Chronic Kidney Disease
Conditions
Brief summary
The two doses of sodium bicarbonate being tested are 0.5 and 0.8 mEq/kg-lean body weight (LBW) per day. Sodium bicarbonate, also known as baking soda, may help prevent kidney failure in people with chronic kidney disease. However, the dose to prescribe in order to test this possibility in a clinical trial is uncertain. The BASE pilot clinical trial will help determine the best dose of sodium bicarbonate to prescribe in a future study that will test the long-term safety and efficacy of sodium bicarbonate as a treatment to preserve kidney function in individuals with chronic kidney disease.
Interventions
DRUGLower Dose Sodium Bicarbonate
Lower dose oral Sodium Bicarbonate (0.5 milliequivalents (mEq)/kg-LBW/day)
DRUGHigher Dose Sodium Bicarbonate
Higher dose oral Sodium Bicarbonate (0.8 mEq/kg-LBW/day)
DRUGPlacebo
Oral placebo equivalent to either 0.5 mEq/kg-LBW/day or 0.8 mEq/kg-LBW/day of Sodium Bicarbonate
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
The Cleveland Clinic
Jennifer Gassman, PhD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Serum bicarbonate 20-28 mEq/L at screening (the average of the two most recent values in Baseline must be 20-28 mEq/L prior to randomization) 2. Moderate to severe chronic kidney disease (CKD) at the time of screening, defined as one of the following: * eGFR 20-44 ml/min/1.73m2 or * eGFR 45-59 ml/min/1.73m2 plus random urinary albumin:creatinine (ACR) ≥100 mg/gm 3. Blood pressure \<160/100 mm Hg at screening (must be \<150/100 mm Hg prior to randomization) 4. Lean body weight 38.0-96.0 kg at the time of screening 5. Age allowing legal consent without parental involvement (18-21 years, depending on individual state regulations) 6. Able to provide consent 7. Able to travel to study visits 8. Able to read English 9. In the opinion of the site investigator, willing and able to follow the study treatment regimen and comply with the site investigator's recommendations 10. In the opinion of the site investigator, medically stable
Exclusion criteria
1. Use of chronic daily oral alkali (such as sodium bicarbonate, sodium citrate, potassium citrate, etc) with one exception: calcium carbonate ≤1500 mg/day is allowed, as some will take this for the indication of bone health 2. On five or more antihypertensive and/or diuretic agents, regardless of the indication 3. Serum potassium \<3.3 or ≥5.5 mEq/L at screening (must be 3.5-5.5 mEq/L prior to randomization) 4. Self-reported vegetarian 5. New York Heart Association Class 3 or 4 heart failure symptoms, known left ventricular ejection fraction ≤30%, or hospital admission for heart failure within the past 3 months 6. Frequent urinary tract infections (≥2 in the past year) 7. Presence of indwelling urinary catheter or urinary conduit (such as neobladder or urostomy) 8. Factors judged to limit adherence to interventions (e.g., alcoholism, history of missing clinic visits, chronic gastrointestinal disorder that makes compliance with the intervention unreliable) 9. Organ transplant recipients (excluding cornea) 10. Active glomerular disease requiring or potentially requiring immunosuppressive treatment 11. Chronic immunosuppressive therapy (for ≥3 months) for any indication. This does not include oral steroids \<10 mg per day, inhaled steroids, or topical steroids 12. Anticipated initiation of dialysis or kidney transplantation within 12 months as assessed by the site investigator 13. Current participation in another interventional research study 14. Malignancy requiring therapy within 2 years (basal or squamous cell skin carcinoma and localized prostate cancer are exempted) 15. Pregnancy or planning to become pregnant or currently breast-feeding. Women of childbearing potential (pre-menopausal and not surgically sterilized) will have urine pregnancy test before enrollment. 