Clinical trial NCT02046135
Conditions: Acute Kidney Injury Congenital Heart Disease
Keywords: Pediatric Sodium bicarbonate Acute kidney injury Cardiac surgery
Sponsor: Northwell Health
Start date: 2013-09-01; Completion date: 2017-07-22
Enrollment: 51 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The proposed study will investigate the effect of sodium bicarbonate on the prevention of acute kidney injury in children undergoing cardiac surgery with cardio-pulmonary bypass. The investigators hypothesize that the occurrence of acute kidney injury will be less in children treated with sodium bicarbonate in the perioperative period when compared to placebo. The specific aims of this proposal are as follows:

1\. To institute a prospective, randomized, double-blinded, placebo-controlled trial in pediatric subjects undergoing cardiac surgery to determine the efficacy of sodium bicarbonate on prevention of acute kidney injury as measured by pRIFLE criteria. 2. To examine whether treatment with sodium bicarbonate modifies the duration of acute kidney injury, fluid balance, hospital length of stay, need for dialysis, and progression to kidney failure. 3. To determine the relevance of NGAL as a biomarker to predict development of acute kidney injury.

Detailed description:

Arms: arm 1: At the start of the surgery, the patient will receive NaHCO3 as a continuous infusion of D5% 1/3NS + 100 meq/L NaHCO3 + 20 meq/L KCl at maintenance IVF (solution contains \~154 meq of sodium which is equivalent to normal saline). The NaHCO3 infusion will continue for the first 24 hours after the discontinuation of CPB. After 24 hours of receiving the NaHCO3 infusion, the IVF administered to the patient will be the standard solutions used in the PICU at CCMC. arm 2: At the start of surgery, patients in the control arm will receive D5% Normal Saline + 20 meq/L KCl at maintenance IVF. After 24 hours, standard IVF, not containing NaHCO3 or Na acetate will be administered for the duration of the PICU stay as required, determined by the clinicians primarily caring for the patient postoperatively.
Interventions: intervention 1: Sodium Bicarbonate intervention 2: Sodium Chloride
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents:
Prot_SAP_000.pdf: 
 
 
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Sodium Bicarbonate to Prevent Acute Kidney Injury in Children Undergoing Cardiac Surgery: 
 A Randomized Clinical Trial 
 
Principal Investigator:  James Schneider MD 
Co-Investigators: Christine B. Sethna MD, EdM, Vincent Parnell MD, Peter Silver MD, Nataliya Chorny 
MD and David Meyer MD 
 
PART A.  Specific Aims 
With over 1 million operations a year, cardiac surgery with cardiopulmonary bypass (CPB) appears to be the 
second most common major contributor to acute kidney injury (AKI) in developed countries (1). AKI is a 
common and serious postoperative complication of CPB in children (2, 3). The pathophysiology of AKI is 
complex and not yet completely understood. Multiple causes of AKI after CPB have been proposed and 
include ischemia/ reperfusion, generation of reactive oxygen species (ROS), hemolysis, and activation of 
inflammatory pathways (4,5) To date, no simple, safe and effective intervention to prevent cardiopulmonary 
bypass-associated acute kidney injury in a broad patient population has been found.  Sodium bicarbonate has 
shown promise in animal and clinical studies in the prevention of AKI.   
 
The proposed study will investigate the effect of sodium bicarbonate on the prevention of acute kidney injury in 
children undergoing cardiac surgery with cardio-pulmonary bypass.  We hypothesize that the occurrence of 
acute kidney injury will be less in children treated with sodium bicarbonate in the perioperative period when 
compared to placebo.  The specific aims of this proposal are as follows:   
 
Specific Aims: 
1. To institute a prospective, randomized, double-blinded, placebo-controlled trial in pediatric subjects 
undergoing cardiac surgery to determine the efficacy of sodium bicarbonate on prevention of acute kidney 
injury as measured by pRIFLE criteria.   
2. To examine whether treatment with sodium bicarbonate modifies the duration of acute kidney injury, fluid 
balance, hospital length of stay, need for dialysis, and progression to kidney failure.  
3. To determine the relevance of NGAL as a biomarker to predict development of acute kidney injury. 
 
 
PART B.  Significance, Background and Preliminary Studies 
Acute Kidney Injury 
Acute kidney injury is defined as the abrupt onset of renal dysfunction resulting from injurious endogenous or 
exogenous processes characterized by decrease in GFR and increase in serum creatinine.  AKI leads to the 
inability to regulate acid and electrolyte balance and the inability to excrete waste and fluid.  The exact 
incidence of AKI is unknown due to the heterogeneity of definitions of AKI reported in the literature.  Recently, 
the pRIFLE criteria were developed to aid in the definition and classification of AKI in children (6).   
 
In a heterogeneous group of about 3400 critically ill children in a tertiary PICU, Schneider et al. (Principal 
Investigator) identified AKI in about 10% of patients (2).   AKI was found to be independently associated with 
prolonged PICU length of stay as well as length of mechanical ventilation.  Further, AKI was independently 
associated with mortality, worsening with increasing degree of AKI.  
 
Acute kidney injury is a common complication after cardiac surgery under cardiopulmonary bypass.  In a 
retrospective chart review of 458 pediatric (<18 years of age) patients undergoing corrective surgery for 
congenital heart defects at Cohen Children’s Medical Center of New York between 2006 and 2009, we 
demonstrated that 51% of patients developed AKI during their postoperative stay in the pediatric intensive care 


 
 
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2 
unit.  The incidence was even greater when limiting the analysis to neonates (<30 days of life), where 60% of 
patients developed AKI postoperatively (7).  Li, et al, have also shown in a prospective multicenter analysis of 
children undergoing congenital heart corrective surgery that the incidence of AKI is 42%, but significantly 
higher in patients <2 years of age (8).  AKI was identified as an independent risk factor for prolonged ICU and 
hospital length of stay as well as prolonged mechanical ventilation (7,8). To date, though, no study has 
identified a particular intervention or series of interventions (bundles) that can limit the development of this 
independent risk factor for poor outcomes in children undergoing CPB for corrective heart surgery.  Pilot and 
laboratory data suggest that continuous infusion of sodium bicarbonate can decrease the incidence of AKI after 
adult CPB (9) or laboratory animal models of renal injury (10). 
 
Sodium Bicarbonate 
Acidic urine may enhance the generation and toxicity of reactive oxygen species (ROS) generated by 
cardiopulmonary bypass. The beneficial effect of increasing tubular pH by urinary alkalinization, achieved for 
example with the use of sodium bicarbonate infusion, was protective in a rat model of acute renal failure (10).  
Report from a pilot double-blind, randomized controlled clinical trial conducted by Haase et al. suggested that 
sodium bicarbonate infusion with preoperative intravenous loading to achieve urinary alkalinization attenuates 
incidence of AKI associated with CPB in cardiac surgical patients (9). The findings of this pilot study justify 
further investigation provided by government sponsored clinical trials.  In contrast, Herringlake et al found in a 
retrospective cohort study, that bicarbonate loading did not alter the incidence of AKI in adults (11).  This study 
had several limitations. Given the extensive co-morbidities found in adults, it is quite possible that an 
intervention found not to be effective in the adult population would be effective in the pediatric population.  
Accordingly, we hypothesize that urinary alkalinization might protect kidney function in pediatric patients at 
increased risk of acute renal dysfunction undergoing cardiopulmonary bypass.   
 
