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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Acute Kidney Injury, Renal Insufficiency

Intervention / Treatment
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* Drug: Hydration strategy using saline
* Drug: Hydration strategy using sodium bicarbonate
* Drug: L-carnitine
* Procedure: Coronarography


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bicarbonate<br>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<br>* 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.<br>Procedure: Coronarography<br>* 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.<br>|
| Active Comparator: Saline<br>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 | Drug: Hydration strategy using saline<br>* 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.<br>* Other names: Sodium chloride hydration;Procedure: Coronarography<br>* 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.<br>|
| Experimental: Bicar + L-Carnitine<br>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<br>* 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.<br>Drug: L-carnitine<br>* 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.<br>Procedure: Coronarography<br>* 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.<br>|
| Experimental: Saline + L-carnitine<br>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 | Drug: Hydration strategy using saline<br>* 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.<br>* Other names: Sodium chloride hydration;Drug: L-carnitine<br>* 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.<br>Procedure: Coronarography<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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contrast induced nephropathy, hydration strategy, L-carnitine