16. Life expectancy \<12 months as determined by the site investigator 17. Institutionalized individuals, including prisoners and nursing home residents 18. Plans to leave the immediate area within the next 12 months 19. Routinely leaves town for multiple weeks each year such that protocol visits would be missed 20. Chronic use of supplemental oxygen 21. Use of both angiotensin-converting-enzyme inhibitor (ACEI) and Angiotensin II Receptor Blockers (ARBs)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants in Each Dose Arm Prescribed (i) Full Randomized Sodium Bicarbonate Dose at End of 28 Weeks & (ii) at Least 25% of Randomized Sodium Bicarbonate Dose at End of 28 Weeks as a Proportion of the Number Randomized to That Group | Baseline, 28 weeks | The prescribed dose for each participant at the end of 28 weeks will be determined by the safety and tolerability of each dose during the intervention period. The primary assessments will examine the percentage of participants in each dose arm who are prescribed (i) the full randomized sodium bicarbonate dose according to the protocol at the end of 28 weeks and (ii) at least 25% of the randomized sodium bicarbonate dose according to the protocol at the end of 28 weeks. The two doses of sodium bicarbonate being tested are 0.5 and 0.8 mEq/kg-lean body weight per day. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from the CKD medical clinic patients of the recruiting centers.
Participants by arm
| Arm | Count |
|---|---|
| Lower Dose Sodium Bicarbonate Participants will receive oral 0.5 milliequivalents (mEq)/kg-lean body weight (LBW)/day of sodium bicarbonate. Half of the total daily dose is taken in the morning and the other half is taken in the evening. (If the number of capsules is an odd number, the greater number of capsules will be taken in the morning.)
Lower Dose Sodium Bicarbonate: Lower dose oral Sodium Bicarbonate (0.5 milliequivalents (mEq)/kg-LBW/day) | 52 |
| Higher Dose Sodium Bicarbonate Participants will receive 0.8 mEq/kg-LBW/day of sodium bicarbonate. Half the total daily dose is taken in the morning and the other half is taken in the evening. (If the number of capsules is an odd number, the greater number of capsules will be taken in the morning.)
Higher Dose Sodium Bicarbonate: Higher dose oral Sodium Bicarbonate (0.8 mEq/kg-LBW/day) | 90 |
| Placebo Participants will take the same number of placebo capsules as if they were assigned to receive either 0.5 mEq/kg-LBW/day or 0.8 mEq/kg-LBW/day of sodium bicarbonate. Half the total daily dose is taken in the morning and the other half is taken in the evening. (If the number of capsules is an odd number, the greater number of capsules will be taken in the morning.)
Placebo: Oral placebo equivalent to either 0.5 mEq/kg-LBW/day or 0.8 mEq/kg-LBW/day of Sodium Bicarbonate | 52 |
| Total | 194 |
Baseline characteristics
| Characteristic | Higher Dose Sodium Bicarbonate | Lower Dose Sodium Bicarbonate | Placebo | Total |
|---|---|---|---|---|
| Ace/ARB Use | 60 Participants | 40 Participants | 35 Participants | 135 Participants |
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 51 Participants | 32 Participants | 37 Participants | 120 Participants |