Further evidence for the beneficial effect of sodium bicarbonate is the data concerning the prevention of AKI 
due to IV contrast.  Increasing urinary pH - in combination with N-acetylcysteine (12) or without (13) - has been 
reported to attenuate acute renal dysfunction in patients undergoing contrast- media infusion.  In a recent 
meta-analysis of 19 clinical trials consisting of 3,609 patients, pre-procedural hydration with sodium 
bicarbonate was associated with a significant decrease in the rate of contrast induced AKI (odds ratio [OR] 
0.56; 95% confidence interval [CI] 0.36-0.86; P=0.008).  The authors concluded that sodium bicarbonate-
based hydration is superior to sodium chloride in preventing AKI of patients undergoing exposure to iodinated 
contrast media (14).  
 
 
PART C.  Drug Information 
 
Sodium Bicarbonate (reference Lexicomp 2010-2011) 
Mechanism of Action: Dissociates to provide bicarbonate ion which neutralizes hydrogen ion concentration and 
raises blood and urinary pH. 
 
Dose: Subjects in the intervention arm will receive NaHCO3 as a continuous infusion of D5% 1/3NS + 100 
meq/L NaHCO3 + 20 meq/L KCl at maintenance IVF (1500 ml/m2/day).  The solution contains ~154 meq of 
sodium which is equivalent to normal saline.  The strength of NaHCO3 is based on a dose of150 meq/m2/day.  
Per Lexicomp, the dose for prevention of hyperuricemia secondary to tumor lysis syndrome (urinary 
alkalinization) in infants and children is sodium bicarbonate IV 120-200 mEq/m2/day diluted in I.V. fluids of 
3000 mL/m2/day.  3000 ml/m2/day is two times normal maintenance IVF.  Given that this protocol is for cardiac 
patients, there is a risk of fluid overload with two times maintenance IVF. Therefore, we have chosen a lower 
dose of sodium bicarbonate 150 meq/m2/day to be diluted in one times maintenance IVF (1500 ml/m2/day).  
The study drug will be obtained from the CCMC pharmacy.  This dosing regimen will be tested in the first 10 
subjects, see Section V.g.        
 
Dosage Forms:  Injection, solution: 4.2% [5 mEq/10 mL] (10 mL); 8.4% [10 mEq/10 mL] (50 mL) Neut®: 4% 
[2.4 mEq/5 mL] (5 mL) [contains edetate disodium]  1 mEq NaHCO3 is equivalent to 84 mg; each g of NaHCO3 


 
 
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provides 12 mEq each of sodium and bicarbonate ions; the osmolarity of 0.5 mEq/mL is 1000 mOsm/L and 1 
mEq/mL is 2000 mOsm/L 
 
Monitoring Parameters: Serum electrolytes including calcium, urinary pH, arterial blood gases  
 
Pharmacodynamics: Onset of action: I.V.: Rapid   Duration:  I.V.: 8-10 minutes 
 
Pharmacokinetics:  Elimination: Reabsorbed by kidney and <1% is excreted in urine 
 
 
PART D.  Experimental Design and Methods 
 
I.  Overview of Study Design 
A prospective, randomized, double-blinded, placebo-controlled trial in children undergoing cardiac surgery with 
cardio-pulmonary bypass will be conducted to determine the effect of sodium bicarbonate on the prevention of 
acute kidney injury.  A total of 132 subjects will be enrolled (66 subjects in each arm) at a single pediatric 
tertiary hospital, Cohen Children’s Medical Center of New York, over a two year time period.   
 
Treatment Arm:  At the start of the surgery, the patient will receive NaHCO3 as a continuous infusion of D5% 
1/3NS + 100 meq/L NaHCO3 + 20 meq/L KCl at maintenance IVF (solution contains ~154 meq of sodium 
which is equivalent to normal saline).  The NaHCO3 infusion will continue for the first 24 hours after the 
discontinuation of CPB. After 24 hours of receiving the NaHCO3 infusion, the IVF administered to the patient 
will be the standard solutions used in the PICU at CCMC. 
 
Control Arm: At the start of surgery, patients in the control arm will receive D5% Normal Saline + 20 meq/L KCl 
at maintenance IVF.  After 24 hours, standard IVF, not containing NaHCO3 or Na acetate will be administered 
for the duration of the PICU stay as required, determined by the clinicians primarily caring for the patient 
postoperatively. 
 
Primary Outcome Measure:  The efficacy of sodium bicarbonate on prevention of AKI will be tested by 
comparing the proportion of subjects in each of the treatment arms who progress to AKI as measured by the 
Pediatric Risk, Failure, Loss of Function, and End-Stage Renal Disease (pRIFLE) criteria or an absolute 
increase in creatinine of 0.3mg/dl.   
 
Secondary Outcome Measures: 
1.  Duration of acute kidney injury 
2.  Cumulative fluid balance 
3.  Hospital and intensive care unit length of stay 
4.  Need for dialysis 
5.  Progression to pRIFLE criteria F  
6.  Association of NGAL as a biomarker to predict development of acute kidney injury 
7.  Length of mechanical ventilation 
8.  Change in acid-base status 
 
II.  Study Sites 
Subjects will be recruited from the Cardiothroacic Surgery Division of the Cohen Children’s Medical Center of 
New York of North Shore-LIJ Health Systems (CCMC) in New Hyde Park, New York  
 
III.  Study Subjects 


 
 
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Patients from CCMC come from a large geographic area with a diverse racial composition. There are currently 
150 children ≤18 years that undergo cardiac surgery with cardiopulmonary bypass per year at CCMC.  
Consecutive patients scheduled for cardiac surgery who meet eligibility criteria will be invited to participate in 
the study.   
 
Eligibility criteria include:   
 
Inclusion Criteria 
1) Subjects age ≤18 years 
2) Subjects scheduled for cardiac surgery with cardiopulmonary bypass 
 
Exclusion Criteria 
1)  Subjects with abnormal creatinine clearance (<90 ml/min/1.7m2) as measured by the Schwartz formula 
2) Subjects with known cystic kidney disease or posterior ureteral valves (subjects with solitary kidney, single 
multicystic/dysplastic kidney, hydronephrosis will not be excluded if renal function is preserved) 
3)  Subjects with known metabolic disorder 
4) Premature infants born <30 weeks gestation and <30 days old due to risk of intraventricular hemorrhage 
 
Subjects in severe cardiogenic shock post-operative requiring extra-corporeal membrane oxygenation (ECMO) 
or left ventricular assist device (LVAD) will be withdrawn from the study. 
 
IV.  Randomization and Blinding 
Subjects will be randomized to the treatment group or control group in a 1:1 ratio to receive sodium 
bicarbonate (treatment group) or placebo (control group).  Allocation will be based on random, computer-
generated numbers in permutated blocks of 10. Study drug and placebo will be prepared and dispensed by the 
pharmacy according to randomization.  The treatment will be administered in an identical fashion to subjects in 
both arms. The investigators involved in the study, clinicians and study subjects will be blinded to the treatment 
assignment.   
 
