Cardiox Liver Function Test Pivotal Trial (LFT-0002)

A Pivotal, Within Subject, Comparison of the LFT™ Dye Monitor System to the Indocyanine Green Dye (ICG) Serial Blood Plasma Disappearance Rate in Patients With Impaired and Non-Impaired Hepatic Function

Performance evaluation of LFT Dye Monitor System using ICG - plasma disappearance rate value (PDR) to assess liver function in normal patients as well as in patients with mild to severe hepatic impairment compared to manual Serum ICG PDR.

Study Overview

• Status: Withdrawn
• Conditions: Liver Failure; Hepatic Failure
• Intervention / Treatment: Drug: 0.1 mg/kg ICG Dose; Drug: 0.5 mg/kg ICG dose

Detailed Description

Indocyanine green (ICG) is a water-soluble, non-toxic tricarbocyanine dye, extracted principally by hepatic parenchymal cells and excreted almost entirely into the bile without enterohepatic circulation. Clinically, its elimination rate is used primarily to measure hepatic function and liver blood flow. ICG studies are also used in ophthalmic angiography and the determination of cardiac output.

Beginning about 1959, the first human clinical studies were reported wherein an indocyanine green (ICG) bolus was injected into a vein, and then blood samples were withdrawn over a period of time and analyzed for ICG concentrations. This method is referred to hereinafter as the serial blood sampling method. These blood samples are sent to a clinical laboratory for a multi-step process of centrifuging, separation and spectrophotometric measurements of ICG levels. The laboratory-based measured levels of residual ICG levels are then used to determine the ICG clearance rate and R15 value or residual amount of dye remaining after 15 minutes, expressed as a percentage of the initial concentration.

As an alternative to the time- and labor-consuming serial blood sampling method, a non-invasive technique was first reported nearly 20 years ago. In the first published clinical study, Ishigami reported the use of a pulse dye densitometry (PDD) method to transcutaneously detect the rate of clearance of ICG from the bloodstream to be referred to hereinafter as dynamic liver function testing.

PDD expresses ICG elimination in terms of the indocyanine green plasma disappearance rate because only relative ICG concentration changes are assessed. The results of this noninvasive method have been shown to correlate with those obtained by the invasive method used in critically ill patients (hemodynamically unstable and stable), and in patients after liver surgery.

ICG elimination rate after liver transplantation measured by either invasive or noninvasive ICG methods is widely used to evaluate graft function. Studies have shown that ICG elimination, measured on the day of transplantation, reflects graft function and can be used to predict graft viability and the expected survival of the patient. Sequential measurements of ICG elimination between days 0 and 28 of transplantation, have been shown to predict clinical outcome in the early postoperative period after living donor transplantation. All of the studies have shown that the ICG elimination rate is an accurate test for evaluating liver dysfunction, but lacks the ability to differentiate the underlying causes of the hepatic dysfunction.

Unlike all currently existing PDD methods for performing liver function testing, LFT Dye Monitor System employs a more sensitive method for the transcutaneous measurement of ICG concentration level in the blood using NIR fluorescence, with a sensor that is attached loosely to the scaphoid fossa of the ear. Thus, the chemical properties of ICG dye to fluoresce when properly excited are used in the LFT system to enable much lower concentrations of ICG to be detectable.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female between 18 to 75 years of age inclusive, at the time of Screening.
2. Voluntarily provide written informed consent.

3. Female patients are eligible only if all of the following apply:

   • Not pregnant (negative urine pregnancy test at the Screening visit);
   • Not lactating;
   • Not planning to become pregnant within the duration of the study;
   • Surgically sterile, or at least 2 years postmenopausal, or is practicing an acceptable form of birth control (defined as the use of an intrauterine device, a barrier method with spermicide, condoms, subdermal implant, oral contraceptives, abstinence, or sterilization of monogamous partner) for greater than 60 days prior to Screening and commits to the use of the acceptable form of birth control for the duration of the study.
4. If a healthy volunteer; is considered to be in generally good health, in the opinion of the Investigator, at the Screening visit based upon the results of their medical and surgical history, vital signs, physical examination, and clinical laboratory tests.
5. Prior to receiving any ICG injections the subject agrees to be fasting for at least eight (8) hours.
6. If a subject with liver cirrhosis; is considered to be in general satisfactory health, in the opinion of the Investigator (other than their hepatic impairment) at the Screening visit based upon the results of their medical and surgical history, vital signs, physical examination, and non-hepatic clinical laboratory tests.
7. Liver cirrhosis subjects must have a clinical diagnosis of hepatic impairment based on documented evidence of hepatic cirrhosis by medical history, or previous liver biopsy, or hepatic ultrasound; which conforms to the criteria for class A or B or C of the Childs-Pugh classification (Appendix B); and are expected to require an ICG liver function study, such as for liver transplantation, liver resection, liver cirrhosis prognosis evaluation, functional liver cell mass and/or general liver dysfunction evaluations.
8. On stable drug therapy that is not expected to change (i.e. in dose, frequency, additions or deletions of agents) for at least 2 weeks before ICG dye injection.
9. Must, in the Investigator's opinion, be able to comply with study procedures.
10. If the Subject is being enrolled in the fifth group they have a diagnosis of acute liver failure (ALF) as defined by the Principal Investigator.

Exclusion Criteria:

1. Have any clinically significant condition or unstable current illness that would, in the opinion of the Investigator, preclude study participation or interfere with the assessment of the procedure;
2. Known allergy or sensitivity to ICG dye or history of allergy to iodides;
3. Actively bleeding associated with acute blood volume changes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LFT Dye Detection Monitor	Drug: 0.1 mg/kg ICG Dose; least efficacious dose; Other Names: LFT Dose; Drug: 0.5 mg/kg ICG dose; per package insert
Active Comparator: Serial Blood Draws	Drug: 0.5 mg/kg ICG dose; per package insert

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
plasma disappearance rate	Study Day 1

Secondary Outcome Measures

Outcome Measure	Time Frame
physical examinations	Study Day 1
vital signs	Study Day 1
adverse events	Study Day 1

Collaborators and Investigators

• Sponsor: Cardiox Corporation
• Investigators: Study Director: Michael Jopling, MD, Medical Director, Cardiox Corporation

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Anticipated): May 1, 2016
• Study Completion (Anticipated): May 1, 2016

Study Registration Dates

• First Submitted: September 15, 2015
• First Submitted That Met QC Criteria: September 16, 2015
• First Posted (Estimate): September 17, 2015

Study Record Updates

• Last Update Posted (Estimate): January 15, 2016
• Last Update Submitted That Met QC Criteria: January 14, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: albumin; NASH; cirrhosis; liver; hepatitis C; prothrombin time; liver transplant; fluorescence; hepatic; liver disease; ALT; AHF; LFT; PDR; MELD; indocyanine green dye; hepatic assessment; ICG dye; Diagnostic Green; Pulsion; Akorn; Cardiox; anazen; essence; dye detection monitor; Earpads; flow sensor; scaphoid fossa; acute hepatic failure; pulse dye densitometry; near infra-red; serial blood draws; plasma disappearance rate; R15; k coefficient; transcutaneously; liver donor; liver dysfunction; Child-Pugh; AST; GGT; alk phos; serum ICG; liver function tests
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency
• Other Study ID Numbers: LFT-0002