| Age, Categorical Between 18 and 65 years | 39 Participants | 20 Participants | 15 Participants | 74 Participants |
| Age, Continuous | 67.3 years STANDARD_DEVIATION 10.8 | 65.9 years STANDARD_DEVIATION 14 | 66.2 years STANDARD_DEVIATION 10.8 | 66.6 years STANDARD_DEVIATION 11.7 |
| BMI | 32.8 kg/m^2 STANDARD_DEVIATION 7.87 | 32.8 kg/m^2 STANDARD_DEVIATION 8.43 | 31.6 kg/m^2 STANDARD_DEVIATION 5.92 | 32.5 kg/m^2 STANDARD_DEVIATION 7.54 |
| CKD Stage Stage 3A (eGFR 45-60) | 17 Participants | 9 Participants | 4 Participants | 30 Participants |
| CKD Stage Stage 3B (eGFR 30-45) | 46 Participants | 30 Participants | 31 Participants | 107 Participants |
| CKD Stage Stage 4 (eGFR 15-30) | 27 Participants | 13 Participants | 17 Participants | 57 Participants |
| Congestive Heart Failure | 8 Participants | 5 Participants | 7 Participants | 20 Participants |
| COPD | 6 Participants | 4 Participants | 0 Participants | 10 Participants |
| Diabetes Mellitus | 53 Participants | 27 Participants | 25 Participants | 105 Participants |
| eGFR | 36.4 ml/min/1.73m^2 STANDARD_DEVIATION 9.6 | 36.5 ml/min/1.73m^2 STANDARD_DEVIATION 9.56 | 34.5 ml/min/1.73m^2 STANDARD_DEVIATION 8.59 | 35.9 ml/min/1.73m^2 STANDARD_DEVIATION 9.32 |
| Estimated DIetary Protein Intake | 81.9 g/day STANDARD_DEVIATION 30.5 | 73.3 g/day STANDARD_DEVIATION 25.4 | 79.1 g/day STANDARD_DEVIATION 29.5 | 78.8 g/day STANDARD_DEVIATION 29 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 6 Participants | 3 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 82 Participants | 46 Participants | 49 Participants | 177 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| History of Heart Disease | 28 Participants | 18 Participants | 20 Participants | 66 Participants |
| Lean Body Mass | 58.4 kg STANDARD_DEVIATION 9.84 | 58.4 kg STANDARD_DEVIATION 10.7 | 58.7 kg STANDARD_DEVIATION 9.44 | 58.5 kg STANDARD_DEVIATION 9.91 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 3 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 27 Participants | 17 Participants | 23 Participants | 67 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) White | 55 Participants | 28 Participants | 26 Participants | 109 Participants |
| Region of Enrollment United States | 90 participants | 52 participants | 52 participants | 194 participants |
| Serum Bicarbonate | 24.2 meq/L STANDARD_DEVIATION 2.38 | 24.2 meq/L STANDARD_DEVIATION 2.25 | 23.8 meq/L STANDARD_DEVIATION 2.17 | 24.1 meq/L STANDARD_DEVIATION 2.28 |
| Serum Potassium | 4.4 meq/L STANDARD_DEVIATION 0.4 | 4.5 meq/L STANDARD_DEVIATION 0.4 | 4.5 meq/L STANDARD_DEVIATION 0.5 | 4.5 meq/L STANDARD_DEVIATION 0.4 |
| Sex: Female, Male Female | 29 Participants | 21 Participants | 13 Participants | 63 Participants |
| Sex: Female, Male Male | 61 Participants | 31 Participants | 39 Participants | 131 Participants |
| Smoking Status Current Smoker | 4 Participants | 11 Participants | 2 Participants | 17 Participants |
| Smoking Status Former Smoker | 39 Participants | 15 Participants | 25 Participants | 79 Participants |
| Smoking Status Never | 47 Participants | 26 Participants | 25 Participants | 98 Participants |
| Systolic BP | 127 mm Hg STANDARD_DEVIATION 12.3 | 127 mm Hg STANDARD_DEVIATION 13.7 | 127 mm Hg STANDARD_DEVIATION 13 | 127 mm Hg STANDARD_DEVIATION 12.8 |
| Urinary Ammonium | 22.0 mmol/day STANDARD_DEVIATION 12.2 | 19.3 mmol/day STANDARD_DEVIATION 10.5 | 20.5 mmol/day STANDARD_DEVIATION 13.2 | 20.9 mmol/day STANDARD_DEVIATION 12 |