V.  Study Procedures 
 
The outline of study procedures is as follows: 
 
Study Procedures 
 
Screening  
Pre-
Operative 
 
Intra-
Operative 
2 hr 
4 hr 
12 hr 
24 hr 
 
48 hr 
30 
days 
Review Inclusion/Exclusion Criteria 
x 
 
 
I 
N 
T 
E 
R 
V 
E 
N 
T 
I 
O 
N 
 
 
 
 
 
 
 
Informed Consent/Assent 
x 
 
 
 
 
 
 
 
 
Randomization 
 
x 
 
 
 
 
 
 
 
Demographics/Medical History 
x 
 
 
 
 
 
 
 
 
Height and Weight 
x 
x 
 
 
 
 
 
 
x 
Serum creatinine/BUN 
x 
x 
 
x 
x 
x 
x 
x 
x 
Serum electrolytes  
x 
x 
x* 
x 
x 
x 
x 
x 
x 
Urine pH 
 
x 
x* 
x 
x 
x 
x 
x 
 
CBC with differential 
x 
x 
 
 
 
 
 
 
 
Serum NGAL 
 
x 
 
x 
x 
x 
x 
x 
 
Serum pH 
 
x 
x* 
x 
x 
x 
x 
x 
 
Urine Output Monitoring 
 
x 
x 
x 
x 
x 
x 
x 
 
* Serum and urine pH and serum electrolytes will be done at the discretion of anesthesia and bypass team as per 
protocol. 
Items marked in RED indicate procedures being done specifically for the research study.  Blood draws at 4 hours post-
operatively are standard practice for certain patients, based on complexity of the surgical procedure, and will be done for 


 
 
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research purposes on some patients who had less complex surgeries.  All other procedures represent standard practice 
for all patients undergoing cardiopulmonary bypass for correction of congenital heart lesions. 
 
a.  Screening Visit 
Eligibility and demographic data will be collected on all children scheduled for cardiac surgery with cardio-
pulmonary bypass during the study interval.  Subject and disease characteristics will be recorded for all 
ineligible subjects and those declining participation.  Potential subjects will be screened using the protocol 
inclusion and exclusion criteria. Pre-surgical testing laboratory data, collected as part of standard care, will be 
reviewed.  Study subjects who meet the eligibility criteria will be asked to participate in the study in person by 
physicians known to them in clinic or in the hospital.  Parental/guardian permission (informed consent) and, if 
applicable, child assent, will be obtained prior to any study related procedures being performed.   
 
b. Perioperative Management 
As part of their standard care, subjects will have baseline height, weight, comprehensive metabolic panel, 
complete blood count and serum pH done on the day of surgery at the time of IV and arterial line insertion.  
Subjects will then be randomized into one of the treatment groups and will receive the intervention at the start 
of surgery. 
Clinical practices associated with cardiac surgery will not be modified for the purpose of the study and standard 
of care will be given to all patients.  Intra-operative fluid management will be left to the discretion of the 
anesthesiologist and will be documented.  Intra-operative serum pH will be monitored and subjects may 
receive sodium bicarbonate boluses regardless of treatment group as standard of care if needed (this is done 
infrequently).  As part of the standard practice, all subjects will receive Ancef at the time of surgery and will be 
continued for three doses (vancomycin is used in cases of allergy).  A foley catheter will be placed and urine 
output will be recorded.  Any pre-operative electrolyte disturbances (i.e. hypokalemia, hypernatremia, 
hypocalcemia and acidosis) will be corrected prior to administration of NaHCO3. Serum and serum electrolytes 
will be done during surgery at the discretion of anesthesia and bypass team as per protocol.  Electrolyte 
abnormalities will be treated by the anesthesiologist and will be documented.  
 
c. Intervention 
 
Treatment Arm:  Patients randomized to the intervention of receiving NaHCO3 perioperatively will initially 
receive the current standard anesthetic and perfusion approach at CCMC, which includes a cardiopulmonary 
pump priming solution containing 0.2mEq per milliliter of crystalloid.  At the start of the surgery, the patient will 
begin to receive NaHCO3 as a continuous infusion of D5% 1/3NS + 100 meq/L NaHCO3 + 20 meq/L KCl at 
maintenance IVF (solution contains ~154 meq of sodium which is equivalent to normal saline).  The strength of 
NaHCO3 is based on a dose of 150 meq/m2/day (reference range 120-200mEq/m2/day [Lexicomp, 18th Ed., 
2011-12]) and IVF maintenance of 1500 ml/m2/day. .While the patient is undergoing CPB, calculated base 
deficits more negative than -3 will be corrected by giving NaHCO3 according to the formula: base deficit * 
patient weight in kilograms/ 3.  Tromethamine (THAM) may be used in the neonatal population while 
undergoing CPB if the serum sodium levels have increased to greater than 145 mEq/dL.  Blood gas serum 
sodium, potassium and calcium will be monitored during the surgery and corrections will be made by the 
anesthesiologist. The NaHCO3 infusion will continue for the first 24 hours after the discontinuation of CPB 
(based on current data from CCMC PICU: 85% of patients who develop AKI do so in the first 24 hours, and 
duration of AKI is <48 hours in 75% patients (reference Aydin, Annals of Thoracic Surgery, 2012).  After 24 
hours of receiving the NaHCO3 infusion, the IVF administered to the patient will be the standard solutions used 
in the PICU at CCMC, notably a sodium concentration with dextrose along the spectrum of D5 0.33% NaCl 
through D5 0.45% NaCl, depending on the patient’s serum  electrolyte profile. 
 
Control Arm:   At the start of surgery, patients in the control arm will receive D5% Normal Saline + 20 meq/L 
KCL at maintenance IVF.  The standard approach to perfusion for CPB, including the pump prime solution 
containing NaHCO3 as well as replacement of NaHCO3 for calculated base deficits will be administered as 
described above.  After 24 hours, standard IVF, not containing NaHCO3 or Na acetate will be administered for 


 
 
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the duration of the PICU stay as required, determined by the clinicians primarily caring for the patient 
postoperatively. 
 
d.  Hospital Course 
 
Serum creatinine, NGAL and urine pH will be monitored at 2, 4, 12, 24, and 48 hours. Urine pH will be 
collected and tested by a research nurse from the division of pediatric nephrology according to the study 
outline (see section V.).  The research nurse will be blinded to whether the patients being evaluated are 
enrolled in the control or intervention arms.  Data regarding patient urine pH will be identified by study-specific 
patient number, and stored in a password-protected electronic spreadsheet on the computer of the research 
nurse. Investigators will be blinded to the results of the urine pH, maintaining the double-blinded study design. 
Urinary output will be targeted to maintain urine flow >0.5 ml/kg/hr using furosemide, normal saline bolus and 
ionotropes as necessary. The use of nonsteroidal anti-inflammatory drugs and other nephrotoxic agents such 
as aminoglycosides will be avoided if possible, which is consistent with the standard of care of treating all 
critically ill children.  The use of all medications and fluid boluses will be recorded.   
 
