Ignite Creation Date:
2024-05-05 @ 4:58 PM
Last Modification Date:
2024-10-26 @ 9:26 AM
Study NCT ID:
NCT00353340
Status:
COMPLETED
Last Update Posted:
2010-02-25
First Post:
2006-07-17
Brief Title:
Prevention of Contrast Nephropathy by Sodium Bicarbonate Versus Sodium Chloride and N-acetylcysteine
Sponsor:
Shaare Zedek Medical Center
Organization:
Shaare Zedek Medical Center
Study Overview
Official Title:
Prevention of Contrast Nephropathy by Sodium Bicarbonate Versus Sodium Chloride and N-acetylcysteine in Patients Undergoing Cardiac Catheterization
Status:
COMPLETED
Status Verified Date:
2010-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The objective of this study is to assess the efficacy of sodium bicarbonate compared with sodium chloride and oral N-acetylcysteine NAC pretreatment for prevention of contrast nephropathy in patients with advanced renal disease undergoing cardiac catheterisation
Detailed Description:
PROTOCOL
Prevention of Contrast Nephropathy by Sodium Bicarbonate Versus Sodium Chloride and N-Acetylcysteine
Nephrology and Cardiology Services Shaare Zedek Medical Center Jerusalem
1 Background and rationale
The development of acute renal failure following cardiac catheterization has been recognized since the 1970s The syndrome of acute renal failure following cardiac catheterization is presently felt to be due either to atheroembolic disease or what is now referred to as contrast induced nephropathy Since the clinical course of each is different it is now usually not difficult to diagnose acute contrast induced nephropathy
All protocols to prevent contrast nephropathy include the infusion of sodium chloride with or without oral N-acetylcysteine NAC pretreatment although several recent meta-analyses raise some doubt about the efficacy of
Review of Shaare Zedek Medical Center experience from 2000 thru 2003 demonstrated a significant decrease in the incidence of acute contrast induced nephropathy after cardiac catheterization following the introduction of routine NAC usage This effect was detected in a patients with mild renal insufficiency only creatinine less than 15mgdl Patients with higher plasma creatinines did not appear to benefit from NAC prophylaxis
A recent study demonstrated that preventive hydration with sodium bicarbonate was more effective than sodium chloride in patients undergoing radiographic procedures However in that study there was no subdivision of the patients by severity of their kidney disease and it is not clear if sodium bicarbonate was as effective in patients with more severe kidney disease as in those with milder renal impairment In addition the rate duration and kind of fluids that were used for preventive hydration differed from that currently recommended
Because free radicals are postulated to mediate contrast induced nephropathy and their formation is promoted by an acidic environment alkalinizing renal tubular fluid with bicarbonate may reduce renal injury by reducing free radial formation NAC is also known to be a free radical scavenger but since this compound was relatively ineffective in preventing contrast nephropathy in our patients with moderate to severe renal impairment plasma creatinine 15 mg we postulate that sodium bicarbonate may be more effective in the prevention of contrast nephropathy in these high risk patients
The proposed study is designed to test the efficacy of preventive hydration with sodium bicarbonate versus sodium chloride and oral NAC pretreatment in patients with stable advanced renal insufficiency CKD stage 3 and 4-GFR 15-60mlmin173m2 calculated by MDRD formula undergoing cardiac catheterization
2 Study objectives
The objective of this study is to assess the efficacy of sodium bicarbonate compared with sodium chloride and NACpretreatment for prevention of contrast nephropathy in patients with advanced renal disease
3 Outcome measure
The incidence of contrast induced nephropathy defined as 25 or more increase in serum creatinine within 2 days of contrast administration will be assessed
4 Study design
This is a prospective randomized single center trial Patients due to undergo cardiac catheterization either electively or following acute coronary syndromes will be eligible for inclusion Elective patients will be admitted the day before the procedure After baseline assessment and laboratory tests they will be randomly assigned to one of two groups One group will receive 12 hours infusion of 154 meql 09 sodium chloride at a rate of 1mlkg per hour before cardiac catheterization and NAC 600mg x 2d PO the day before and the day of the procedure
