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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different levels of dialysate bicarbonate (a substance that helps balance acid in the blood) affect heart rhythm issues in people undergoing hemodialysis (a treatment that filters waste from the blood). Specifically, it aims to reduce a heart rhythm problem called QTc prolongation, which can increase the risk of sudden heart problems. Participants will receive either a lower or higher concentration of dialysate bicarbonate during their hospital stay. Individuals who have been on hemodialysis for more than 90 days and undergo it three times a week might be suitable for this study. As an unphased trial, this study offers a unique opportunity to contribute to important research that could improve heart health for dialysis patients.

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 prior data suggests that this protocol is safe for hemodialysis patients?

Research has shown that varying the amounts of dialysate bicarbonate, a solution used in dialysis, can affect heart health in individuals undergoing hemodialysis. Studies have found that higher levels of this solution link to an increased risk of heart rhythm issues, such as QTc prolongation and premature ventricular contractions (PVCs), which can potentially lead to sudden cardiac death.

One study found that altering bicarbonate levels in the solution did not cause serious side effects. However, higher bicarbonate levels are known to increase the risk of heart-related problems. Evidence suggests that adjusting the bicarbonate concentration might be safe, but monitoring any changes in heart health is crucial.

Overall, this treatment appears generally well-tolerated, but vigilance for heart-related side effects is important. Participants in this trial should feel comfortable discussing any concerns with the study team. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how different concentrations of dialysate bicarbonate might affect cardiac dysrhythmias in patients undergoing dialysis. Unlike the standard practice, which typically uses a fixed bicarbonate level, this trial investigates the effects of both higher (35 mEq/L) and lower (30 mEq/L) bicarbonate concentrations. By adjusting bicarbonate levels, the trial seeks to uncover whether these variations can better manage or reduce heart rhythm issues, potentially offering a more tailored approach to patient care.

What evidence suggests that this trial's treatments could be effective for cardiac dysrhythmias?

This trial will compare different dialysate bicarbonate concentrations to assess their impact on cardiac dysrhythmias in patients undergoing hemodialysis. Studies have shown that higher bicarbonate levels in dialysis fluid can increase the risk of heart rhythm problems. In this trial, participants in the active comparator arm will receive a higher dialysate bicarbonate concentration (35 mEq/L), while those in the experimental arm will receive a lower concentration (30 mEq/L). Research suggests that a lower bicarbonate level might reduce the risk of irregular heartbeats. The main goal is to find a balance that prevents excessive acidity in the body without causing heart issues. Adjusting bicarbonate levels during dialysis may reduce these risks and improve patient safety. ^{2 3 4 6 7}

Who Is on the Research Team?

Katherine S Ravi, MD, MPH

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8204783/

Optimization of dialysate bicarbonate in patients treated ... This study analysed the impact of reducing dialysate bicarbonate from 35 to 32 mEq/L on plasma bicarbonate levels in a cohort of patients treated with online ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2468024923014286

Point-of-Care Chemistry-Guided Dialysate Adjustment to ... Nineteen subjects were enrolled in the study. HD staff completed POC testing and correctly adjusted the dialysate in 604 of 708 (85%) of available HD treatments ...

3. researchgate.net researchgate.net/publication/396785894_3163_Dialysate_bicarbonate_concentration_is_associated_with_an_increased_risk_of_cardiac_arrhythmias_in_individuals_receiving_haemodialysis_results_from_a_Danish_multicentre_cohort_study_the_CADDY_stu

#3163 Dialysate bicarbonate concentration is associated ... #3163 Dialysate bicarbonate concentration is associated with an increased risk of cardiac arrhythmias in individuals receiving haemodialysis: ...

4. karger.com karger.com/ajn/article/49/1/74/41567/Effect-of-Bicarbonate-Buffered-Dialysate-on

Effect of Bicarbonate-Buffered Dialysate on Ventricular ... In this study, the mean post-HD serum bicarbonate level increased to 26.7 mEq/L from 21.3 mEq/L pre-HD in association with dialysate ...

5. academic.oup.com academic.oup.com/ckj/article/18/4/sfaf072/8063571

10 tips on how to manage severe arrhythmia in haemodialysis ... High-bicarbonate dialysate: increases potassium uptake by cells, accelerating the initial decline in serum potassium, although the total amount ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3832240/

Association of Dialysate Bicarbonate Concentration With ... Dialysate bicarbonate concentration was positively associated with mortality (adjusted HR, 1.08 per 4 mEq/L higher [95% CI, 1.01–1.15]; HR for dialysate ...

7. kidney-international.org kidney-international.org/article/S0085-2538(16)00278-7/fulltext

The choice of dialysate bicarbonate: do different ... Our review is focused on the potential effects of different dialysate bicarbonate concentrations on hard outcomes such as mortality.