e. Protocol for electrolyte imbalance 
 
Metabolic derangements such as hypernatremia, hypokalemia, hypocalcemia or severe alkalosis will be 
treated as per standard of care in the PICUl. Severe alkalemia, defined as pH>7.6, can be associated with 
ventricular arrhythmias and seizures.  Therefore, any subject with serum pH >7.55 will have the intervention 
fluids immediately discontinued. As per standard of care, electrolytes will be rechecked after any treatment 
intervention. Adverse events such as hypernatremia, hypokalemia and severe alkalosis will be monitored.   
 
f.  Follow up Visit 
 
Subjects will be seen in the outpatient cardiothoracic clinic on Day 30, as is done routinely.  Each subject will 
have height, weight, comprehensive metabolic panel and complete blood count measured as part of the 
research protocol.   
 
g. Pilot study to test dose of Sodium Bicarbonate 
 
To ensure that the chosen dose of sodium bicarbonate adequately alkalinizes the urine, we will briefly halt 
enrollment to blindly review urine pHs of the first 10 randomized subjects.  The research nurse will be blinded 
to the patients’ enrollment arm and the information regarding the results of the urine pH will not be available to 
the investigators until this interim analysis to assure appropriate blinding during the treatment of each patient.  
Since we have blocked randomization in groups of 10, we expect that half of the subjects will receive treatment 
with Sodium Bicarbonate.  Therefore, we expect half of the subjects to have urine pH close to 7.  If we find that 
urine is not adequately alkalinized, we will halt the study and submit a modification to the IRB to alter the dose 
of sodium bicarbonate.   
 
 
VI. Study Outcomes 
 
Demographic and Clinical Data 
The medical record will be abstracted for the following variables: age, gender, diagnosis, previous surgical 
history, race, left ventricular ejection fraction on baseline echo, and current medications.  Surgical parameters 
of cardio-pulmonary bypass time, ischemic time, surgical procedure, surgical complexity score, lowest 
temperature, use of circulatory arrest, use of cerebral perfusion, renal NIRS (measure of oxygen saturation of 
the renal vessels), medications administered, pH range, urine pH, surgical time, post-bypass time, estimated 
blood loss, and blood products administered will be measured.  Cumulative fluid balance (daily Ins and Outs), 
hospital and intensive care unit length of stay, need for and duration of dialysis and medical complications will 
be recorded.   


 
 
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Serum NGAL is a biomarker of early AKI that often increases before serum creatinine.  Specifically for this 
research study, serum NGAL and creatinine level will be drawn at the time of surgery and at 2, 4, 12, 24, and 
48 hours.   
As per routine care, creatinine will then be measured daily.  pRIFLE level will be calculated on the maximum 
creatinine attained.   
 
                                         pRIFLE Criteria 
                    GFR                                                    Urine Output 
Risk         decrease by 25%                                0.5 mL/kg/h for 8 hours 
Injury       decrease by 50%                                 0.5 mL/kg/h for 16hours 
Failure     decrease by 75% or GFR <35            0.3 mL/kg/h for 24 hours or anuric for 12 hours 
 
Loss            Persistent failure 4 weeks 
End stage   End-stage renal disease (persistent failure 3 mo) 
 
Creatinine clearance will be estimated by the Schwartz formula (k x ht (cm)/ creatinine; k= 0.4 premature, k= 
0.55 females and pre-pubertal males <13, k= 0.7 pubertal males).  NGAL will be measured by enzyme-linked 
immunosorbent assay.  Urine pH will be measured at 2, 4, 12, 24 hours post surgery, and as described above, 
the investigators will be blinded to these results.  Serum pH and electrolytes will be measured at 2, 4, 12, 24 
hours.  NGAL and urine pH will be measured specifically for the purpose of performing this research study.  
Serum pH is routinely measured as standard practice in post-operative cardiothoracic surgery patients during 
surgery, and at hours 2, 12, and 24 hours post-operatively.    
 
 
PART E.  Statistical Issues 
 
I.  Statistical Analysis 
Statistical analyses will be done using SPSS 18.0 (SPSS Inc., Chicago, IL) statistical package. A two-tailed p-
value < 0.05 is the criterion for statistical significance.  Intention to treat analysis will be done.  Descriptive 
statistics will be used to characterize outcome measures in subjects.  Means, standard deviations, 95% 
confidence intervals, medians, and minimum and maximum values will be tabulated and reported for all 
continuous variables.  Frequency counts and percentages will be used for categorical variables.  The 
distributions of each outcome will be examined for normality.  Baseline demographic and clinical data of the 
two arms will be examined.  Differences in means in the treatment group will be compared to the control group 
using Student’s t-test, or the Wilcoxon Rank Sum test if the data are not normally distributed.  Differences in 
proportions will be assessed using the chi-square test.  
  
Specific Aims: 
1. To analyze the primary outcome, chi-square will be conducted to compare the proportion of subjects who 
develop AKI by pRIFLE criteria in the two groups.   
2. Student’s t-test or Wilcoxon Rank Sum test for non-normally distributed variables will be used to compare 
values of duration of acute kidney injury, fluid balance, hospital length of stay, need for dialysis, and 
progression to kidney failure between groups.  Pearson correlation and linear regression will be used to 
examine the association between duration of acute kidney injury, fluid balance, hospital length of stay, need for 
dialysis, and progression to kidney failure and development of AKI.  Regression analysis will be adjusted for 
sex, age and race.  Variables may be log transformed to improve the fit of the models.   
 
3.  Pearson correlation and linear regression will be used to analyze the association of NGAL with 
development of AKI.    
  
 


 
 
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II.  Sample Size Estimates 
Sample size estimates were calculated for the primary outcome of proportion that develop AKI in each of the 
two groups.  Sample sizes were considered based on various effect sizes.  Assuming 50% risk of AKI from our 
previous work, a drop from 50% AKI to: 
    35% would need 170 per group 
    30% would need 93 per group 
    25% would need 66 per group 
    20% would need 44 per group  
 
In the literature, studies have used reductions between 20-35%.  We aimed for somewhere in between. The 
comparison of 66 subjects in the treatment group and 66 subjects in the control group provides 80% power (α 
= 0.05) to detect a difference from 0.5 in the control group to 0.25 (that is a 50% reduction in AKI) in the 
treatment group.  nQuery software was utilized to calculate sample size.   
 
III.  Limitations 
The proposed study is limited by the small sample size and heterogenous population.  Given these limitations, 
we believe the results of the proposed study will be able to be generalized to the pediatric cardiac surgery 
population. 
 
