Diuretic Tuner App for Chronic Kidney Disease

Overseen By Kamalanathan K Sambandam, M.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Texas Southwestern Medical Center

Must be taking: Diuretics

Disqualifiers: Dialysis, Dementia, Pregnancy, others

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 90 days

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This purpose of this study is to determine the effectiveness of a mobile phone application in helping to control body swelling in patients with kidney problems. The application will help in the day to day adjustments in diuretic medication dosing. Participants in this study will have an application loaded on to their mobile phone by the study team and be taught how to use it over a 2 hour visit. Participants will need to check their blood pressure and weight daily and enter this information into the mobile phone application every day. Participants will need to follow daily instructions in their medication dosing provided by the application. There will be periodic blood testing. This will happen at 2 weeks, 90 days, and up to 4 other times if necessary. At the end of the study there is a 2 hour study visit during which participants will answer a survey. The total length of the study is 90 days.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you will need to follow daily instructions for diuretic medication dosing provided by the mobile app.

What data supports the effectiveness of the Diuretic Tuner App for Chronic Kidney Disease?

Loop diuretics, which are part of the treatment, are effective in increasing urine output and controlling blood pressure in patients with chronic kidney disease, especially when combined with other diuretics. They are commonly used to manage fluid overload and hypertension in these patients. ^{1 2 3 4 5}

Is the Diuretic Tuner App safe for people with chronic kidney disease?

Thiazide and loop diuretics, which are part of the Diuretic Tuner App, have been used for over 60 years and are generally safe, but they can cause side effects like low sodium or potassium levels, especially in people with advanced kidney disease. ^{3 6 7 8 9}

How is the Diuretic Tuner drug unique for treating chronic kidney disease?

The Diuretic Tuner app combines different types of diuretics (water pills) like loop, thiazide, and potassium-sparing diuretics, which can be tailored to individual needs, potentially offering a more personalized approach to managing fluid balance and blood pressure in chronic kidney disease patients compared to standard treatments. ^{3 4 8 10 11}

Eligibility Criteria

This trial is for adults with severe kidney disease or nephrotic syndrome who have swelling due to fluid overload. They must be able to use a smartphone app, weigh between 100-300 lbs, and not be at immediate risk of needing dialysis or have life-threatening low potassium or sodium levels.

Inclusion Criteria

I have severe kidney issues with swelling in my body and weigh less without the swelling.

Exclusion Criteria

Your blood test shows low levels of potassium.

You are expected to live for less than 6 months.

The presence of a medical condition that would interfere with effectively using the Diuretic Tuner (dementia, illiteracy, or blindness)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants use the Diuretic Tuner mobile application to adjust diuretic dosing based on daily weight and blood pressure inputs

90 days

1 initial visit (in-person), periodic blood testing at 2 weeks, 90 days, and up to 4 other times

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a survey on tool usability

4 weeks

1 visit (in-person) for survey completion

Treatment Details

Interventions

• Diuretic Tuner

Trial Overview The study tests a mobile app called Diuretic Tuner that guides daily diuretic dosing based on the patient's blood pressure and weight inputs. The goal is to manage body swelling in patients over a 90-day period with regular monitoring and final feedback via survey.

Participant Groups

Group I: Diuretic Tuner users Experimental Treatment 1 Intervention

The Diuretic Tuner is a mobile device application that integrates a patient's estimated dry weight and starting diuretic dose (both defined by a healthcare provider) with daily weights and blood pressures to provide individualized guidance to the patient in day-to-day adjustments to his or her diuretic regimen. In addition, the application generates a diary of daily weights, blood pressures, fluid intake, and medication compliance.

Diuretic Tuner is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Diuretics for:

• High Blood Pressure
• Edema
• Heart Failure
• Chronic Kidney Disease
• Liver Disease

Approved in United States as Diuretics for:

• High Blood Pressure
• Edema
• Heart Failure
• Chronic Kidney Disease
• Liver Disease

Approved in Canada as Diuretics for:

• High Blood Pressure
• Edema
• Heart Failure
• Chronic Kidney Disease
• Liver Disease

Approved in Japan as Diuretics for:

• High Blood Pressure
• Edema
• Heart Failure
• Chronic Kidney Disease
• Liver Disease

Approved in China as Diuretics for:

• High Blood Pressure
• Edema
• Heart Failure
• Chronic Kidney Disease
• Liver Disease

Approved in Switzerland as Diuretics for:

• High Blood Pressure
• Edema
• Heart Failure
• Chronic Kidney Disease
• Liver Disease

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Findings from Research

In a study of 33 patients with severe congestive cardiac failure, a fixed 3-day course of a combination of thiazide and loop diuretics was found to be as effective as longer treatment durations in managing the condition.

Both thiazide diuretics, bendrofluazide and metolazone, were equally effective in promoting weight loss due to fluid removal, but bendrofluazide resulted in fewer electrolyte disturbances, suggesting it may be a safer option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination diuretic treatment in severe heart failure: a randomised controlled trial. Channer, KS., McLean, KA., Lawson-Matthew, P., et al.[2019]

Diuretics have transformed the treatment of various conditions, turning once fatal diseases into manageable ones, particularly in cases of salt and water overload and edema.

Different types of diuretics are used for specific conditions: thiazide diuretics for hypertension, loop diuretics for edema and heart failure, and potassium-sparing diuretics for preventing low potassium levels, highlighting their versatility and importance in modern medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Edema and principles of diuretic use. Morrison, RT.[2019]

Chlorthalidone has been shown to effectively reduce blood pressure in patients with advanced chronic kidney disease (CKD), suggesting that thiazide diuretics can still be beneficial even at lower glomerular filtration rates (GFR).

