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

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ClinicalTrials.gov Identifier: NCT03769597
Recruitment Status : Recruiting
First Posted : December 7, 2018
Last Update Posted : January 23, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital, Limoges

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.


Condition or disease Intervention/treatment Phase
Cirrhosis Renal Drug: Iohexol Inj 300 MG/ML Phase 4

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).


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 9 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Description of the Evolution of Plasma and Urinary Concentrations of Iohexol in a Cirrhotic Patient Population: "Pilot Study on 9 Patients"
Actual Study Start Date : January 2, 2019
Estimated Primary Completion Date : January 9, 2020
Estimated Study Completion Date : January 9, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Iohexol

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




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03769597


Contacts
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Contact: PAUL CARRIER, PH + 335 55 05 66 84 pcarrier@hotmail.fr

Locations
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France
University Hospital Recruiting
Limoges, France, 87042
Contact: CARRIER Paul, PH         
Sponsors and Collaborators
University Hospital, Limoges

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Responsible Party: University Hospital, Limoges
ClinicalTrials.gov Identifier: NCT03769597     History of Changes
Other Study ID Numbers: 87RI18_0007 (DFG HEP)
First Posted: December 7, 2018    Key Record Dates
Last Update Posted: January 23, 2019
Last Verified: September 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Limoges:
Cirrhosis Renal
GFR
renal function
Bayesian model
plasma clearance
iohexol

Additional relevant MeSH terms:
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Fibrosis
Pathologic Processes