PART F.  PROTECTION OF HUMAN SUBJECTS 
 
Risk to Subjects 
a.  Human Subjects Involvement and Characteristics 
The proposed study will involve human subjects, in particular, children and adolescents aged ≤18 years of age.  
The purpose of the study is to examine cardiac surgery in a pediatric population, therefore, other age groups 
are excluded from this study.  Other inclusion/exclusion criteria are listed elsewhere in the protocol.  This 
vulnerable population will be protected.  Assent will be obtained from the participants and participants may 
withdraw from the study at any time. 
 
b.  Potential Risks 
Hypokalemia and hypernatremia are the most common complications.  Administration of bicarbonate to induce 
alkaline diuresis results in alkalemia (an increase in blood pH or reduction in its hydrogen ion concentration).  
Severe alkalemia, pH >7.6 may result in ventricular arrhythmias and seizures. Alkalotic tetany occurs 
occasionally, but hypocalcemia is rare.  Extravasation of concentrated NaHCo3 can lead to tissue necrosis due 
to the hypertonicity of NaHCO3, but concentrated NaHCO3 boluses are not used in this study.  NaHCO3 needs 
to be used with caution in patients with CHF or other sodium-retaining conditions and renal insufficiency. Rapid 
administration of hyperosmotic solution in neonates, infants, and children <2 years of age has led to 
hypernatremia, decreased CSF pressure, and intracranial hemorrhage.  Rapid administration of sodium 
bicarbonate will not be used in this study.  Most data are from premature and very low birthweight babies, 
which have been excluded in this study.  
 
 
Adequacy of Protection of Risk 
a. Recruitment and Informed Consent 
Study subjects who meet the eligibility criteria will be approached in person by physicians in the Cardiothoracic 
Clinic.  Written informed consent from the participant, participant’s parent or legal guardian and assent from the 
patients will be obtained before any study procedure is initiated.  Participants who turn 18 years of age during 
the course of the study will be approached for informed consent.  No study procedure will be continued in 
these participants unless informed consent is obtained.  No advertisements will be used for recruitment of renal 
transplant patients.   
 
b. Protection Against Risk 


 
 
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We will monitor for clinical adverse events throughout the study.  We will report promptly report all 
unanticipated problems related to research to the IRB. Refer to DSMB section for specifics. Participation in all 
areas of the study is completely voluntary.  Should the subjects become intolerant of any aspect of the study, 
their participation (or the specific procedure) will be discontinued. Subjects in severe cardiogenic shock post-
operative requiring extra-corporeal membrane oxygenation (ECMO) or left ventricular assist device (LVAD) will 
be withdrawn from the study. Study investigators will be responsible for communicating to subjects’ information 
arising from the study (on harm or benefit), or from other research on the same topic, that could affect subjects’ 
willingness to continue the study.  All other aspects of the study will be kept confidential.  Data will be stored in 
a locked cabinet and password protected file.   
 
c.  Potential Benefits to Subjects and Others 
One group might receive more effective treatment and/or have fewer side effects than the other treatment 
groups. This study has considerable future potential benefit for all children with cardiac surgery in preventing 
AKI.   
 
d.  Data Collection and Management 
The Investigators are responsible for data management and accuracy of records.  Data will be kept in a secure 
location in an office in the PICU.  Each patient will have a separate folder with all data collected within.  All data 
will be entered into a database by an investigator or study coordinator with unique identifiers attached to each 
patient.  Data will be encrypted and password protected.  
 
e.  Confidentiality 
All data and records generated during this study will be kept confidential in accordance with Institutional 
policies and HIPAA on subject privacy and that the Investigator and other site personnel will not use such data 
and records for any purpose other than conducting the study.   
 
In order to keep protected health information from disclosure, subjects will be assigned unique identifiers 
known only to IRB approved study personnel.. 
 
Storing Documents in Hard Copy 
If you are storing documents in hard copy:  
Any documents that contain subjects’ PHI (e.g., consent forms) will be stored in a locked cabinet within the 
office of study investigator’s in the PICU, separately from any de-identified research data. IRB approved 
personnel will be the only individuals with access to the research data. 
 
. 
 
Storing Documents Electronically 
Any documents containing subjects’ PHI will be stored in a password protected computer document/database 
that will be stored on a password protected computer network, separately from any de-identified research data 
files. IRB approved personnel will be the only individuals with access to subjects PHI. De-identified data files 
will be stored on a password protected computer network.  
 
Storing Documents on Portable Electronic Devices 
No research data containing PHI will be stored on any Portable Electronic Devices (e.g., laptops, tablets, flash 
drives, etc.) 
 
Emailing Data 
Any research data that will be emailed will be de-identified and encrypted. PHI will not be emailed to any 
commercial email addresses (e.g., gmail, yahoo, hotmail, etc.) 
 
Storing Samples/Specimens 


 
 
Version Date 7/15/13 
 
10 
Participant samples/specimens will de-identified and stored with the subject’s study ID number in a locked 
freezer located in the PICU.  
 
The information collected as part of this study will be retained for at least 10 years after the study is completed. 
At that time, the research information will either be destroyed or all the information that identifies the subject 
will be removed from the study results and the key destroyed.    
 
PART G.  INCLUSION OF WOMEN AND MINORITIES 
All subjects who meet the above inclusion criteria will be invited to participate in the study regardless of gender 
or race.  The study will include females and minorities consistent with the demographics of the program.   
 
PART H.  DATA AND SAFETY MONITORING PLAN 
An independent reviewer who is an experienced investigator not directly involved in the study will monitor the 
safety of this study.  The reviewer will review the study when ¼, 1/2 , and ¾ th of the study population are 
enrolled. The independent reviewer will review adverse events, make recommendations concerning 
continuation or conclusion of the study, protection of the confidentiality of the trial data and the results of 
monitoring, review of data and study quality. 
 
PART I.   Payment to Subjects/Families 
Subjects will not be compensated taking part in this study.   
 
PART J.  Publication Policy 
We plan to publish the results (positive or negative) of this study in academic journals and/or national 
meetings.  We will not disclose protected health information about this study.  Any proven evidence of 
falsification of data will be dealt with to take appropriate action against such unacceptable procedures.   
 
PART K.  Conflict of Interest  
James Schneider (PI), has no conflict of interest to disclose with respect to this research study. 
 
PART L.  References 
 
 
1. Uchino S, Kellum JA, Bellomo R, et al: Acute renal failure in critically ill patients: a multinational, multicenter 
study. JAMA 
2005;294:813–818. 
 
2. Schneider J, et al: Acute Kidney Injury after Surgery for Congenital Heart Disease Acute Kidney Injury. 
Critical Care medicine, 2010 
 
3. Skippen PW, Krahn GE: Acute renal failure in children undergoing cardiopulmonary bypass. Cit Care 
Resusc 2005;7:180–187. 
 
4.  Rosner MH, Okusa MD: Acute kidney injury associated with cardiac surgery. Clin J Am Soc Nephrol 
2006;1:19–32. 
 
5. Bonventre J, et al: Cellular pathophysiology of ischemic acute kidney injury J Clin Invest. 2011 November 1; 
121(11): 4210–4221.  
 
6. Akcan-Arikan A et al.   Modified RIFLE criteria in critically ill children with acute kidney injury.  
Kidney Int. 2007 May;71(10):1028-35.  
 