While diuretics can have adverse effects, recent studies indicate that they do not negatively impact kidney or cardiovascular outcomes in CKD patients, and careful monitoring of electrolytes and GFR is essential for safe use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Revisiting diuretic choice in chronic kidney disease. Ali, S., Navaneethan, SD., Virani, SS., et al.[2023]

In a study involving seven patients with severe renal failure and hypertension, hydrochlorothiazide was found to significantly increase the excretion of sodium and chloride compared to furosemide, suggesting it may be more effective in this population.

Both furosemide and hydrochlorothiazide equally reduced mean arterial blood pressure, but combining the two diuretics did not enhance the effectiveness of hydrochlorothiazide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized trial of furosemide vs hydrochlorothiazide in patients with chronic renal failure and hypertension. Dussol, B., Moussi-Frances, J., Morange, S., et al.[2013]

Loop diuretics are effective in increasing sodium excretion and urine output, even in patients with significantly impaired kidney function, particularly in cases of chronic renal failure and conditions like nephrotic syndrome or chronic heart failure.

While loop diuretics can help manage fluid overload in patients on dialysis, their effectiveness is limited, and high doses can lead to serious side effects such as neurological issues and muscle pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The place of loop diuretics in the treatment of acute and chronic renal failure. Russo, D., Memoli, B., Andreucci, VE.[2010]

Diuretics, including thiazide, loop, and potassium-sparing types, are among the most commonly used medications, highlighting their importance in clinical practice.

While there is substantial information on the pharmacokinetics of diuretics, the metabolism of some remains unclear, and their pharmacodynamic interactions with other drugs can often be anticipated based on their known effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pharmacology of diuretics. Rahn, KH.[2019]

In a study of 3,773 patients prescribed thiazide diuretics, 20.6% experienced low sodium or potassium levels, indicating a significant risk of hyponatraemia and hypokalaemia associated with these medications.

Hyponatraemia was particularly prevalent in older patients, with those over 70 years having nearly four times the odds of developing this condition, highlighting the need for careful monitoring and potentially lower dosing in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thiazide diuretic prescription and electrolyte abnormalities in primary care. Clayton, JA., Rodgers, S., Blakey, J., et al.[2022]

Thiazide diuretics are established as first-line treatments for hypertension and can be used alone or in combination with other medications, but their use in patients with advanced chronic kidney disease (CKD) is often avoided due to safety and efficacy concerns.

An updated review by Minutolo et al. examines the pharmacological properties and clinical trial data of thiazide diuretics in CKD patients, suggesting that these medications may still be effective and safe despite the reluctance to prescribe them in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thiazides in chronic kidney disease: "back to the future". de la Espriella, R., Cobo, M., Núñez, J.[2023]

In a study of 12,722 older adults, chlorthalidone was associated with a higher risk of significant kidney function decline (≥30% eGFR decline) and cardiovascular events compared to hydrochlorothiazide, indicating potential safety concerns with chlorthalidone use.

Chlorthalidone also increased the risk of hypokalemia (low potassium levels), particularly in patients with better kidney function, while no significant differences were found between the two medications regarding dialysis, all-cause mortality, or other electrolyte imbalances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Clinical Outcomes and Safety Associated With Chlorthalidone vs Hydrochlorothiazide in Older Adults With Varying Levels of Kidney Function. Edwards, C., Hundemer, GL., Petrcich, W., et al.[2023]

Potassium-sparing diuretics are particularly useful for cirrhotic patients with ascites, as they provide diuretic effects without the risk of potassium loss, which can be dangerous with stronger diuretics.

These drugs can enhance the effects of other diuretics and can be safely combined with medications like ACE inhibitors, making them versatile in treating conditions such as hypertension and specific syndromes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Potassium-sparing diuretics (spironolactone, triamterene, amylorid)]. Haris, A., Radó, J.[2013]

In a study of 32 patients with chronic kidney disease (CKD) stage 4-5, the combination of bumetanide and chlorthalidone significantly reduced total body water and extracellular water compared to bumetanide with placebo, indicating improved management of volume overload.

The combination treatment also led to a greater reduction in both systolic and diastolic blood pressure over 30 days, demonstrating its efficacy in treating hypertension in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the combination of bumetanide plus chlorthalidone on hypertension and volume overload in patients with chronic kidney disease stage 4-5 KDIGO without renal replacement therapy: a double-blind randomized HEBE-CKD trial. Solis-Jimenez, F., Perez-Navarro, LM., Cabrera-Barron, R., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Combination diuretic treatment in severe heart failure: a randomised controlled trial. [2019]

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

Edema and principles of diuretic use. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Revisiting diuretic choice in chronic kidney disease. [2023]

4. England pubmed.ncbi.nlm.nih.gov

A randomized trial of furosemide vs hydrochlorothiazide in patients with chronic renal failure and hypertension. [2013]

5. Germany pubmed.ncbi.nlm.nih.gov

The place of loop diuretics in the treatment of acute and chronic renal failure. [2010]

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

Clinical pharmacology of diuretics. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Thiazide diuretic prescription and electrolyte abnormalities in primary care. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Thiazides in chronic kidney disease: "back to the future". [2023]

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

Comparison of Clinical Outcomes and Safety Associated With Chlorthalidone vs Hydrochlorothiazide in Older Adults With Varying Levels of Kidney Function. [2023]

10. Hungary pubmed.ncbi.nlm.nih.gov

[Potassium-sparing diuretics (spironolactone, triamterene, amylorid)]. [2013]

11. England pubmed.ncbi.nlm.nih.gov

Effect of the combination of bumetanide plus chlorthalidone on hypertension and volume overload in patients with chronic kidney disease stage 4-5 KDIGO without renal replacement therapy: a double-blind randomized HEBE-CKD trial. [2022]