Indocyanine Green for Perfusion Assessment of DIEP Flaps

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Fat Necrosis

Intervention / Treatment
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* Diagnostic Test: Near-infrared fluorescence imaging of perfusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients 18 years of age and older Who underwent a mastectomy for breast cancer or prophylactic due to genetic predisposition 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. Written informed consent Exclusion Criteria: Allergy to ICG, iodine or shellfish Any medical condition that in the opinion of the investigators could potentially jeopardize the safety of the patient Impaired renal function defined as eGFR< 50 mL/min/1.73m2 (this can be seen in the standard preoperative lab results)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Interventional study arm<br>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<br>* 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.<br>|
| No Intervention: Control arm<br>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?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fat necrosis, Near-infrared fluorescence imaging, Indocyanine green, Free flap surgery, Breast reconstruction, Perfusion