7.  Aydin et al., Annals of Thoracic Surgery, in print 


 
 
Version Date 7/15/13 
 
11 
8.  Li, et al,  Incidence, risk factors, and outcomes of acute kidney injury after pediatric cardiac surgery: a 
prospective multicenter study.  Critical Care Medicine, 2011 
9. Haase et al. Sodium bicarbonate to prevent increases in serum creatinine after cardiac surgery: a pilot 
double-blind, randomized controlled trial. Crit Care Med. 2009 Jan;37(1):39-47. 
 
10.  Atkins JL: Effect of sodium bicarbonate preloading on ischemic renal failure. Nephron 1986;44:70–74. 
 
11.  Herringlake et al.  A perioperative infusion of sodium bicarbonate does not improve renal function in 
cardiac surgery patients: a prospective observational cohort study. Crit Care. 2012 Aug 16;16(4):R156.  
 
12.   Recio-Mayoral A, Chaparro M, Prado B, et al: The reno-protective effect of hydration with sodium 
bicarbonate plus N-acetylcysteine 
in patients undergoing emergency percutaneous coronary intervention: The RENO Study. J Am Coll Cardiol 
2007; 49: 1283–1288 
 
13. Merten GJ, Burgess WP, Gray LV, et al: Prevention of contrast-induced nephropathy with sodium 
bicarbonate: A randomized controlled trial. JAMA 2004; 291: 2328 –2334 
 
14.  Jang et al. Sodium bicarbonate therapy for the prevention of contrast-induced acute kidney injury.  Circ J 
2012; 76: 2255-2265 
 
 
 

ICF_001.pdf: 
Bicarbonate to Prevent AKI During CPB: Intervention 
 
 
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Page 1 of 10 
The Steven and Alexandra Cohen Children’s Medical Center of New York (CCMC) 
Informed Consent and Child Assent to Participate In Research 
Intervention  
 
Protocol Title:   
Sodium Bicarbonate to Prevent Acute Kidney Injury in Children 
Undergoing Cardiac Surgery: A Randomized Control Trial 
Principal 
Investigator: 
 
Institution: 
James Schneider, M.D. 
 
 
Cohen Children's Medical Center of New York  
North Shore Long Island Jewish Health System  
269-01 76th Avenue  
New Hyde Park, NY 11040 
Emergency 
Contact: 
James Schneider, MD  Pager : 917-448-0622 
  
 Introduction 
You are being asked to join a research study. The purpose of a research study is to answer 
specific questions, sometimes about the safety of a drug or device and how well it works.  Being 
in a research study is different from being a patient.  When you are a patient, you and your 
doctor have freedom in making decisions about your healthcare.  When you are in a research 
study, the researcher will follow the rules of the research study as closely as possible, while 
monitoring your health. 
 
This consent form will explain: 
 the purpose of the study 
 what you will be asked to do  
 the potential risks and benefits 
 
It will also explain that you do not have to be in this study to receive medical care. You should 
ask questions before you decide if you want to participate. You can also ask questions at any 
time during the study.  
 
Why am I being asked to volunteer? 
You are being invited to participate in a research study because your child requires surgery to 
correct a congenital heart lesion (heart problem, such as a hole or abnormally small structures) 
and will require cardiopulmonary bypass (heart-lung machine) during the procedure.  
 
What is the purpose of this research study? 
This study is being done because we are trying to identify a way to prevent injury to the kidney 
that has been associated with undergoing cardiopulmonary bypass.  
 
The purpose of this study is to evaluate whether giving your child sodium bicarbonate prior to 
beginning surgery, and then for the first 24 hours after surgery will protect the kidneys from the 


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effects of cardiopulmonary bypass. Sodium bicarbonate is a common medication used in 
children who are critically ill, and helps to balance any extra acid in the blood that forms during 
critical illness.  Specifically, we will determine if this study will effect (1) the development and 
progression of kidney injury, (2) how long children need to be on a ventilator (breathing 
machine), (3) how long children need to be in the intensive care unit and hospital after surgery 
and (4) whether there is any ongoing kidney injury after hospital discharge. 
 
Most problems of the heart that children are born with can now be corrected by surgery, with 
excellent outcomes.  Children who require cardiopulmonary bypass during surgery for correction 
of congenital heart lesions have a higher risk of developing kidney injury.  Recently, we have 
learned that kidney injury can lead to worse patient outcomes, such as requiring longer times on 
the ventilator (breathing machine) as well as longer times in the intensive care unit and hospital.  
 
We have preliminary information from adult and animal research studies that suggest that when 
patients receive sodium bicarbonate during the time they are on heart-lung bypass during surgery 
and then for the first 24 hours after surgery, kidney injury can be prevented.  There has not been 
any study investigating whether this benefit is recognized in pediatric patients. 
 
How long will I be in the study? How many other people will be in the study? 
You are being asked to allow your child to participate in this study from the time they are 
prepared for surgery in the operating room until 48 hours after completion of cardiopulmonary 
bypass.  If your child is still in the hospital 30 days after surgery then we will also assess his/her 
kidney function as well as height and weight.  The purpose of this 30-day review is to check for 
late occurring problems with kidney function. 
 
We plan to enroll almost 200 children (between birth and 18 years of age) in our pediatric 
intensive care unit at Cohen Children’s Medical Center of New York. 
 
What am I being asked to do? 
If you agree to allow your child to participate in the research study, general medical history 
information as well as height and weight will be collected during the screening visit with the 
cardiothoracic surgeons.   
 
On the day of surgery, blood and urine samples will be collected at the time the IV line is placed 
(which is necessary for the surgery to be done).  The IV line, or intravenous line, is the small 
plastic tube placed inside your child's vein with a needle poke in order to provide medication 
during and after surgery.   
 
The only medical procedures being done for the purposes of this research study are giving you 
the sodium bicarbonate solution, collecting urine samples more frequently (although the catheter 
placed in the bladder to collect urine is standard of care for all surgical patients), and, for some 
patients, 1 extra blood draw (maximum 1-2 milliliters or less than ½ teaspoon) 4-hours after 
surgery. 
 
If after the first visit, it is determined that your child is eligible for the study, on the day of 
surgery, your child will be randomly placed into one of two groups: 1) control group or 2) 


Bicarbonate to Prevent AKI During CPB: Intervention 
 
 
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intervention group.  Randomization means that you will be assigned to a group by chance ( like 
flipping a coin) You will have an equal chance of being in either (or any) group. The study is 
done this way because knowing whether you are in a group can change the results of the study.  
We will not tell you which group you are in. The research study staff will not know your group 
either. We can quickly find out which group you are in if we ever need to know for your safety. 
 
The control group will receive a placebo via the IV line in the form of a normal saline solution 
(sodium chloride) during surgery and in the intensive care unit after surgery. This is considered 
appropriate care according to the anesthesia team, cardiothoracic surgery team, as well as the 
intensive care unit team who will care for your child. The placebo is a liquid solution that looks 
like the study drug but has no real medicine in it. A placebo is often used in research studies so 
that the doctor and you do not know your study group.  The study is done this way because 
knowing whether you are getting the study drug can change the results of the study.  
 
The intervention group will receive sodium bicarbonate continuously through the IV at the 
beginning of anesthesia, which will continue for the first 24 hours after surgery.  After 24 hours 
of receiving the sodium bicarbonate continuously, the IV fluids will be changed to the standard 
solutions used in the Pediatric Intensive Care Unit at CCMC.   
 