The second group will receive 154meql sodium bicarbonate in 5 dextrose in water mixed by the nursing staff by adding 154 ml of 1000 meql sodium bicarbonate to 846 ml of 5 dextrose in water slightly diluting the dextrose concentration to 423The initial IV bolus will be 3 mlkg for one hour before cardiac catheterization Following this bolus patients will receive the same fluid at a rate of 1 mlkg per hour during the contrast exposure and for 6 hours after the procedure
A basic panel of blood chemistries Na K Cl Ca P BUN creatinine total protein albumin complete blood count pH HCO3 pCO2 and O2 sat will be obtained before the procedure and post-procedure day 1 and 2 and until any increase of serum creatinine is resolved GFR will be calculated by MDRD formula in all patients before cardiac catheterization
5 Patient selection
Patients will be identified as study candidates based on preliminary laboratory tests results They will referred from the clinics of Shaare Zedek Kupot Cholim and the inpatient services of Shaare Zedek Medical Center Eligible patients include individuals aged 18 year or older with GFR 15-60mlmin calculated by MDRD formula who were scheduled to undergo cardiac catheterization During the randomized study consecutive eligible patients scheduled for exposure to the nonionic radiographic contrast agent iopamidol 796 mOsmkg H2O 755 mg of iopamidol per milliliter and 370 mg iodine per milliliter will be considered for enrollment
6 Exclusion criteria
i Serum creatinine levels more than 8mgdl or GFR less than 15mlmin
ii Change in serum creatinine levels of ³05mgdl during the previous 24 hours
iii Preexisting dialysis
iv Multiple myeloma
v Pulmonary edema
vi Uncontrolled hypertension treated systolic blood pressure more than 160 mmHg or diastolic blood pressure more than 100mmHg
vii Emergency catheterization
viii Recent exposure to radiographic contrast within two days of the study
ix Allergy to radiocontrast
x Pregnancy
xi Administration of dopamine mannitol or NAC before the study
7 Blinding
The study will be completely blinded The serum creatinine level will be determined in a fully blinded fashion by laboratory personnel The investigators from the Nephrology service will analyze the laboratory data without knowledge of patient study groups The patients will not know to which group they will be randomized The investigators from the Cardiology service will know the patient study groups but will not analyze the patients laboratory tests results
8 Study Methods
Qualified patients who agree to enter the study will be assigned to 1 of 2 treatment groups based on a computer-generated randomization schedule Patients allocated to the sodium chloride-NAC group will receive 154mEqL of sodium chloride at a rate of 1mlkg per hour for 12 hours before cardiac catheterization and NAC 600mgx2d PO the day before and the day of the procedure Patients allocated to the sodium bicarbonate group will receive 154 mEqL of sodium bicarbonate in dextrose and H2O mixed by the Nursing Service by adding 154 mL of 1000 mEqL sodium bicarbonate to 846 mL of 5 dextrose in H2O slightly diluting the dextrose concentration to 423
After appropriate nursing evaluation and initial measurement of blood pressure and weight the pre-contrast fluid will be administered Patients allocated to the sodium chloride-NACgroup will receive 154 mEqL of sodium chloride at a rate of 1mlkg per hour for 12 hours before cardiac catheterization and NAC 600mgx2d PO the day before and the day of the procedure The initial intravenous bolus in the NaHCO3 group will be 3 mLkg per hour for 1 hour immediately before radiocontrast injection Following this patients will receive the same fluid at a rate of 1 mLkg per hour during the contrast exposure and for 6 hours after the procedure For patients weighing more than 110 kg the initial fluid bolus and drip will be limited to those doses administered to a patient weighing 110 kg Diuretics will be routinely withheld on the day of contrast injection A basic panel of blood chemistries Na K Cl Ca P BUN creatinine total protein albumin complete blood count serum pH HCO3 pCO2 and O2 sat will be obtained before the procedure and post-procedure days 1 and 2 and until any increase of serum creatinine is resolved GFR will be calculated by MDRD formula before the procedure
9 Study End Points and Statistical Analysis
The primary outcome measure is development of contrast-induced nephropathy defined by an increase in serum creatinine of 25 or more within 2 days after cardiac catheterization This definition is identical to that used in a recent large meta-analysis in contrast-induced nephropathy Post-contrast creatinine will be assessed the mornings of days 1 and 2 The highest serum creatinine on post-contrast days 1 or 2 will be used to calculate the change in serum creatinine the primary end point
