Investigations of the Optimum Serum Bicarbonate Level in Renal Disease.

• ClinicalTrials.gov Identifier: NCT01574157
• Recruitment Status: Completed
• First Posted: April 10, 2012
• Results First Posted: August 28, 2019
• Last Update Posted: August 28, 2019
• Sponsor: VA Office of Research and Development
• Information provided by (Responsible Party): VA Office of Research and Development

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Conditions: Chronic Renal Insufficiency; Diabetes Mellitus
• Interventions: Drug: Sodium bicarbonate; Drug: Placebo
• Enrollment: 74

Participant Flow

Recruitment Details	Participants were recruited from VA Salt Lake City Healthcare System from November 2012 to October 2017.
Pre-assignment Details

Arm/Group Title	Sodium Bicarbonate	Placebo
Arm/Group Description	Participants were prescribed 0.5 meq of sodium bicarbonate per 1 kilogram of lean body weight daily for six months.	Participants were prescribed an identical number of placebo tablets had they been assigned to the intervention, and took this daily for six months.
Period Title: Overall Study
Started	35	39
Month 3	31	33
Completed [1]	31	31
Not Completed	4	8
Reason Not Completed
Withdrawal by Subject	4	5
Lost to Follow-up	0	3
[1] Month 6

Baseline Characteristics

Arm/Group Title		Sodium Bicarbonate	Placebo	Total
Arm/Group Description		Sodium bicarbonate: Participants will receive 0.5 meq of sodium bicarbonate per 1 kilogram of lean body weight daily. The total amount will be divided into twice daily doses.	Placebo: Participants will receive an identical number of placebo tablets had they been assigned to the intervention. Placebo will be divided into twice daily doses and receive this for six months.	Total of all reporting groups
Overall Number of Baseline Participants		35	39	74
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	35 participants	39 participants	74 participants
		70 (8)	73 (8)	72 (8)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	35 participants	39 participants	74 participants
	Female	1 2.9%	1 2.6%	2 2.7%
	Male	34 97.1%	38 97.4%	72 97.3%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	35 participants	39 participants	74 participants
	Hispanic or Latino	3 8.6%	4 10.3%	7 9.5%
	Not Hispanic or Latino	32 91.4%	35 89.7%	67 90.5%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	35 participants	39 participants	74 participants
	American Indian or Alaska Native	1 2.9%	1 2.6%	2 2.7%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	1 2.6%	1 1.4%
	Black or African American	0 0.0%	0 0.0%	0 0.0%
	White	32 91.4%	36 92.3%	68 91.9%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	2 5.7%	1 2.6%	3 4.1%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	35 participants	39 participants	74 participants
		35 100.0%	39 100.0%	74 100.0%
Estimated glomerular filtration rate; Mean (Standard Deviation); Unit of measure: Ml/min/1.73m2
	Number Analyzed	35 participants	39 participants	74 participants
		50 (20)	52 (16)	51 (18)
Systolic blood pressure; Mean (Standard Deviation); Unit of measure: Mm Hg
	Number Analyzed	35 participants	39 participants	74 participants
		129 (12)	127 (11)	128 (12)
Use of angiotensin converting enzyme-inhibitor (ACE-I) or angiotensin receptor blocker (ARB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	35 participants	39 participants	74 participants
		28 80.0%	34 87.2%	62 83.8%
Total body weight; Mean (Standard Deviation); Unit of measure: Kg
	Number Analyzed	35 participants	39 participants	74 participants
		100 (18)	101 (22)	101 (20)
Lean body weight; Mean (Standard Deviation); Unit of measure: Kg
	Number Analyzed	35 participants	39 participants	74 participants
		67 (8)	68 (9)	68 (9)
Congestive heart failure; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	35 participants	39 participants	74 participants
		1 2.9%	4 10.3%	5 6.8%
Serum total carbon dioxide (CO2); Mean (Standard Deviation); Unit of measure: meq/L
	Number Analyzed	35 participants	39 participants	74 participants
		24 (3)	24 (2)	24 (2)
Serum potassium; Mean (Standard Deviation); Unit of measure: meq/L
	Number Analyzed	35 participants	39 participants	74 participants
		4.2 (0.4)	4.3 (0.4)	4.2 (0.4)
Hemoglobin A1c; Mean (Standard Deviation); Unit of measure: %
	Number Analyzed	35 participants	39 participants	74 participants
		7.5 (1.0)	7.6 (1.3)	7.5 (1.1)
Urinary albumin/creatinine; Median (Inter-Quartile Range); Unit of measure: Mg/g
	Number Analyzed	35 participants	39 participants	74 participants
		121; (84 to 412)	131; (46 to 324)	121; (58 to 370)
Urinary pH; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	35 participants	39 participants	74 participants
		5.6 (0.4)	5.4 (0.4)	5.5 (0.4)
Urinary ammonium; Mean (Standard Deviation); Unit of measure: Meq/d
	Number Analyzed	35 participants	39 participants	74 participants
		36 (18)	33 (21)	34 (20)
Urinary titratable acids; Mean (Standard Deviation); Unit of measure: Meq/d
	Number Analyzed	35 participants	39 participants	74 participants
		32 (14)	31 (16)	32 (15)
Urinary transforming growth factor-B1/creatinine; Median (Inter-Quartile Range); Unit of measure: Ng/g
	Number Analyzed	35 participants	39 participants	74 participants
		122; (79 to 186)	103; (68 to 147)	112; (74 to 157)
Urinary kidney injury molecule-1/creatinine; Median (Inter-Quartile Range); Unit of measure: Ng/mg
	Number Analyzed	35 participants	39 participants	74 participants
		0.91; (0.57 to 1.87)	0.88; (0.59 to 1.89)	0.89; (0.58 to 1.87)
Urinary fibronectin/creatinine; Median (Inter-Quartile Range); Unit of measure: Ng/mg
	Number Analyzed	35 participants	39 participants	74 participants
		107; (75 to 194)	97; (65 to 147)	102; (74 to 173)
Urinary neutrophil gelatinase-associated lipocalin/creatinine; Median (Inter-Quartile Range); Unit of measure: Ng/mg
	Number Analyzed	35 participants	39 participants	74 participants
		10.5; (7.0 to 23.6)	11.9; (6.3 to 24.0)	11.1; (6.5 to 23.8)

