Variable Dialysate Bicarbonate for Cardiac Dysrhythmias

Overseen By Katherine S Ravi, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Brigham and Women's Hospital

Disqualifiers: Anemia, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: Up to 2 weeks

141 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Dialysate Bicarbonate Concentration for Cardiac Dysrhythmias?

Research suggests that using bicarbonate in hemodialysis can help maintain the body's acid-base balance, which is important for overall health. Additionally, bicarbonate may reduce symptoms like dizziness when standing up after dialysis, especially when used with lower sodium levels. ^{1 2 3 4 5}

Is variable dialysate bicarbonate safe for use in humans?

Research shows that using bicarbonate in dialysis is generally safe, but there can be side effects like fatigue and muscle cramps if the pH is too low. Long-term use of sodium bicarbonate in dialysis has been found safe in some studies, and it may help reduce certain symptoms compared to other solutions. ^{2 6 7 8 9}

How is the treatment of variable dialysate bicarbonate for cardiac dysrhythmias different from other treatments?

This treatment is unique because it involves adjusting the concentration of bicarbonate in the dialysis fluid, which can help correct acid-base imbalances more effectively than traditional dialysis methods. It also allows for point-of-care adjustments based on individual patient needs, potentially reducing the risk of arrhythmias (irregular heartbeats) by managing potassium and acid levels more precisely. ^{2 3 4 10 11}

What is the purpose of this trial?

QTc prolongation and premature ventricular contractions (PVCs) are common in hemodialysis (HD) patients and are associated with sudden cardiac death. It is known that higher dialysate bicarbonate is associated with more QTc prolongation during HD sessions. This study aims to assess the effects of lower (30 mEq/L) versus higher (35 mEq/L) dialysate bicarbonate in adult maintenance HD patients admitted to the hospital. The investigators will randomly assign subjects to lower versus higher dialysate bicarbonate concentrations during their hospital stay for up to a maximum of six HD sessions or until their hospital discharge.

Research Team

Katherine S Ravi, MD, MPH

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

This trial is for adults over 18 with end-stage renal disease who have been on maintenance hemodialysis (HD) for more than 90 days, receiving treatments three times a week. It's not specified who can't join the trial.

Inclusion Criteria

I undergo hemodialysis three times a week.

I have been on dialysis for over 90 days due to kidney failure.

Exclusion Criteria

Hemoglobin less than 8.0 g/dL

Any physical, mental, or medical condition which limits the ability to provide written informed consent

Pregnancy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either lower (30 mEq/L) or higher (35 mEq/L) dialysate bicarbonate during their hospital stay for up to six hemodialysis sessions or until discharge

Up to 2 weeks

Up to 6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of blood pressure, arrhythmias, and adverse symptoms

1-2 weeks

Treatment Details

Interventions

• Dialysate Bicarbonate Concentration
• Dialysate Bicarbonate Concentration - Telemetry Monitoring

Trial Overview The study tests the effects of two different bicarbonate levels in dialysate during HD sessions: lower (30 mEq/L) and higher (35 mEq/L). Patients are randomly assigned to one of these conditions during their hospital stay, up to six HD sessions or until discharge.

Participant Groups

Group I: Lower dialysate bicarbonate Experimental Treatment 2 Interventions

A lower dialysate bicarbonate will be used in the experimental arm (30 mEq/L).

Group II: Higher dialysate bicarbonate Active Control 2 Interventions

A higher dialysate bicarbonate will be used in the active comparator arm (35 mEq/L).

Dialysate Bicarbonate Concentration is already approved in United States, European Union, Canada, Japan, China for the following indications:

Approved in United States as Sodium Bicarbonate Solution for:

• Acidosis correction in hemodialysis patients

Approved in European Union as Bicarbonate Dialysate for:

• Electrolyte imbalance correction in renal failure patients undergoing hemodialysis

Approved in Canada as Sodium Bicarbonate Solution for:

• Metabolic acidosis treatment in patients on hemodialysis

Approved in Japan as Bicarbonate Dialysate for:

• Hemodialysis fluid for correcting acid-base balance

Approved in China as Sodium Bicarbonate Solution for:

• Correction of metabolic acidosis in patients undergoing hemodialysis

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Findings from Research

In a study of 313 hemodialysis patients, a dialysate bicarbonate concentration (DBIC) of 31-32 mmol/L was associated with the lowest mortality rate, suggesting this range may optimize patient outcomes.

Higher DBIC levels (≥33.6 mmol/L) were linked to significantly increased all-cause mortality, with a hazard ratio of 4.29 for every 3 mmol/L increase, indicating that excessively high bicarbonate levels could be harmful.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship between dialysate bicarbonate concentration and all-cause mortality in hemodialysis patients. Wan, J., Lin, J., Wang, W., et al.[2023]

In a study involving 12 stable hemodialysis patients, bicarbonate dialysate did not show greater hemodynamic stability compared to acetate when using high-sodium dialysate (141 mEq/liter).

However, under low-sodium dialysate conditions (130 mEq/liter), bicarbonate significantly reduced adverse symptoms upon standing in patients with normal autonomic function and prevented a drop in blood pressure in those with autonomic insufficiency, indicating a potential benefit of bicarbonate in specific conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acetate and bicarbonate hemodialysis in patients with and without autonomic dysfunction. Velez, RL., Woodard, TD., Henrich, WL.[2019]

In a study of 17,031 hemodialysis patients, higher dialysate bicarbonate concentrations (≥38 mEq/L) were associated with increased mortality, suggesting that excessive bicarbonate may lead to adverse outcomes.

