Intraoperative ICG for Systemic Sclerosis

A Prospective Study of the Utility of Intraoperative, Quantitative Indocyanine Green Angiography in Microvascular Surgery for Systemic Scerlosis

The primary objective of this study is to evaluate the relative intraoperative improvement in perfusion between arterial reconstruction and sympathectomies with quantitative ICG. A minimum of 40 patients, 20 Sympathectomy Prior to Bypass (group 1) and 20 Bypass Prior to Sympathectomy (group 2), will be recruited for this study. This study will enroll participants in a one to one randomized study design. There is the potential risk of loss of confidentiality. The study involves the intraoperative assessment of perfusion by quantitative ICG. ICG is FDA approved for this usage and will be used according to its labeling. Assessment involves intraoperative quantitative ICG data, questionnaires, and patient and physician assessments. There are no additional physical risks associated with participating in this study over and above that of the planned arterial reconstruction (bypass) and sympathectomies.The information collected will be kept confidential and will comply with the HIPAA.

Study Overview

• Status: Withdrawn
• Conditions: Systemic Sclerosis
• Intervention / Treatment: Procedure: Order of two elements of surgical procedure; Drug: Indocyanine Green

Detailed Description

A minimum of 40 patients, 20 Sympathectomy Prior to Bypass (group 1) and 20 Bypass Prior to Sympathectomy (group 2), will be recruited for this study. This study will enroll participants in a 1:1 randomized study design. Participants will serve as their own controls. A consecutive series of patients will be randomized to either Group 1 or 2. Randomization will occur through 40 sealed, opaque sequentially numbered envelopes containing the randomization. Those that qualify and sign consent will be randomized 24hrs prior to surgery. The randomization envelopes will be stored in a locked filing cabinet within the clinical research coordinators office. The subject will know what treatment arm they are in prior to surgery.

Patients will be randomized to Group 1 or 2. If patients are randomized to Group 1, patients will receive sympathectomy prior to bypass during the surgical procedure (see below). If patients are randomized to Group 2, they will received bypass prior to sympathectomy during the surgical procedure (see below). Patients in both groups will be in the study for the next 12 months. Normal clinical practice will not change. Patients in both groups will be examined before surgery. If they provide consent to participate, demographical data, comorbidities, the number and severity of digital ulcerations, and baseline outcome measures for the Michigan Hand Outcome Questionnaire, Disabilities of the Arm, Shoulder and Hand and the Visual Analogue Scale for Pain will be collected.

Patients in both groups will return to the office for routine follow-up at 2 weeks for wound care. The next study visit will occur at 6 weeks. At that time, outcome measures will be again administered and data collected. In accordance with standard clinical practice, the patients will return to the office for examination again at 6 months and 1 year. At these times, the primary clinical outcomes will be collected as well as the patient reported outcomes.

These are normal visits, not outside the scope of routine clinical practice. Intraoperative ICG is also within the scope of routine clinical practice. The dose of ICG and the number of times that it is administered to subjects is the same as in standard of care.

ICG is administered by means of peripheral or central intravenous access, is excreted exclusively by the liver into the bile, and is not associated with risk for nephrotoxicity. The laser diode array utilized by the SPY System emits a near-infrared wavelength that does not require the use of protective eyewear or other safety equipment. The investigators will be using a concentration of 2.5mg/cc. 12.5mg will be administered at each injection of ICG. Complete washout of the ICG occurs after 15 minutes, plenty of time considering the interval surgery that must occur. As per the protocol, ICG will be administered 3 times during the surgery. The patients will receive a total of 37.5mg of ICG, well below the recommended threshold of 2mg/kg. Of note, No significant toxic effects have been observed in humans with the high dose of 5 mg/kg of body weight.

• Study Type: Interventional
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• o Patient has signed an IRB approved, study specific Informed Patient Consent Form.

  • Patient is a male or non-pregnant female age 18 - 85 years at time of study enrollment.
  • Patient has a diagnosis of a systemic sclerosis with vascular obstruction of the hand resulting in digital ischemia, ulceration, and/or gangrene and have failed nonoperative treatments.
  • Patient is willing and able to comply with postoperative scheduled clinical evaluations.

Exclusion Criteria:

• • Patient is undergoing revision surgery.

  • Patient has a diagnosis of avascular necrosis or inflammatory arthritis.