Outcome Measures

1. Primary Outcome

Title	Change in Urinary Transforming Growth Factor Beta 1 (TGF-b1)
Description	Urinary TGF-b1 is considered a marker of renal fibrosis
Time Frame	The mean of the 3-month and 6-month urinary TGF-b1 measurement will be compared to the baseline value between the groups.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sodium Bicarbonate	Placebo
Arm/Group Description:	Participants were prescribed 0.5 meq of sodium bicarbonate per 1 kilogram of lean body weight daily for six months Sodium bicarbonate: Participants will receive 0.5 meq of sodium bicarbonate per 1 kilogram of lean body weight daily. The total amount will be divided into twice daily doses.	Participants were prescribed an identical number of placebo tablets had they been assigned to the intervention, and took this daily for six months. Placebo: Participants will receive an identical number of placebo tablets had they been assigned to the intervention. Placebo will be divided into twice daily doses and receive this for six months.
Overall Number of Participants Analyzed	35	39
Geometric Mean (95% Confidence Interval); Unit of Measure: percent change
	7.6; (-9.6 to 28.0)	-4.4; (-19.4 to 13.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sodium Bicarbonate, Placebo
	Comments	The primary analysis compared the mean change from baseline in the sodium bicarbonate group to the mean change from baseline in the placebo group.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	12.6
	Confidence Interval	(2-Sided) 95%; -9.6 to 40.1
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Change in Urinary Levels of Kidney Injury Molecule-1 (KIM-1)
Description	KIM-1 is a marker of of kidney injury.
Time Frame	The mean of the 3-month and 6-month measurements will be compared to the baseline values between the groups.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sodium Bicarbonate	Placebo
Arm/Group Description:	Participants were prescribed 0.5 meq of sodium bicarbonate per 1 kilogram of lean body weight daily for six months.	Participants were prescribed an identical number of placebo tablets had they been assigned to the intervention, and took this daily for six months.
Overall Number of Participants Analyzed	35	39
Mean (95% Confidence Interval); Unit of Measure: percent change
	-11.4; (-33.0 to 17.0)	-1.5; (-24.9 to 29.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sodium Bicarbonate, Placebo
	Comments	The main analytic strategy for this secondary outcome was a comparison of the mean change from baseline in the sodium bicarbonate group to the mean change from baseline in the placebo group.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-10.1
	Confidence Interval	(2-Sided) 95%; -38.2 to 30.8
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Change in Urinary Levels of Neutrophil Gelatinase-associated Lipocalin (NGAL)
Description	NGAL is a marker of kidney injury
Time Frame	The mean of the 3-month and 6-month measurements will be compared to the baseline values between the groups.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sodium Bicarbonate	Placebo
Arm/Group Description:	Participants were prescribed 0.5 meq of sodium bicarbonate per 1 kilogram of lean body weight daily for six months Sodium bicarbonate: Participants will receive 0.5 meq of sodium bicarbonate per 1 kilogram of lean body weight daily. The total amount will be divided into twice daily doses.	Participants were prescribed an identical number of placebo tablets had they been assigned to the intervention, and took this daily for six months. Placebo: Participants will receive an identical number of placebo tablets had they been assigned to the intervention. Placebo will be divided into twice daily doses and receive this for six months.
Overall Number of Participants Analyzed	35	39
Geometric Mean (95% Confidence Interval); Unit of Measure: percent change
	-28.5; (-48.7 to -0.3)	5.9; (-23.9 to 47.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sodium Bicarbonate, Placebo
	Comments	The main analytic strategy for this secondary outcome was a comparison of the mean change from baseline in the sodium bicarbonate group to the mean change from baseline in the placebo group.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-32.5
	Confidence Interval	(2-Sided) 95%; -56.3 to 4.2
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Change in Urinary Levels of Fibronectin
Description	Fibronectin is a marker of kidney injury.
Time Frame	The mean of the 3-month and 6-month measurements will be compared to the baseline values between the groups.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sodium Bicarbonate	Placebo
Arm/Group Description:	Participants were prescribed 0.5 meq of sodium bicarbonate per 1 kilogram of lean body weight daily for six months.	Participants were prescribed an identical number of placebo tablets had they been assigned to the intervention, and took this daily for six months.