This is a double-blinded study.  Double blinding is when neither the researcher nor the people in 
the study know which study group a person is in. It is used to make sure the study data will not 
be biased.  The physicians and nurses caring for your child in the operating room and the PICU 
will not be aware of which solution your child will be receiving during the first 24 hours after 
surgery. In case of an emergency, we can find out if you are getting the placebo or the 
medication. 
 
Standard of care will be maintained regarding checking for abnormal blood tests and will be 
treated according to standard practice.   
 
What are the possible risks or discomforts?  
Potential short-term risks or discomforts linked to the use of sodium bicarbonate in children 
undergoing open heart surgery are: 
 Hypokalemia (low blood potassium). In severe cases, this could lead to heart rhythm 
abnormalities, and in turn could affect blood pressure. 
 Hypernatremia (high blood sodium). In severe case, this can lead to fluid retention. You 
might notice a swollen appearance. 
 Alkalemia (blood pH >7.40): severe alkalemia can cause heart rhythm abnormalities, 
neurologic changes such as an alteration in the level of consciousness,  and  the blood 
calcium level to decrease, which can lead to a rare condition known as tetany (rigid 
muscles). 
 Leaking out of sodium bicarbonate solution from the IV line into the body tissue at high 
concentrations can lead to tissue injury, although this is extremely unlikely because the 
type of bicarbonate fluid used in this study is not strong enough to cause this 
complication. 
 


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The group that does not receive the sodium bicarbonate may have more side effects than the 
other group. 
 
We will try to decrease these potential risks by closely monitoring for clinical adverse events 
throughout the study according to standard blood laboratory tests and treating abnormal blood 
tests according to standard practice.  
 
Any time confidential information is collected, there is a risk that information will be 
unintentionally released. Any information about you or your child obtained from this research 
will be kept as confidential (private) as possible.  
 
All paper records related to your/your child’s involvement in this research study will be stored in 
locked file cabinets. Computerized records are password protected. Your/your child’s identity on 
these records will be indicated by a case number rather than by name, and the information 
linking these case numbers with your/your child’s identity will be kept separate from the 
research records.  
 
What if new information becomes available about the study? 
During the course of this study, we may find more information that could be important to you 
and/or your child. This includes information that, once learned, might cause you to change your 
mind about your child being in the study. We will notify you as soon as possible if such 
information becomes available. 
 
What are the possible benefits of the study?  
We cannot and do not guarantee or promise that you or your child will receive any benefits from 
this study. Possible benefits of study participation include shorter time on the ventilator, less 
need for dialysis (kidney replacement therapy), and shorter time in the intensive care unit and 
hospital, related to the decreased development of acute kidney injury. 
 
Future children who require cardiopulmonary bypass (heart-lung machine) for open-heart 
surgery and their families may benefit from this study, which will provide a better understanding 
of how to limit the risk of developing kidney injury during and after open-heart surgery. 
 
What other choices do I have if I do not participate?  
If you choose not to participate, your child’s care team will still do what they think is best for 
your child, but they will not follow the fluid management guideline. Your child’s information 
will not be collected.   
 
Will I be paid for being in this study? 
Neither you nor your child will be paid for being in this study.  
 
Will I have to pay for anything? 
There will be no cost to you for your child to be in this research study.  Care that would be given 
if your child was not in this research study, such as the surgery and routine tests post-operatively, 
will be charged under your usual payment method.  There will be no charge to you or your 
insurance company for any of the costs directly related to this study. 


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What are your rights as a research participant? 
Your participation in this project is voluntary. The quality of your medical care will be the same, 
whether you join, refuse to join, or decide to leave the study. 
 
If you do not join the study you will not be penalized or lose benefits to which you are entitled. If 
you join the study you may withdraw at any time without prejudice to your future care at the 
North Shore-LIJ Health System. Follow-up examinations may be needed to assure your well-
being.   
 
Could you be taken off the study before it is over? 
It is also possible that your participation in this study may end without your consent.  This 
decision may be made by a researcher, study sponsor, or the Institutional Review Board (IRB- 
the committee that oversees research at this institution).    
 
Reasons for withdrawal may include:   
 failure to follow instructions,  
 failure to show up for study visits,  
 it is not in your best interest to continue on this study, or  
  the study is stopped.   
 
If you withdraw from this study or if you are withdrawn from the study, any data (or samples) 
already collected will continue to be used.  However, no new data will be collected.   
 
For your safety, if you withdraw or are withdrawn from this study, you are urged to return for 
final testing to evaluate the function of your kidneys.  
 
What happens if I am injured or hurt during the study? 
All forms of medical diagnosis and treatment involve some risk of injury. In spite of all 
precautions, you or your child might develop an injury from participating in this study.   
 
If your child is hurt from being in the study, you will receive medical care and treatment as 
needed from the Steven and Alexandra Cohen Children’s Medical Center of New York (CCMC). 
However, you will be responsible for the costs of such medical treatment, directly or through 
your medical insurance and/or other forms of medical coverage. No money will be given to you. 
 
If costs of care related to such an injury are not covered by your insurer, managed care plan or 
other benefits program, you may be responsible for these costs. If you are unable to pay for such 
costs, our research staff will assist you in applying for supplemental benefits and explain how to 
apply for patient financial assistance from the hospital. 
 
Additionally, we are not responsible for research and medical care by other institutions or 
personnel participating in this study. You do not waive any liability rights for personal injury by 
signing this form. 
 
 


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When is the study over?  Can I leave the study before it ends? 
If you decide to participate, you are free to leave the study at anytime. Withdrawal will not 
interfere with your or your child’s future care.  
 
This study is expected to end after all information has been collected and reviewed. This study 
may also be stopped at any time by your child’s doctor or the study Principal Investigators 
without your consent because it is necessary for your or your child’s health or safety. Such an 
action would not require your or your child’s consent, but you will be informed if such a decision 
is made and the reason for this decision.  
 
Who can see or use my information?  How will my personal information be protected?  
Privacy/Confidentiality (HIPAA Authorization Section) 
If you agree to be in this study, we will collect health information that identifies you. We will 
collect the results of tests, questionnaires and interviews. We will also collect information from 
your medical record. We will only collect information that is needed for the research. This 
information has been described in this consent form. If you sign this consent form, you are 
giving us permission to collect, use and share your health information. This permission is called 
authorization. 
Study records that identify you will be kept private. You will not be identified in study records or 
publications disclosed outside the North Shore-Long Island Jewish Health System, except as 
detailed below.  
Investigators will share the results of your study tests and procedures with clinical staff not 
involved in the study who may be involved in your treatment.   
In addition, your records may be reviewed in order to meet federal or state research regulations.  
Reviewers may include representatives from government agencies such as the Food and Drug 
Administration and representatives from the North Shore-Long Island Jewish Health System 
Institutional Review Board (IRB – the committee that reviews research at this institution).  
If your research record is reviewed by any of these groups, they may also need to see your entire 
medical record.  Please be aware that once private information is disclosed, it is subject to re-
disclosure by the recipient and can no longer be considered protected. 
If your research records are used for decisions related to your clinical care, then you have the 
right to review this information and request changes.  This is limited to information about your 
treatment, and does not include information related to procedures or tests that are for research 
purposes only. You may access this information only after the study analysis is complete. You 
have the right to know who has and who will see your records.  To request this information, or 
for any questions related to your health information, you may contact the Research Privacy 
Officer at 516-562-2018. 
 
