search
Back to results

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

Primary Purpose

Cirrhosis Renal

Status
Completed
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
Iohexol Inj 300 MG/ML
Sponsored by
University Hospital, Limoges
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cirrhosis Renal focused on measuring Cirrhosis Renal, GFR, renal function, Bayesian model, plasma clearance, iohexol

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Iohexol administration

Arm Description

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

Outcomes

Primary Outcome Measures

Change of plasma concentrations of iohexol in a population of 9 cirrhotic patients from rich kinetics.
Plasma concentration curves for iohexol according to the time.
Change of urinary concentrations of iohexol in a population of 9 cirrhotic patients from rich kinetics.
Urine concentration curves for iohexol according to the time.

Secondary Outcome Measures

Calculate the renal clearance of iohexol.
Renal clearance of iohexol obtained by noncompartmental analysis.
Calculate the plasma clearance of iohexol.
Urinary clearance of iohexol obtained by noncompartmental analysis.
Develop a pharmacokinetic model for the estimation of renal clearance from plasma clearance.
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.
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)
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.
Determine in the model of plasmatic clearance the relevant covariates.
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.

Full Information

First Posted
November 30, 2018
Last Updated
September 24, 2019
Sponsor
University Hospital, Limoges
search

1. Study Identification

Unique Protocol Identification Number
NCT03769597
Brief Title
Description of the Evolution of Plasma and Urinary Concentrations of Iohexol in a Cirrhotic Patient Population
Acronym
DFG HEP
Official Title
Description of the Evolution of Plasma and Urinary Concentrations of Iohexol in a Cirrhotic Patient Population: "Pilot Study on 9 Patients"
Study Type
Interventional

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
January 2, 2019 (Actual)
Primary Completion Date
August 28, 2019 (Actual)
Study Completion Date
August 28, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Limoges

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cirrhosis Renal
Keywords
Cirrhosis Renal, GFR, renal function, Bayesian model, plasma clearance, iohexol

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Iohexol administration
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Iohexol Inj 300 MG/ML
Intervention Description
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
Primary Outcome Measure Information:
Title
Change of plasma concentrations of iohexol in a population of 9 cirrhotic patients from rich kinetics.
Description
Plasma concentration curves for iohexol according to the time.
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
Title
Change of urinary concentrations of iohexol in a population of 9 cirrhotic patients from rich kinetics.
Description
Urine concentration curves for iohexol according to the time.
Time Frame
0 minute, 4 hours, 8 hours, 12 hours, 24 hours
Secondary Outcome Measure Information:
Title
Calculate the renal clearance of iohexol.
Description
Renal clearance of iohexol obtained by noncompartmental analysis.
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
Title
Calculate the plasma clearance of iohexol.
Description
Urinary clearance of iohexol obtained by noncompartmental analysis.
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
Title
Develop a pharmacokinetic model for the estimation of renal clearance from plasma clearance.
Description
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.
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
Title
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)
Description
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.
Time Frame
0 minute, 24 hours
Title
Determine in the model of plasmatic clearance the relevant covariates.
Description
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.
Time Frame
0 minute, 24 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
University Hospital
City
Limoges
ZIP/Postal Code
87042
Country
France

12. IPD Sharing Statement

Learn more about this trial

Description of the Evolution of Plasma and Urinary Concentrations of Iohexol in a Cirrhotic Patient Population

We'll reach out to this number within 24 hrs