Use of Bicarbonate to Reduce the Incidence of Acute Renal Failure After Cardiac Surgery

• Sponsor: Wake Forest University Health Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT00484354
• Collaborator: (none)
• Enrollment: 123
• Location: 1
• Arms: 2
• Duration (Months): 91
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if the incidence of acute renal failure (ARF) in high risk patients who undergo coronary artery bypass grafting (CABG) is reduced by treating patients in the perioperative period with intravenous (IV) sodium bicarbonate. Patients will be randomized in a 50:50 allocation to receive either IV sodium bicarbonate or IV normal saline. The volume of fluid given in each arm of the study is equal. All other interventions in those patients will be according to standard cardiothoracic anesthesia protocol at our institution.

Condition or Disease	Intervention/Treatment	Phase
Kidney Failure, Acute; Renal Replacement Therapy	Drug: Sodium bicarbonate; Other: Normal saline; Other: Bicarbonate; Other: Placebo	Phase 2

Detailed Description

This is a randomized, controlled, single center study in patients felt to be at high risk for ARF following CABG surgery. Patients who have met the selection criteria noted below will be randomized to one of two treatment arms:

1. Patients allocated to the sodium bicarbonate (NaHCO3) arm will receive a 0.150 M NaHCO3 solution prepared in a sterile water base. An initial bolus of 0.150 M NaHCO3 at 5.0 ml/kg will be given over fifteen minutes prior to surgery. Following the bolus, the 0.150 M NaHCO3 infusion will be run at 1.0 ml/kg/hr during the procedure and for six (6) hours afterwards. The NaHCO3 infusion will then be decreased to 0.4 ml/kg/hr for a further twelve (12) hours. The goal in the NaHCO3 arm is to provide a total dose of approximately 2.5-3.0 mEq/kg of sodium bicarbonate. This dose was determined from prior studies and found to lead to a slight increase in the serum bicarbonate level post-operatively. Anecdotally, the metabolic stress of CABG surgery often leads to a decline in the serum bicarbonate level in patients not treated with alkali therapy.

2. Patients allocated to the normal saline (NS) arm will receive an initial bolus consisting of 0.154 M NaCl (NS) at 5.0 ml/kg given over fifteen minutes prior to surgery. Following the bolus, these patients will receive NS (0.154 M) at a rate of 1.0 ml/kg/hour during the procedure and for six (6) hours afterwards. The rate will then be decreased to 0.4 ml/kg/hour for a further twelve (12) hours as done in the NaHCO3 treatment arm above. There will be a maximum rate of infusion of 125 mL/min used in both study arms to avoid volume overload issues in morbidly obese patients.

There will be no other deviation from standard protocol when treating these patients undergoing CABG at our institution. The standard protocol is dictated by both the cardiothoracic surgeons and anesthesiologists involved with each individual case. The purpose of this study is to compare the incidence of ARF (maximal change in SCr) in high risk patients undergoing CABG when treated with either a NS or NaHCO3 maintenance infusion. This study will test the hypothesis that treatment with NaHCO3 may have a protective effect over NS in preventing AFR following CABG in a high risk population.

Study Design

• Study Type: Interventional
• Actual Enrollment: 123 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Reduction of Acute Renal Failure Associated With Cardiovascular Surgery: A Randomized Study Comparing Sodium Bicarbonate to Normal Saline
• Study Start Date: May 1, 2006
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Bicarbonate administration	Drug: Sodium bicarbonate; IV bicarbonate given with amount based on patient weight; Other: Bicarbonate; IV bicarbonate, dosed by weight
Placebo Comparator: 2 Normal saline administration	Other: Normal saline; IV Normal saline with volume given determined by patient weight; Other: Placebo; Normal saline, with volume given based on patient weight

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Developed Acute Kidney Injury Within 72 Hours [72 hours post-operative]

   Number (percentage) of patients who developed acute kidney injury within 72 hours, defined by an increase in serum creatinine level of 0.3 mg/dl from baseline

Secondary Outcome Measures

1. Change in GFR Over 72 Hours Post Operatively [72 hours]

   25% or greater change in serum creatinine level

2. Length of Hospital Stay [Until hospital discharge, up to 30 days]

   Length of hospital stay in days

3. Number of Participants With Need for Dialysis [Until hospital discharge, up to 30 days]

   Number of participants needing dialysis

4. Mortality [Until hospital discharge, up to 30 days]

   Number of patients who died during the hospitalization

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Calculated GFR ≤ 60 ml/min/m2 (MDRD)

OR

• Any combination of two (2) of the following:

• Age ≥ 70

• Complex surgery (any of the following):

• CABG/Valve

• Redo operation

• Deep hypothermic arrest

• ≥ 2 valves

• History of PVD surgery

• EF < 35%

• Presence of diabetes mellitus

• Prior kidney transplant

Exclusion Criteria:

• Age < 18

• Pre-existing ESRD (dialysis patients)

• Pre-op GFR ≤ 15 ml/min/m2

• Pre-op bicarbonate level ≥ 30 mEq/L

• Emergency surgery (unable to effectively consent)