The risk of mortality was particularly pronounced in patients with longer dialysis histories, indicating that prolonged exposure to high bicarbonate levels could contribute to complications like metabolic alkalosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of dialysate bicarbonate concentration with mortality in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Tentori, F., Karaboyas, A., Robinson, BM., et al.[2022]

A pilot study involving 19 participants demonstrated that point-of-care (POC) testing for potassium and bicarbonate adjustments in hemodialysis is feasible, with 85% adherence to the intervention protocols.

While there were no serious adverse events, the study noted a high variability in potassium and bicarbonate levels between treatments, suggesting that a POC-guided approach could significantly improve the management of dialysate chemistry and potentially reduce the risk of clinically significant arrhythmias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Point-of-Care Chemistry-Guided Dialysate Adjustment to Reduce Arrhythmias: A Pilot Trial. Pun, PH., Santacatterina, M., Ways, J., et al.[2023]

Chronic metabolic acidosis is a common issue in dialysis patients, and maintaining serum bicarbonate levels through dialysate is crucial for acid-base balance, but the ideal serum bicarbonate level remains unclear due to various influencing factors.

Recent observational studies suggest that both very low and very high serum bicarbonate levels can lead to adverse outcomes, but when accounting for nutritional status, higher predialysis serum bicarbonate does not appear to be linked to negative consequences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pro: Higher serum bicarbonate in dialysis patients is protective. Misra, M.[2022]

In a study analyzing six commercially available bicarbonate-containing dialysates, it was found that low pH and high pCO2 levels can lead to side effects.

Two of the dialysates were specifically linked to adverse effects such as fatigue, muscle cramps, and somnolence, highlighting the importance of monitoring dialysate composition for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side effects in bicarbonate dialysis due to low dialysate pH. Wagner, L., Schindler, B., Marhoffer, W., et al.[2013]

In a study involving 12 patients undergoing hemodialysis for 2 weeks, using sodium bicarbonate to increase sodium levels in dialysate resulted in lower intradialytic morbidity and less hypoxemia compared to using sodium chloride.

The long-term use of sodium bicarbonate-added dialysate was found to be safe in three patients, suggesting it may be a preferable option for certain patients without the need for pH adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increment in dialysate sodium with sodium chloride or bicarbonate addition. Raja, RM., Fernandes, M., Kramer, MS., et al.[2019]

Calcium carbonate can precipitate in dialysate delivery systems that use bicarbonate-containing solutions, potentially causing blockages and system failures.

Contamination of commercial sodium bicarbonate supplies with sodium carbonate leads to immediate calcium carbonate precipitation; however, sparging the bicarbonate concentrate with carbon dioxide can prevent this issue by converting carbonate to bicarbonate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calcium carbonate precipitation in bicarbonate hemodialysis. Klein, E., Ward, RA., Harding, GB.[2019]

A study involving 39 hemodialysis patients showed that using higher concentrations of NaturaLyte bicarbonate dialysate leads to significant increases in serum bicarbonate levels immediately after dialysis and 2 hours post-dialysis, indicating rapid fluctuations in acid-base balance.

The findings suggest that correcting pre-dialysis acidosis with high bicarbonate dialysate may not be necessary, as bicarbonate levels return to baseline within 44 to 68 hours, potentially reducing the risk of metabolic alkalosis and associated complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in Serum Bicarbonate Levels Caused by Acetate-Containing Bicarbonate-Buffered Hemodialysis Solution: An Observational Prospective Cohort Study. Panesar, M., Shah, N., Vaqar, S., et al.[2017]

The new method for preparing a stable bicarbonate dialysate was tested on 4 patients over periods of 4 months to 1 year, showing excellent clinical tolerance even with high dehydration rates during dialysis sessions.

Bicarbonate dialysis significantly improved acid-base balance compared to traditional dialysis methods, leading to better correction of acidosis and normalization of potassium levels without causing significant changes in blood gas levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term use of a "stable" bicarbonate containing dialysate. Bigi, L., Orlandini, GC., Cappelli, G., et al.[2019]

In a study involving 200 blood samples from hemodialysis sessions, it was found that higher levels of bicarbonate in the dialysate and lower sodium levels were linked to increased blood pH after treatment.

The results suggest that adjusting the dialysate bicarbonate based on pre-hemodialysis serum bicarbonate levels is unnecessary, as the relationship between them was only modest, indicating that other factors may influence blood pH during dialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of dialysate bicarbonate and sodium on blood pH in maintenance hemodialysis-A prospective study. Sridhar, NR., Chen, Z., Yu, G., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Relationship between dialysate bicarbonate concentration and all-cause mortality in hemodialysis patients. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Acetate and bicarbonate hemodialysis in patients with and without autonomic dysfunction. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Association of dialysate bicarbonate concentration with mortality in the Dialysis Outcomes and Practice Patterns Study (DOPPS). [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Point-of-Care Chemistry-Guided Dialysate Adjustment to Reduce Arrhythmias: A Pilot Trial. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Pro: Higher serum bicarbonate in dialysis patients is protective. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Side effects in bicarbonate dialysis due to low dialysate pH. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Increment in dialysate sodium with sodium chloride or bicarbonate addition. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Calcium carbonate precipitation in bicarbonate hemodialysis. [2019]

9. Australia pubmed.ncbi.nlm.nih.gov

Changes in Serum Bicarbonate Levels Caused by Acetate-Containing Bicarbonate-Buffered Hemodialysis Solution: An Observational Prospective Cohort Study. [2017]

10. United States pubmed.ncbi.nlm.nih.gov

Long-term use of a "stable" bicarbonate containing dialysate. [2019]

11. Australia pubmed.ncbi.nlm.nih.gov

Effect of dialysate bicarbonate and sodium on blood pH in maintenance hemodialysis-A prospective study. [2023]