Preventing Contrast-induced Nephropathy: Evaluating Hydration Strategies and L-carnitine Administration (CinBiCarn)

Preventing Nephropathy Induced by Iodinated Contrast Media in Patients With Renal Impairment: a Randomized Trial Evaluating the Effectiveness of Two Hydration Strategies and L-carnitine Administration

The general objective of this open, pilot study is to characterize biological parameters related to acute kidney injury among patients undergoing a programmed coronarography with injection of contrast material. The study focuses on two main factors that may influence acute kidney injury: (1) sodium chloride hydration strategy versus sodium bicarbonate hydration strategy and (2) presence of oral L-carnitine treatment versus absence of oral L-carnitine treatment. We will also test for a potential interaction between these two factors.

Study Overview

• Status: Terminated
• Conditions: Renal Insufficiency; Acute Kidney Injury
• Intervention / Treatment: Drug: Hydration strategy using sodium bicarbonate; Procedure: Coronarography; Drug: Hydration strategy using saline; Drug: L-carnitine

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Angers, France, 49933
    • CHU d'Angers - Hôtel-Dieu
  • Avignon, France, 84902
    • CH d'Avignon - Centre Hospitalier Henri Duffaut
  • Montpellier, France, 34295
    • CHU de Montpellier - Hôpital Lapeyronie
  • Perpignan, France, 66046
    • CH de Perpignan - Hôpital Saint Jean
  • Gard
    • Nîmes Cedex 09, Gard, France, 30029
      • CHU de Nimes - Hopital Universitaire Caremeau

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• The patient must have given his/her informed and signed consent
• The patient must be insured or beneficiary of a health insurance plan
• The patient is scheduled for a coronarography
• The patient can come back to the hospital on days 2 and 7 after the coronarography for follow up
• The patient has moderate to severe renal insufficiency (glomerular filtration rate < 60 ml / min / 1.73 m^2)
• The patient has not had any oral antidiabetic treatments, or diuretic treatments, within 48 hours preceding the coronarography
• Lack of treatment with ACE inhibitors or ARA2 24 hours prior to coronary

Exclusion Criteria:

• The patient is participating in another study
• The patient is in an exclusion period determined by another study
• The patient is under judicial protection
• The patient is under any kind of guardianship
• The patient refuses to sign the consent form
• It is impossible to correctly inform the patient
• The patient is unable to participate in follow-up visits at days 2 and 7 after the coronarography
• The patient is pregnant or breastfeeding
• The patient is taking L-carnitine
• The patient has a contra indication for a treatment used in this study
• Acute heart failure
• Infarction, acute phase
• Hemodialysis patient
• Myeloma
• Epileptic patient treated with Depakine (valproic acid) (carnitine can lower epilepsy-related thresholds by speeding up the metabolism of Depakine)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bicarbonate; The patients included in this arm will be administered a hydration regime for the prevention of contrast-induced nephropathy containing sodium bicarbonate. Intervention: Hydration strategy using sodium bicarbonate Intervention: Coronarography	Drug: Hydration strategy using sodium bicarbonate; For 4-6 hours before the coronarography and for 4-6 hours after the coronarography, 500 ml of isotonic sodium bicarbonate solution (1.4%) will be administered via a slow intravenous solution.; Procedure: Coronarography; All patients included in this study are programmed for a coronarography with injection of contrast material (either iodixanol or ioxaglate). The day of coronarography = Day 0.
Active Comparator: Saline; The patients included in this arm will be administered a hydration regime for the prevention of contrast-induced nephropathy using sodium chloride solution. Intervention: Hydration strategy using saline Intervention: Coronarography	Procedure: Coronarography; All patients included in this study are programmed for a coronarography with injection of contrast material (either iodixanol or ioxaglate). The day of coronarography = Day 0.; Drug: Hydration strategy using saline; For 12 hours preceding the coronarography, and for 12 following the coronarography, 0.9% sodium chloride at 1 ml/kg/h is administered via a slow intravenous perfusion.; Other Names: Sodium chloride hydration
Experimental: Bicar + L-Carnitine; The patients included in this arm will be administered a hydration regime for the prevention of contrast-induced nephropathy containing sodium bicarbonate. They will also receive an oral L-carnitine solution on days -1, 0, 1 to 7. Intervention: Hydration strategy using sodium bicarbonate Intervention: L-carnitine Intervention: Coronarography	Drug: Hydration strategy using sodium bicarbonate; For 4-6 hours before the coronarography and for 4-6 hours after the coronarography, 500 ml of isotonic sodium bicarbonate solution (1.4%) will be administered via a slow intravenous solution.; Procedure: Coronarography; All patients included in this study are programmed for a coronarography with injection of contrast material (either iodixanol or ioxaglate). The day of coronarography = Day 0.; Drug: L-carnitine; Before the coronarography (D-1), 1 gram of L-carnitine is administered via an oral solution that can be diluted in a small amount of sugar water if necessary. This administration corresponds to the beginning of a hydration protocol. For days 0 to 7 after the coronarography, patients are administered an oral L-carnitine solution (3 grams of L-carnitine per day). The latter may be diluted in a small amount of sugar water if needed.
Experimental: Saline + L-carnitine; The patients included in this arm will be administered a hydration regime for the prevention of contrast-induced nephropathy using sodium chloride solution. They will also receive an oral L-carnitine solution on days -1, 0, 1 to 7. Intervention: Hydration strategy using saline Intervention: L-carnitine Intervention: Coronarography	Procedure: Coronarography; All patients included in this study are programmed for a coronarography with injection of contrast material (either iodixanol or ioxaglate). The day of coronarography = Day 0.; Drug: Hydration strategy using saline; For 12 hours preceding the coronarography, and for 12 following the coronarography, 0.9% sodium chloride at 1 ml/kg/h is administered via a slow intravenous perfusion.; Other Names: Sodium chloride hydration; Drug: L-carnitine; Before the coronarography (D-1), 1 gram of L-carnitine is administered via an oral solution that can be diluted in a small amount of sugar water if necessary. This administration corresponds to the beginning of a hydration protocol. For days 0 to 7 after the coronarography, patients are administered an oral L-carnitine solution (3 grams of L-carnitine per day). The latter may be diluted in a small amount of sugar water if needed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in glomerular filtration rate	The change in MDRD glomerular filtration rate before coronarography, and 48 hours after the injection of contrast material.	baseline versus 48 hours after contrast injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Contrast induced nephropathy?	The presence/absence of contrast induced nephropathy, defined by the presence of at least one of the following: a >= 25% increase in creatinemia as compared to baseline; an absolute increase >= 44 µmol/L in creatinemia as compared to baseline; a decrease >= 25% in glomerular filtration rate as compared to baseline	Day 2
Contrast induced nephropathy?	The presence/absence of contrast induced nephropathy, defined by the presence of at least one of the following: a >= 25% increase in creatinemia as compared to baseline; an absolute increase >= 44 µmol/L in creatinemia as compared to baseline; a decrease >= 25% in glomerular filtration rate as compared to baseline	Day 3
Contrast induced nephropathy?	The presence/absence of contrast induced nephropathy, defined by the presence of at least one of the following: a >= 25% increase in creatinemia as compared to baseline; an absolute increase >= 44 µmol/L in creatinemia as compared to baseline; a decrease >= 25% in glomerular filtration rate as compared to baseline	Day 7
Change in creatinemia	The brute change in creatinemia between baseline and Day 2	baseline versus Day 2
Change in creatinemia	The brute change in creatinemia between baseline and Day 3	baseline versus Day 3
Change in creatinemia	The brute change in creatinemia between baseline and Day 7	baseline versus Day 7
% Change in creatinemia	% change in creatinemia between baseline and Day 2	baseline versus Day 2
% Change in creatinemia	% change in creatinemia between baseline and Day 3	baseline versus Day 3
% Change in creatinemia	% change in creatinemia between baseline and Day 7	baseline versus Day 7
Change in glomerular filtration rate compared to baseline	Change in glomerular filtration (MDRD; ml/min/1.73m^2) rate compared to baseline	baseline versus Day 2
Change in glomerular filtration rate compared to baseline	Change in glomerular filtration (MDRD; ml/min/1.73m^2) rate compared to baseline	baseline versus Day 3
Change in glomerular filtration rate compared to baseline	Change in glomerular filtration (MDRD; ml/min/1.73m^2) rate compared to baseline	baseline versus Day 7
Quantity of contrast material injected / glomerular filtration rate		Day 0 - just after coronarography
Quantity of iodine injected / glomerular filtration rate		Day 0, just after coronarography
Hemodialysis necessary?	Was hemodialysis required for the patient? yes/no	Day 7
Mortality	The patient passed away during the study. yes/no	Day 7
Change in serum ngal	The change in serum ngal (neutrophil gelatinase associated lipocalin) between baseline and 4 hours after the injection of contrast material.	baseline (just before coronarography) versus 4 hours after contrast injection

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Investigators: Principal Investigator: Pascal Reboul, MD, Centre Hospitalier Universitaire de Nîmes

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: February 6, 2013
• First Submitted That Met QC Criteria: February 7, 2013
• First Posted (Estimate): February 8, 2013

Study Record Updates

• Last Update Posted (Estimate): March 22, 2016
• Last Update Submitted That Met QC Criteria: March 21, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: L-carnitine; contrast induced nephropathy; hydration strategy
• Additional Relevant MeSH Terms: Urologic Diseases; Kidney Diseases; Renal Insufficiency; Acute Kidney Injury
• Other Study ID Numbers: LOCAL/2012/PR-03; 2012-004134-42 (EudraCT Number)