If you change your mind about being in the study, you may withdraw at any time. If you want us 
to stop collecting your health information, you need to send a letter to the researcher at the 


Bicarbonate to Prevent AKI During CPB: Intervention 
 
 
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Page 7 of 10 
following address: 
 
James Schneider, MD 
Pediatric Critical Care Medicine  
Cohen Children's Medical Center of New York  
North Shore Long Island Jewish Health System  
269-01 76th Avenue  
New Hyde Park, NY 11040 
 
Your letter needs to say that you have changed your mind and do not want the researcher to 
collect and share your health information. You may also need to leave the research study if we 
cannot collect any more health information. We may still use the information we have already 
collected. We need to know what happens to everyone who starts a research study, not just those 
people who stay in it. 
 
The information that is collected for research will be analyzed for many years and it is not 
possible to know how long this analysis and follow-up will take. Therefore, you are allowing 
access to this information indefinitely. 
 
Data from this study may be used in medical publications or presentations. The information will 
be de-identified so that individual subjects cannot be recognized and the information will no 
longer be considered Protected Health Information (PHI). 
 
If the researchers learn about potential serious harm to you or someone else or other public 
health concerns, it will be shared with the appropriate authorities. 
 
Who can I call with questions, complaints or if I’m concerned about my rights as a 
research subject? 
If you have questions, concerns or complaints regarding your child’s participation in this 
research study or if you have any questions about your child’s rights as a research subject, you 
should speak with one of the Principal Investigators listed on page one of this form.  If a member 
of the research team cannot be reached or you want to talk to someone other than those working 
on the study, you may contact the Office of the Institutional Review Board (the committee that 
oversees research at this institution) by calling (516) 562-3101. 
 
When you sign this form, you are agreeing to take part in this research study. This means that 
you have read the consent form, your questions have been answered, and you have decided to 
volunteer.  Your signature also means that you are permitting the Steven and Alexandra Cohen 
Children’s Medical Center of New York (CCMC) to use your child’s personal health information 
collected for research purposes within our institution. You are also allowing the Steven and 
Alexandra Cohen Children’s Medical Center of New York (CCMC) to disclose that personal 
health information to outside organizations or people involved with the operations of this study. 
 
A copy of this informed consent will be given to you.  
 
SIGNATURE PAGE FOLLOWS 


Bicarbonate to Prevent AKI During CPB: Intervention 
 
 
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Summation/Signature 
You have read the above description of the research study. You have been told of the risks and 
benefits involved and all your questions have been answered to your satisfaction. A member of 
the research team will answer any future questions you may have. You voluntarily agree to join 
this study and know that you can withdraw from the study at any time without penalty. By 
signing this form, you have not given up any of your legal rights. 
 
______________________________       
 
_______________ 
Name of Subject (Please Print)  
 
   
 
Age 
 
 
_______________________________       ______________________________ ________ 
Name of Parent/Legal Guardian                Signature of Parent/Legal Guardian         Date 
(Please Print) 
 
 
______________________  
_____________________________  
__________ 
Witness's Printed Name  
 
Witness's Signature                               
  Date 
(Preferably someone not connected with the research project) 
 
 
 
Investigator’s Statement  
In addition to advising the above subject of other forms of treatment and therapy which are 
appropriate, I have offered an opportunity for further explanation of the risks and discomforts 
which are, or may be associated with this study and to answer any further questions relating to it. 
 
________________________________ 
Name of Investigator 
 
 
_____________________________________________ 
________ 
Investigator’s signature                                                
 Date  
 
 
 
 
 
 
 
 
 


Bicarbonate to Prevent AKI During CPB: Intervention 
 
 
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North Shore-Long Island Jewish Health System 
Campus: Steven and Alexandra Cohen Children’s Medical Center of New York 
Assent to be in a Research Study (8-17 years) 
 
Title: Sodium Bicarbonate to Prevent Acute Kidney Injury in Children Undergoing 
Cardiac Surgery 
 
Why are we meeting with you? 
We want to tell you about something we are doing called a research study.  A research study is 
when people collect a lot of information to learn more about something. Some of the people who 
work here are doing a study to learn more about children who have heart surgery and how it may 
affect the kidneys. After we tell you about it, we will ask if you’d like to be in this study or not. 
 
Why are we doing this study? 
Children who need surgery to fix their heart problem need to be placed on a heart-lung machine.  
This may hurt the kidneys.   
We are working in our hospital to see if we can protect the kidneys of children who need heart 
surgery.  We want to find out if a medicine can keep the kidneys safe during surgery.   
 
What will you be asked to do and how long will it take? 
Only if you agree, here’s what will happen: 
 
1. Before surgery, we will collect some information about you.  
 
2. We will pick one-half of the children who agree to be in the study to be given a medication 
during surgery. If you are picked, you will be given the medication and we will watch closely 
to see how your kidneys are working and if any injury occurs. 
 
Will this study hurt? 
Sometimes things that don’t feel good happen in research studies.  Some things that could 
happen may hurt you, make you feel yucky, or make you feel upset.  You might experience 
things like your heart beating funny, may be extra tired feeling, or may have an area of skin 
around an IV site hurt.  Some of the things might happen to you or they might not.  Or things 
might happen that we don’t know about yet.  
 
Will you get better if you are in this study? 
Maybe.  We hope that giving this medication will keep your kidneys healthy.  This study will 
help us answer that question. 
 
Do you have any questions? 
You can ask questions any time. You can ask now. You can ask later. You can talk to me or you 
can talk to someone else.  
 
 
 


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Do you have to be in this study? 
No, you don’t. No one will be mad at you if you don’t want to do this. Please talk to your parents 
about this before you decide whether or not to be in this research study.  We will also ask your 
parents to give their permission for you to be in this study. But even if your parents say “yes,” 
you can still decide not to be in this research study. And, remember, you can say yes now and 
change your mind later.  It’s up to you. We will give you a copy of this form to keep. 
 
************************************************************** 
Putting your name below means that you have decided to be in this study.  You and your parents 
will be given a copy of this form after you have signed it.   
 
_____________________________ 
Name of Subject 
 
_____________________________  
 
_____________________________ 
Sign your name here ↑ 
 
 
 
 
Date 
 
________________________________ 
Name of Investigator Obtaining Assent 
 
__________________________________  
____________________________ 
Signature of Investigator Obtaining Assent  
Date 
 
 
__________________________________  
____________________________ 
Signature of Witness  
 
 
 
Date 
 
 
 
By initialing in the following places, the investigator indicates his/her opinion that the child 
cannot give consent/assent because he/she is: 
 
____Too young at age  ____       
Initials investigator _____ 
 
____Too ill. Explanation below 
Initials investigator _____