Before beginning the study we estimated the sample size needed for the primary end point of contrast-induced nephropathy Based on our own and other previous data we assumed the development of contrast-induced renal failure in 15 of the sodium chloride-NAC group and 5 of the sodium bicarbonate group Analysis indicated that a sample size of 281 patients would be required to detect a statistically significant difference with a power of 80 two tailed p 005
Tests for significance will be conducted using the t test for continuous variables and c2 or Fisher exact test for categorical variables All analyses will be conducted using SAS software version 82 SAS Institute Inc Cary NC Data will be expressed as mean SD All tests will be 2-tailed with differences reported as significant if p 005
10 Feasibility of the study
The average number of cardiac catheterizations performed in Shaare Zedek Medical Center is 25-30 procedures per week A recent review of 30 consecutive cardiac catheterization patients showed that 8 would be eligible for enrollment in this protocol Thus it should take about 10-12 months to enroll the required number of patients
11 Safety
The infusion of sodium bicarbonate and sodium chloride is safe In the published sodium bicarbonate study bolus administration of hydration fluids caused a moderate increase in both systolic and diastolic blood pressure mean 11mm Hg in the sodium chloride group and 14 mmHg in the sodium bicarbonate group No patients developed clinical heart failure or respiratory distress Since the patients enrolled in our study should have controlled hypertension patients with blood pressure more than 160100 will be excluded this mild elevation in blood pressure should not be problematic
12 Study significance
Contrast induced nephropathy is a common complication of cardiac catheterizations Prophylactic hydration with sodium chloride and NAC which is currently in use is less effective in patients with advanced renal disease and the observed incidence of acute contrast induced nephropathy is approximately 15 In addition the use of this regimen requires preventive hospitalization and may be especially problematic in patients with chronic kidney disease when they require urgent cardiac catheterization If preventive hydration with sodium bicarbonate is as effective or better than the currently used saline-NAC regimen the pretreatment time for cardiac catheterization could be significantly shortened hence permitting its usage before emergent procedure Since emergent procedures preclude the use of current relatively long pretreatment regimens bicarbonate could reduce the incidence of acute contrast induced nephropathy in this highly vulnerable group
Prevention of Contrast Nephropathy by Sodium Bicarbonate Versus Sodium Chloride and N-Acetylcysteine
Nephrology and Cardiology Services Shaare Zedek Medical Center Jerusalem
1 Background and rationale
The development of acute renal failure following cardiac catheterization has been recognized since the 1970s The syndrome of acute renal failure following cardiac catheterization is presently felt to be due either to atheroembolic disease or what is now referred to as contrast induced nephropathy Since the clinical course of each is different it is now usually not difficult to diagnose acute contrast induced nephropathy
All protocols to prevent contrast nephropathy include the infusion of sodium chloride with or without oral N-acetylcysteine NAC pretreatment although several recent meta-analyses raise some doubt about the efficacy of
Review of Shaare Zedek Medical Center experience from 2000 thru 2003 demonstrated a significant decrease in the incidence of acute contrast induced nephropathy after cardiac catheterization following the introduction of routine NAC usage This effect was detected in a patients with mild renal insufficiency only creatinine less than 15mgdl Patients with higher plasma creatinines did not appear to benefit from NAC prophylaxis
A recent study demonstrated that preventive hydration with sodium bicarbonate was more effective than sodium chloride in patients undergoing radiographic procedures However in that study there was no subdivision of the patients by severity of their kidney disease and it is not clear if sodium bicarbonate was as effective in patients with more severe kidney disease as in those with milder renal impairment In addition the rate duration and kind of fluids that were used for preventive hydration differed from that currently recommended