• If, during surgery, the arterial reconstruction could not be performed because the vessel was damaged to the point where there was no appropriate site for a bypass anastomosis.

  • Patient is a prisoner
  • Pregnant women confirmed by testing prior to surgery, and nursing mothers
  • Patient has an allergy to iodine confirmed during initial history and on day of surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Group 1; Order of two elements of surgical procedure: patients in group 1 will receive sympathectomy prior to bypass during the surgical procedure. Indocyanine Green (ICG) will be used in both groups.	Procedure: Order of two elements of surgical procedure; Please see the arm/group descriptions for the order of elements of the surgical procedure in group 1 and group 2.; Drug: Indocyanine Green; Intraoperative ICG has been validated to correlate to postoperative outcomes. ICG is administered by means of peripheral or central intravenous access, is excreted exclusively by the liver into the bile, and is not associated with risk for nephrotoxicity. We will be using a concentration of 2.5mg/cc. 12.5mg will be administered at each injection of ICG. Complete washout of the ICG occurs after 15 minutes, plenty of time considering the interval surgery that must occur. As per the protocol, ICG will be administered 3 times during the surgery. The patients will receive a total of 37.5mg of ICG, well below the recommended threshold of 2mg/kg. No significant toxic effects have been observed in humans with the high dose of 5 mg/kg of body weight.; Other Names: ICG
Other: Group 2; Order of two elements of surgical procedure: Patients in group 2 will receive bypass prior to sympathectomy during the surgical procedure. Indocyanine Green (ICG) will be used in both groups.	Procedure: Order of two elements of surgical procedure; Please see the arm/group descriptions for the order of elements of the surgical procedure in group 1 and group 2.; Drug: Indocyanine Green; Intraoperative ICG has been validated to correlate to postoperative outcomes. ICG is administered by means of peripheral or central intravenous access, is excreted exclusively by the liver into the bile, and is not associated with risk for nephrotoxicity. We will be using a concentration of 2.5mg/cc. 12.5mg will be administered at each injection of ICG. Complete washout of the ICG occurs after 15 minutes, plenty of time considering the interval surgery that must occur. As per the protocol, ICG will be administered 3 times during the surgery. The patients will receive a total of 37.5mg of ICG, well below the recommended threshold of 2mg/kg. No significant toxic effects have been observed in humans with the high dose of 5 mg/kg of body weight.; Other Names: ICG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in perfusion	To compare the relative intraoperative change in perfusion between arterial reconstruction and sympathectomies with quantitative ICG.	Baseline-One Year Follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraoperative change in hand and digit perfusion	To document the immediate intraoperative quantitative change in hand and digit perfusion in combined arterial reconstruction and sympathectomies in patients with systemic sclerosis using intraoperative quantitative ICG.	Baseline-One Year Follow-up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of clinical and intraoperative quantitative ICG measurements	Correlation of primary clinical measures with results of intraoperative quantitative ICG at 1 year postoperative	Baseline-One Year Follow-up
Change in Michigan Hand Outcome Questionnaire	Change in Michigan Hand Outcome Questionnaire	Baseline-One Year Follow-up
Change in Visual Analogue Scale for Pain (VAS)	Change in Visual Analogue Scale for Pain (VAS); patient reported level of pain which is then measured (distance from 0 in mm)	Baseline-One Year Follow-up
Change in Disability of the Arm, Shoulder, and Hand Questionnaire (DASH)	Change in DASH score; scale of 0-100. 30 questions in total with optional work and optional sports/activities questions (with 4 questions each)	Baseline-One Year Follow-up
Complete healing of all ulcers	Complete healing of all ulcers (yes/no)	1 Year Follow-up
Number of all ulcers	Number of all ulcers	1 Year Follow-up
Need for amputation by the end of one-year follow-up	Need for amputation by the end of one-year follow-up (yes/no)	1-year follow-up

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Suhail Mithani, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2017
• Primary Completion (Actual): January 23, 2018
• Study Completion (Actual): January 23, 2018

Study Registration Dates

• First Submitted: April 24, 2017
• First Submitted That Met QC Criteria: May 15, 2017
• First Posted (Actual): May 16, 2017

Study Record Updates

• Last Update Posted (Actual): June 30, 2020
• Last Update Submitted That Met QC Criteria: June 29, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: indocyanine-green; systemic scerlosis
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Connective Tissue Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse
• Other Study ID Numbers: Pro00078686

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