Description of the Evolution of Plasma and Urinary Concentrations of Iohexol in a Cirrhotic Patient Population (DFG HEP)

September 24, 2019 updated by: University Hospital, Limoges

Description of the Evolution of Plasma and Urinary Concentrations of Iohexol in a Cirrhotic Patient Population: "Pilot Study on 9 Patients"

Background: It is important to accurately assess the glomerular filtration rate (GFR) of patients with liver diseases, particularly cirrhosis, to deliver care and adjust the drugs' posology.

Purpose: The frequency of chronic renal failure is underestimated in patients with advanced liver disease and the difficulty to assess kidney failure justifies the investigator's study, which aims to describe, by means of a population pharmacokinetic model, the evolution of plasma and urinary concentrations of iohexol, an effective non-ionic, water-soluble contrast agent which is used in radiographic procedures, in cirrhotic patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Cirrhosis is often complicated by kidney failure and the prognostic value of renal function (serum creatinine) during cirrhosis is included in the MELD model. In addition, chronic kidney disease (15%) after liver transplantation is also an independent mortality factor.

The most commonly used methods to estimate GFR are based on creatinine, but in patients suffering from advanced hepatic disease, such as cirrhosis, this parameter is incorrect, due to the low creatinine production and potentially to elevated serum bilirubin and decreased albumin levels. Furthermore, ascites can interfere with serum creatinine concentration. In this condition, all creatinine-based evaluations of GFR overestimate gold standard-measured GFR. Specific eGFR equations for liver disease or new approaches for estimating GFR may be necessary.

The plasma clearance of iohexol is a recognized technique for the measurement of the glomerular filtration rate (GFR).

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Limoges, France, 87042
        • University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with advanced liver disease, with potential indication for liver transplantation, with or without ascites :

    • No ascites: 3 patients.
    • Grade 1 (mild): ascites only detectable by ultrasound examination. 3 patients.
    • Grade 2 (moderate) and Grade 3 (wide): clinically significant ascites, causing moderate symmetrical distension of the abdomen, or causing severe abdominal distension. 3 patients.
  • Patients will be over 18 years, affiliated to a social security scheme and give their informed consent.

Exclusion Criteria:

  • Hypersensitivity to the active substance to the products of iodinated contrasts or to any of the excipients mentioned in Composition section
  • History of major or cutaneous immediate reaction delayed injection of iodinated contrast medium (Omnipaque)
  • Patients with thyrotoxicosis
  • Asthmatic patients
  • Patient with a history of dysthyroidism
  • Patients with severe cardiovascular disease
  • Patients with central nervous system disorders especially vascular
  • Patients with pheochromocytoma
  • Patients with myasthenia
  • Patients with sickle cell disease
  • Patients with autoimmune disease
  • Patients treated with metformin
  • Patients requiring anesthesia on the first day of levies
  • Patients with an injection of iodine contrast during hospitalization and in both previous weeks. Gadolinium injections are not not contraindicated
  • Patients under guardianship or curatorship or incapacitated give informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Iohexol administration
After injecting a loading dose of 5ml of Iohexol Inj 300 MG/ML bolus, blood samples will be taken at given times for 24 hours. The urinary samples will be taken at each urination, with measurement of the exact volume and times
Drug: Iohexol Inj 300 MG/ML
After injecting a loading dose of 5ml of iohexol bolus, blood samples will be taken at given times for 24 hours. The urinary samples will be taken at each urination, with measurement of the exact volume and times

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of plasma concentrations of iohexol in a population of 9 cirrhotic patients from rich kinetics.
Time Frame: 0 minute, 15 minute, 30 minute, 1 hour, 90 minute, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours
Plasma concentration curves for iohexol according to the time.
0 minute, 15 minute, 30 minute, 1 hour, 90 minute, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours
Change of urinary concentrations of iohexol in a population of 9 cirrhotic patients from rich kinetics.
Time Frame: 0 minute, 4 hours, 8 hours, 12 hours, 24 hours
Urine concentration curves for iohexol according to the time.
0 minute, 4 hours, 8 hours, 12 hours, 24 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Calculate the renal clearance of iohexol.
Time Frame: 0 minute, 15 minute, 30 minute, 1 hour, 90 minute, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours
Renal clearance of iohexol obtained by noncompartmental analysis.
0 minute, 15 minute, 30 minute, 1 hour, 90 minute, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours
Calculate the plasma clearance of iohexol.
Time Frame: 0 minute, 15 minutes, 30 minutes, 1 hour, 90 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours
Urinary clearance of iohexol obtained by noncompartmental analysis.
0 minute, 15 minutes, 30 minutes, 1 hour, 90 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours
Develop a pharmacokinetic model for the estimation of renal clearance from plasma clearance.
Time Frame: 0 minute, 15 minutes, 30 minutes, 1 hour, 90 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hrs
The evaluation of the performance of the model will be based on its ability to predict iohexol concentrations, expressed through (%) and accuracy (root of mean bias squared = RMSE) between urinary concentrations and predicted plasma levels and urinary concentrations and observed plasma levels.
0 minute, 15 minutes, 30 minutes, 1 hour, 90 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hrs
Evaluate the correlation between plasma clearance of iohexol obtained by the model and The GFR estimated by (CKD-EPI formula B, MDRD4 and MDRD6 formulas C, renal clearance of cystatine C)
Time Frame: 0 minute, 24 hours
Linear Correlation Coefficients and Point Clouds between the plasma clearance of iohexol estimated by model and the DFGs calculated by the different methods. Bland Altman curves will also be drawn.
0 minute, 24 hours
Determine in the model of plasmatic clearance the relevant covariates.
Time Frame: 0 minute, 24 hours
Evaluation of covariates by multiple linear regression and point clouds (continuous covariates) or Mann Whitney and box plots (categorical covariates). Inclusion of covariates characterized by a P <0.01 in the model. Looking for covariates that will influence the relationship between plasma clearance and renal clearance : grade of intensity of ascites. 2 grades: minimal, (ultrasound) or moderate and bulky, age, weight (of the day and H24), sex, diuresis of 24 hours, albumin, natriuresis, taking diuretics (nature and dose), other drugs that can influence GFR, biological stigmata of hepatic insufficiency or portal hypertension: bilirubin, albumin, INR, phosphatases, Child Pugh score, MELD score.
0 minute, 24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Limoges

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

January 2, 2019

Primary Completion (ACTUAL)

August 28, 2019

Study Completion (ACTUAL)

August 28, 2019

Study Registration Dates

First Submitted

November 30, 2018

First Submitted That Met QC Criteria

December 6, 2018

First Posted (ACTUAL)

December 7, 2018

Study Record Updates

Last Update Posted (ACTUAL)

September 25, 2019

Last Update Submitted That Met QC Criteria

September 24, 2019

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 87RI18_0007 (DFG HEP)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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