Because free radicals are postulated to mediate contrast induced nephropathy and their formation is promoted by an acidic environment alkalinizing renal tubular fluid with bicarbonate may reduce renal injury by reducing free radial formation NAC is also known to be a free radical scavenger but since this compound was relatively ineffective in preventing contrast nephropathy in our patients with moderate to severe renal impairment plasma creatinine 15 mg we postulate that sodium bicarbonate may be more effective in the prevention of contrast nephropathy in these high risk patients
The proposed study is designed to test the efficacy of preventive hydration with sodium bicarbonate versus sodium chloride and oral NAC pretreatment in patients with stable advanced renal insufficiency CKD stage 3 and 4-GFR 15-60mlmin173m2 calculated by MDRD formula undergoing cardiac catheterization
2 Study objectives
The objective of this study is to assess the efficacy of sodium bicarbonate compared with sodium chloride and NACpretreatment for prevention of contrast nephropathy in patients with advanced renal disease
3 Outcome measure
The incidence of contrast induced nephropathy defined as 25 or more increase in serum creatinine within 2 days of contrast administration will be assessed
4 Study design
This is a prospective randomized single center trial Patients due to undergo cardiac catheterization either electively or following acute coronary syndromes will be eligible for inclusion Elective patients will be admitted the day before the procedure After baseline assessment and laboratory tests they will be randomly assigned to one of two groups One group will receive 12 hours infusion of 154 meql 09 sodium chloride at a rate of 1mlkg per hour before cardiac catheterization and NAC 600mg x 2d PO the day before and the day of the procedure
The second group will receive 154meql sodium bicarbonate in 5 dextrose in water mixed by the nursing staff by adding 154 ml of 1000 meql sodium bicarbonate to 846 ml of 5 dextrose in water slightly diluting the dextrose concentration to 423The initial IV bolus will be 3 mlkg for one hour before cardiac catheterization Following this bolus patients will receive the same fluid at a rate of 1 mlkg per hour during the contrast exposure and for 6 hours after the procedure
A basic panel of blood chemistries Na K Cl Ca P BUN creatinine total protein albumin complete blood count pH HCO3 pCO2 and O2 sat will be obtained before the procedure and post-procedure day 1 and 2 and until any increase of serum creatinine is resolved GFR will be calculated by MDRD formula in all patients before cardiac catheterization
5 Patient selection
Patients will be identified as study candidates based on preliminary laboratory tests results They will referred from the clinics of Shaare Zedek Kupot Cholim and the inpatient services of Shaare Zedek Medical Center Eligible patients include individuals aged 18 year or older with GFR 15-60mlmin calculated by MDRD formula who were scheduled to undergo cardiac catheterization During the randomized study consecutive eligible patients scheduled for exposure to the nonionic radiographic contrast agent iopamidol 796 mOsmkg H2O 755 mg of iopamidol per milliliter and 370 mg iodine per milliliter will be considered for enrollment
6 Exclusion criteria
i Serum creatinine levels more than 8mgdl or GFR less than 15mlmin
ii Change in serum creatinine levels of ³05mgdl during the previous 24 hours
iii Preexisting dialysis
iv Multiple myeloma
v Pulmonary edema
vi Uncontrolled hypertension treated systolic blood pressure more than 160 mmHg or diastolic blood pressure more than 100mmHg
vii Emergency catheterization
viii Recent exposure to radiographic contrast within two days of the study
ix Allergy to radiocontrast
x Pregnancy
xi Administration of dopamine mannitol or NAC before the study
7 Blinding
The study will be completely blinded The serum creatinine level will be determined in a fully blinded fashion by laboratory personnel The investigators from the Nephrology service will analyze the laboratory data without knowledge of patient study groups The patients will not know to which group they will be randomized The investigators from the Cardiology service will know the patient study groups but will not analyze the patients laboratory tests results
8 Study Methods
Qualified patients who agree to enter the study will be assigned to 1 of 2 treatment groups based on a computer-generated randomization schedule Patients allocated to the sodium chloride-NAC group will receive 154mEqL of sodium chloride at a rate of 1mlkg per hour for 12 hours before cardiac catheterization and NAC 600mgx2d PO the day before and the day of the procedure Patients allocated to the sodium bicarbonate group will receive 154 mEqL of sodium bicarbonate in dextrose and H2O mixed by the Nursing Service by adding 154 mL of 1000 mEqL sodium bicarbonate to 846 mL of 5 dextrose in H2O slightly diluting the dextrose concentration to 423
