
4. Written informed consent

Exclusion Criteria:

1. Allergy to ICG, iodine or shellfish
2. Any medical condition that in the opinion of the investigators could potentially jeopardize the safety of the patient
3. Impaired renal function defined as eGFR< 50 mL/min/1.73m2 (this can be seen in the standard preoperative lab results)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Interventional study arm; Surgery will be performed according to local protocol. Flap viability during adequate hemodynamic conditions is evaluated a standard of care. Then after anastomosis of the flap but before the inset, the second intervention is performed. Intervention: evaluation of the perfusion of the skin and fat with fluorescence imaging using ICG. The flap is marked according to the fluorescence imaging evaluation, and parts without perfusion are resected. The remaining flap is inset to the remaining breast skin.	Diagnostic test: Near-infrared fluorescence imaging of perfusion; Imaging with ICG near-infrared fluorescence is performed besides clinical judgement of the DIEP flap for perfusion evaluation. Based on fluorescence imaging, additional malperfused area(s) are resected.
No Intervention: Control arm; Surgery will be performed according to local protocol.Flap viability during adequate hemodynamic conditions is evaluated as standard of care. Then after anastomosis of the flap but before the inset, the surgeon will leave the room, the researcher will make a recording of the flap and this will have no consequences for the procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical relevant fat necrosis	Clinically relevant fat necrosis is defined as a palpable mass, either painful or not, and with or without aesthetic complaints, and developed within three months after surgery. The following grading system according to Lie et al. is used. Only grade III till IV is classified as clinical relevant fat necrosis. III: Major compromised reconstructive outcome, flap involvement:15-50%, clinical findings: Major contour defects (multiple), surgical management: Debridement/secondary procedure IV: Subtotal poor reconstructive outcome, flap involvement: >50%, clinical findings: Skin defects, inadequate volume, volume loss, surgical management: Second local flap/ re-intervention initial flap	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantify perfusion of flaps	Based on NIRF recordings and correlate these to the development of fat necrosis.	3 months
Registration of re-interventions	necessary to treat fat necrosis, in numbers and percentages	3 months
Registration of postoperative complications	in numbers and percentages	3 months
Duration of surgery in minutes	Of all surgical procedures included	1 day
Percentage extra resected tissue	of initial flap in grams based on perfusion assessment	1 day
Personal experience/opinion of surgeon performing surgery with fluorescent imaging using ICG.	After every surgery the NASA TASK Load Index is taken by the surgeon.	1 day
Patient satisfaction	using BREAST-Q questionnaire, this is an validated questionnaire that is used in multiple research for measuring patient satisfaction	3 months

Collaborators and Investigators

• Sponsor: Leiden University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Anticipated): September 1, 2025
• Study Completion (Anticipated): October 1, 2025

Study Registration Dates

• First Submitted: August 17, 2022
• First Submitted That Met QC Criteria: August 17, 2022
• First Posted (Actual): August 19, 2022

Study Record Updates

• Last Update Posted (Actual): August 19, 2022
• Last Update Submitted That Met QC Criteria: August 17, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Breast reconstruction; Indocyanine green; Perfusion; Fat necrosis; Near-infrared fluorescence imaging; Free flap surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Fat Necrosis
• Other Study ID Numbers: NL 68623.058.18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No