| Urinary PH | 5.75 units on a scale STANDARD_DEVIATION 0.46 | 5.86 units on a scale STANDARD_DEVIATION 0.46 | 5.81 units on a scale STANDARD_DEVIATION 0.56 | 5.80 units on a scale STANDARD_DEVIATION 0.49 |
| Urine Albumin / Creatinine Ratio | 176 g/mg | 222 g/mg | 147 g/mg | 181 g/mg |
| Weight | 95.4 kg STANDARD_DEVIATION 22.4 | 96.1 kg STANDARD_DEVIATION 25.8 | 93.6 kg STANDARD_DEVIATION 20.3 | 95.1 kg STANDARD_DEVIATION 22.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 52 | 0 / 90 | 1 / 52 |
| other Total, other adverse events | 40 / 52 | 74 / 90 | 42 / 52 |
| serious Total, serious adverse events | 5 / 52 | 16 / 90 | 7 / 52 |
Outcome results
Primary
Number of Participants in Each Dose Arm Prescribed (i) Full Randomized Sodium Bicarbonate Dose at End of 28 Weeks & (ii) at Least 25% of Randomized Sodium Bicarbonate Dose at End of 28 Weeks as a Proportion of the Number Randomized to That Group
The prescribed dose for each participant at the end of 28 weeks will be determined by the safety and tolerability of each dose during the intervention period. The primary assessments will examine the percentage of participants in each dose arm who are prescribed (i) the full randomized sodium bicarbonate dose according to the protocol at the end of 28 weeks and (ii) at least 25% of the randomized sodium bicarbonate dose according to the protocol at the end of 28 weeks. The two doses of sodium bicarbonate being tested are 0.5 and 0.8 mEq/kg-lean body weight per day.
Time frame: Baseline, 28 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lower Dose Sodium Bicarbonate | Number of Participants in Each Dose Arm Prescribed (i) Full Randomized Sodium Bicarbonate Dose at End of 28 Weeks & (ii) at Least 25% of Randomized Sodium Bicarbonate Dose at End of 28 Weeks as a Proportion of the Number Randomized to That Group | Number of Patients Completing on Full Dose | 50 participants |
| Lower Dose Sodium Bicarbonate | Number of Participants in Each Dose Arm Prescribed (i) Full Randomized Sodium Bicarbonate Dose at End of 28 Weeks & (ii) at Least 25% of Randomized Sodium Bicarbonate Dose at End of 28 Weeks as a Proportion of the Number Randomized to That Group | Num of Patients Completing on >= 25% of Full Dose | 51 participants |
| Higher Dose Sodium Bicarbonate | Number of Participants in Each Dose Arm Prescribed (i) Full Randomized Sodium Bicarbonate Dose at End of 28 Weeks & (ii) at Least 25% of Randomized Sodium Bicarbonate Dose at End of 28 Weeks as a Proportion of the Number Randomized to That Group | Number of Patients Completing on Full Dose | 78 participants |
| Higher Dose Sodium Bicarbonate | Number of Participants in Each Dose Arm Prescribed (i) Full Randomized Sodium Bicarbonate Dose at End of 28 Weeks & (ii) at Least 25% of Randomized Sodium Bicarbonate Dose at End of 28 Weeks as a Proportion of the Number Randomized to That Group | Num of Patients Completing on >= 25% of Full Dose | 82 participants |
| Placebo | Number of Participants in Each Dose Arm Prescribed (i) Full Randomized Sodium Bicarbonate Dose at End of 28 Weeks & (ii) at Least 25% of Randomized Sodium Bicarbonate Dose at End of 28 Weeks as a Proportion of the Number Randomized to That Group | Number of Patients Completing on Full Dose | 45 participants |
| Placebo | Number of Participants in Each Dose Arm Prescribed (i) Full Randomized Sodium Bicarbonate Dose at End of 28 Weeks & (ii) at Least 25% of Randomized Sodium Bicarbonate Dose at End of 28 Weeks as a Proportion of the Number Randomized to That Group | Num of Patients Completing on >= 25% of Full Dose | 48 participants |