After appropriate nursing evaluation and initial measurement of blood pressure and weight the pre-contrast fluid will be administered Patients allocated to the sodium chloride-NACgroup will receive 154 mEqL of sodium chloride at a rate of 1mlkg per hour for 12 hours before cardiac catheterization and NAC 600mgx2d PO the day before and the day of the procedure The initial intravenous bolus in the NaHCO3 group will be 3 mLkg per hour for 1 hour immediately before radiocontrast injection Following this patients will receive the same fluid at a rate of 1 mLkg per hour during the contrast exposure and for 6 hours after the procedure For patients weighing more than 110 kg the initial fluid bolus and drip will be limited to those doses administered to a patient weighing 110 kg Diuretics will be routinely withheld on the day of contrast injection A basic panel of blood chemistries Na K Cl Ca P BUN creatinine total protein albumin complete blood count serum pH HCO3 pCO2 and O2 sat will be obtained before the procedure and post-procedure days 1 and 2 and until any increase of serum creatinine is resolved GFR will be calculated by MDRD formula before the procedure
9 Study End Points and Statistical Analysis
The primary outcome measure is development of contrast-induced nephropathy defined by an increase in serum creatinine of 25 or more within 2 days after cardiac catheterization This definition is identical to that used in a recent large meta-analysis in contrast-induced nephropathy Post-contrast creatinine will be assessed the mornings of days 1 and 2 The highest serum creatinine on post-contrast days 1 or 2 will be used to calculate the change in serum creatinine the primary end point
Before beginning the study we estimated the sample size needed for the primary end point of contrast-induced nephropathy Based on our own and other previous data we assumed the development of contrast-induced renal failure in 15 of the sodium chloride-NAC group and 5 of the sodium bicarbonate group Analysis indicated that a sample size of 281 patients would be required to detect a statistically significant difference with a power of 80 two tailed p 005
Tests for significance will be conducted using the t test for continuous variables and c2 or Fisher exact test for categorical variables All analyses will be conducted using SAS software version 82 SAS Institute Inc Cary NC Data will be expressed as mean SD All tests will be 2-tailed with differences reported as significant if p 005
10 Feasibility of the study
The average number of cardiac catheterizations performed in Shaare Zedek Medical Center is 25-30 procedures per week A recent review of 30 consecutive cardiac catheterization patients showed that 8 would be eligible for enrollment in this protocol Thus it should take about 10-12 months to enroll the required number of patients
11 Safety
The infusion of sodium bicarbonate and sodium chloride is safe In the published sodium bicarbonate study bolus administration of hydration fluids caused a moderate increase in both systolic and diastolic blood pressure mean 11mm Hg in the sodium chloride group and 14 mmHg in the sodium bicarbonate group No patients developed clinical heart failure or respiratory distress Since the patients enrolled in our study should have controlled hypertension patients with blood pressure more than 160100 will be excluded this mild elevation in blood pressure should not be problematic
12 Study significance
Contrast induced nephropathy is a common complication of cardiac catheterizations Prophylactic hydration with sodium chloride and NAC which is currently in use is less effective in patients with advanced renal disease and the observed incidence of acute contrast induced nephropathy is approximately 15 In addition the use of this regimen requires preventive hospitalization and may be especially problematic in patients with chronic kidney disease when they require urgent cardiac catheterization If preventive hydration with sodium bicarbonate is as effective or better than the currently used saline-NAC regimen the pretreatment time for cardiac catheterization could be significantly shortened hence permitting its usage before emergent procedure Since emergent procedures preclude the use of current relatively long pretreatment regimens bicarbonate could reduce the incidence of acute contrast induced nephropathy in this highly vulnerable group
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None