• Pregnancy

• Heart transplant (OHT)

• Aortic surgery (proximal or distal)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wake Forest University School of Medicine	Winston-Salem	North Carolina	United States	27157

Sponsors and Collaborators

• Wake Forest University Health Sciences

Investigators

• Principal Investigator: Michael V. Rocco, MD, Wake Forest University School of Medicine, Dept of Internal Medicine, Division of Nephrology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT00484354
• Other Study ID Numbers: IRB00002409
• First Posted: Jun 8, 2007
• Last Update Posted: Oct 16, 2018
• Last Verified: Sep 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Wake Forest University Health Sciences: Acute Renal Failure; Cardiac Surgery; Sodium Bicarbonate; Length of Stay; Mortality
• Additional relevant MeSH terms: Renal Insufficiency; Acute Kidney Injury

Study Results

Participant Flow

Arm/Group Title	IV Sodium Bicarbonate	IV Normal Saline
Arm/Group Description	IV sodium bicarbonate given with amount based on patient weight	IV Normal saline with volume given determined by patient weight
Period Title: Overall Study
STARTED	64	59
COMPLETED	63	57
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	IV Sodium Bicarbonate	IV Normal Saline	Total
Arm/Group Description	IV sodium bicarbonate given with amount based on patient weight	IV Normal saline with volume given determined by patient weight	Total of all reporting groups
Overall Participants	64	59	123
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70.2 (12.6)	69.7 (13.5)	70 (13)
Sex: Female, Male (Count of Participants)
Female	30 46.9%	16 27.1%	46 37.4%
Male	34 53.1%	43 72.9%	77 62.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	5 7.8%	9 15.3%	14 11.4%
White	57 89.1%	47 79.7%	104 84.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 3.1%	3 5.1%	5 4.1%
Region of Enrollment (participants) [Number]
United States	64 100%	59 100%	123 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Developed Acute Kidney Injury Within 72 Hours
Description	Number (percentage) of patients who developed acute kidney injury within 72 hours, defined by an increase in serum creatinine level of 0.3 mg/dl from baseline
Time Frame	72 hours post-operative

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Sodium Bicarbonate	IV Normal Saline
Arm/Group Description	IV sodium bicarbonate given with amount based on patient weight	IV Normal saline with volume given determined by patient weight
Measure Participants	63	57
Count of Participants [Participants]	17 26.6%	14 23.7%

2. Secondary Outcome

Title	Change in GFR Over 72 Hours Post Operatively
Description	25% or greater change in serum creatinine level
Time Frame	72 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Sodium Bicarbonate	IV Normal Saline
Arm/Group Description	IV sodium bicarbonate given with amount based on patient weight	IV Normal saline with volume given determined by patient weight
Measure Participants	63	57
Count of Participants [Participants]	21 32.8%	21 35.6%

3. Secondary Outcome

Title	Length of Hospital Stay
Description	Length of hospital stay in days
Time Frame	Until hospital discharge, up to 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Sodium Bicarbonate	IV Normal Saline
Arm/Group Description	IV sodium bicarbonate given with amount based on patient weight	IV Normal saline with volume given determined by patient weight
Measure Participants	63	57
Mean (Standard Deviation) [days]	14.2 (15.4)	14.6 (14.4)

4. Secondary Outcome

Title	Number of Participants With Need for Dialysis
Description	Number of participants needing dialysis
Time Frame	Until hospital discharge, up to 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Sodium Bicarbonate	IV Normal Saline
Arm/Group Description	IV sodium bicarbonate given with amount based on patient weight	IV Normal saline with volume given determined by patient weight
Measure Participants	63	57
Count of Participants [Participants]	4 6.3%	5 8.5%

5. Secondary Outcome

Title	Mortality
Description	Number of patients who died during the hospitalization
Time Frame	Until hospital discharge, up to 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Sodium Bicarbonate	IV Normal Saline
Arm/Group Description	IV sodium bicarbonate given with amount based on patient weight	IV Normal saline with volume given determined by patient weight
Measure Participants	63	57
Count of Participants [Participants]	9 14.1%	10 16.9%

Adverse Events

Time Frame	Until hospital discharge, up to 30 days
Arm/Group Title	IV Sodium Bicarbonate		IV Normal Saline
Arm/Group Description	IV sodium bicarbonate given with amount based on patient weight		IV Normal saline with volume given determined by patient weight
All Cause Mortality
	IV Sodium Bicarbonate		IV Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/63 (14.3%)		10/57 (17.5%)
Serious Adverse Events
	IV Sodium Bicarbonate		IV Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/63 (14.3%)		10/57 (17.5%)
General disorders
Mortality	9/63 (14.3%)	9	10/57 (17.5%)	10
Other (Not Including Serious) Adverse Events
	IV Sodium Bicarbonate		IV Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/63 (6.3%)		5/57 (8.8%)
Renal and urinary disorders
Dialysis	4/63 (6.3%)	4	5/57 (8.8%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.