Overall Number of Participants Analyzed	35	39
Geometric Mean (95% Confidence Interval); Unit of Measure: percent change
	8.8; (-9.4 to 30.7)	1.1; (-15.8 to 21.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sodium Bicarbonate, Placebo
	Comments	The main analytic strategy for this secondary outcome was a comparison of the mean change from baseline in the sodium bicarbonate group to the mean change from baseline in the placebo group.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	7.7
	Confidence Interval	(2-Sided) 95%; -15.1 to 36.5
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Change in Urinary Albumin Levels
Description	Urinary albumin is a marker of kidney damage
Time Frame	The mean of the 3-month and 6-month measurements will be compared to the baseline values between the groups.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sodium Bicarbonate	Placebo
Arm/Group Description:	Sodium bicarbonate: Participants will receive 0.5 meq of sodium bicarbonate per 1 kilogram of lean body weight daily. The total amount will be divided into twice daily doses.	Placebo: Participants will receive an identical number of placebo tablets had they been assigned to the intervention. Placebo will be divided into twice daily doses and receive this for six months.
Overall Number of Participants Analyzed	35	39
Geometric Mean (95% Confidence Interval); Unit of Measure: percent change
	21.1; (-3.1 to 51.3)	11.9; (-10.5 to 39.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sodium Bicarbonate, Placebo
	Comments	The main analytic strategy for this secondary outcome was a comparison of the mean change from baseline in the sodium bicarbonate group to the mean change from baseline in the placebo group.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95%; -24.6 to 35.9
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Change in Estimated Glomerular Filtration (eGFR)
Description	eGFR is a measure of kidney function
Time Frame	The mean of the 3-month and 6-month measurements will be compared to the baseline values between the groups.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sodium Bicarbonate	Placebo
Arm/Group Description:	Sodium bicarbonate: Participants will receive 0.5 meq of sodium bicarbonate per 1 kilogram of lean body weight daily. The total amount will be divided into twice daily doses.	Placebo: Participants will receive an identical number of placebo tablets had they been assigned to the intervention. Placebo will be divided into twice daily doses and receive this for six months.
Overall Number of Participants Analyzed	35	39
Mean (95% Confidence Interval); Unit of Measure: ml/min per 1.73m2
	1.96; (-0.47 to 4.40)	-1.41; (-3.80 to 0.99)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sodium Bicarbonate, Placebo
	Comments	The main analytic strategy for this secondary outcome was a comparison of the mean change from baseline in the sodium bicarbonate group to the mean change from baseline in the placebo group.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.37
	Confidence Interval	(2-Sided) 95%; -0.05 to 6.79
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Adverse event data were collected during each participant's 6-month follow-up period.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Sodium Bicarbonate	Placebo
Arm/Group Description	Sodium bicarbonate: Participants will receive 0.5 meq of sodium bicarbonate per 1 kilogram of lean body weight daily. The total amount will be divided into twice daily doses.	Placebo: Participants will receive an identical number of placebo tablets had they been assigned to the intervention. Placebo will be divided into twice daily doses and receive this for six months.
All-Cause Mortality
	Sodium Bicarbonate	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/35 (0.00%)	0/39 (0.00%)
Serious Adverse Events
	Sodium Bicarbonate	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/35 (0.00%)	0/39 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Sodium Bicarbonate	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/35 (0.00%)	0/39 (0.00%)

Limitations and Caveats

Change in urinary levels of Bb and membrane attack complex (MAC) were initial secondary outcomes. However, we had difficulty measuring these. Many subjects could not complete the physical activity assessment, which was an initial secondary outcome.

More Information

Certain Agreements

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

Results Point of Contact

• Name/Title: Dr. Kalani Raphael, Principal Investigator
• Organization: VA Salt Lake City Healthcare System
• Phone: 801-582-1565 ext 1794
• EMail: kalani.raphael@va.gov

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT01574157
• Other Study ID Numbers: CLIN-002-11F
• First Submitted: March 27, 2012
• First Posted: April 10, 2012
• Results First Submitted: June 26, 2019
• Results First Posted: August 28, 2019
• Last Update Posted: August 28, 2019