Clinical trial NCT03769597: Description of the Evolution of Plasma and Urinary Concentrations of Iohexol in a Cirrhotic Patient Population
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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cirrhosis Renal
Keywords: Cirrhosis Renal
GFR
renal function
Bayesian model
plasma clearance
iohexol
Lead sponsor: University Hospital, Limoges
Sponsor class: OTHER
First posted: 2018-12-07
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Change of plasma concentrations of iohexol in a population of 9 cirrhotic patients from rich kinetics.
timeFrame: 0 minute, 15 minute, 30 minute, 1 hour, 90 minute, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours
measure: Change of urinary concentrations of iohexol in a population of 9 cirrhotic patients from rich kinetics.
timeFrame: 0 minute, 4 hours, 8 hours, 12 hours, 24 hours
Secondary outcomes:
measure: Calculate the renal clearance of iohexol.
timeFrame: 0 minute, 15 minute, 30 minute, 1 hour, 90 minute, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours
measure: Calculate the plasma clearance of iohexol.
timeFrame: 0 minute, 15 minutes, 30 minutes, 1 hour, 90 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours
measure: Develop a pharmacokinetic model for the estimation of renal clearance from plasma clearance.
timeFrame: 0 minute, 15 minutes, 30 minutes, 1 hour, 90 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hrs
measure: 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)
timeFrame: 0 minute, 24 hours
measure: Determine in the model of plasmatic clearance the relevant covariates.
timeFrame: 0 minute, 24 hours
Other outcomes:
Locations:
city: Limoges
country: France
facility: University Hospital
Study officials:
References: