Prevention of Urinary Stones With Hydration

NCT ID: NCT03244189

Last Updated: 2025-08-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 1658 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-04
• Study Completion Date: 2024-05-31

Brief Summary

A randomized clinical trial to investigate the impact of increased fluid intake and increased urine output on the recurrence rate of urinary stone disease (USD) in adults and children. The primary aim of the trial is to determine whether a multi-component program of behavioral interventions to increase fluid intake will result in reduced risk of stone disease progression over a 2-year period.

Detailed Description

This is a two arm randomized controlled trial that incorporates pragmatic features, an adaptable intervention, patient choice, and remote monitoring of fluid intake through a "smart" water bottle. The study period is 24 months and will enroll approximately 1642 participants. Randomization will be stratified within a study site by age (adult vs. adolescent) and first time vs. recurrent stone former.

Intervention and control arm study participants will receive a smart water bottle that records daily fluid consumption, usual care including guideline-based recommendations of adequate fluid intake to decrease kidney stone recurrence, and periodic 24 hour urine collections, imaging (low-dose CT scan or ultrasound) and follow-up questionnaires.

Conditions

Urinary Stones

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Intervention

Participants in the intervention arm will receive an individualized "fluid prescription", which will be the additional volume of fluid intake needed to maintain a study-specified urine output. This fluid will be consumed from and measured by a smart water bottle. The intervention arm also includes a behavioral program that consists of financial incentives and structured problem solving (SPS) to maintain the recommended fluid intake.

Group Type: EXPERIMENTAL

Fluid prescription

Intervention Type: BEHAVIORAL

The additional amount of fluid that the participant will need to consume each day, using the smart water bottle, in order to meet the study-specified urine output. This fluid is in addition to any other sources of fluid (ex. cups of coffee, bottled sports drink) that the participant consumes each day.

Financial incentive

Intervention Type: BEHAVIORAL

Participants in the Intervention Arm who meet their fluid intake goal on randomly selected days will receive a small payment for that day.

Structured Problem Solving

Intervention Type: BEHAVIORAL

Structure Problem Solving involves interactions with health coaches to help participants develop feasible solutions to overcoming personal barriers to maintaining the prescribed fluid intake.

Control

Participants in the control arm will receive standard care instructions according to American Urological Association (AUA) guidelines to increase overall fluid consumption to achieve study-specified urine output. They will also receive a "smart" water bottle with capability to self-monitor their fluid intake.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Fluid prescription

The additional amount of fluid that the participant will need to consume each day, using the smart water bottle, in order to meet the study-specified urine output. This fluid is in addition to any other sources of fluid (ex. cups of coffee, bottled sports drink) that the participant consumes each day.

Intervention Type: BEHAVIORAL

Financial incentive

Participants in the Intervention Arm who meet their fluid intake goal on randomly selected days will receive a small payment for that day.

Intervention Type: BEHAVIORAL

Structured Problem Solving

Structure Problem Solving involves interactions with health coaches to help participants develop feasible solutions to overcoming personal barriers to maintaining the prescribed fluid intake.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

1. Aged ≥ 12 years

2. At least 1 symptomatic stone event (passage or procedural intervention) within 3 years prior to enrollment or a symptomatic stone event within 5 years if the patient also has new stone formation detected on imaging during the last 5 years. Symptomatic stone defined as any of the following:

1. Stone passage

2. Procedural intervention

3. Radiographically or ultrasonographically confirmed stone with any of the following:

i. Gross hematuria ii. Renal colic or atypical abdominal pain attributed to the stone, as determined by a treating provider iii. A clinical pattern of intermittent symptoms consistent with intermittent obstruction at the ureteropelvic junction, as determined by a treating provider

3. Low 24-hr urine volume

1. ≥18 years old: <2.0 L/day

2. <18 years old: <25 ml/Kg/day up to 2.0L/day

4. Able to provide informed consent (parental permission for children)

5. Owning and willing to use a smartphone or other device (e.g., tablet) compatible with the study-provided wireless enabled "smart" bottle

Exclusion Criteria

1. Spinal cord injury

2. Currently undergoing active treatment for cancer except basal cell skin cancer, or patients with a history of cancer who completed their initial therapy <1 year before screening.

3. Known infectious (struvite), monogenic or other causes of stone disease for which therapies are likely to significantly alter course of stone disease

1. Cystinuria

2. Primary hyperoxaluria

3. Primary xanthinuria

4. Primary hyperparathyroidism

5. Sarcoidosis

6. Medullary sponge kidney

4. History or presence of hyponatremia (serum sodium <130 mmol/L) or hypo-osmolality (serum osmolality <275 mosm/kg)

5. Study participants with comorbidities that preclude high fluid intake or prior surgery precluding high fluid intake or leading to GI fluid losses

1. History of or current Crohn's disease, ulcerative colitis, short gut syndrome (e.g. ileostomy, bowel bypass surgery to treat obesity, small bowel resection), chronic diarrhea, or GI tract ostomy.

2. History of malabsorptive (e.g., Roux-en-Y gastric bypass) or restrictive (e.g., sleeve gastrectomy) bariatric surgery procedures

3. Congestive heart failure

i. NYHA class II or greater, and/or ii. Hospital admission in the past year for heart failure d. Lung disease with a home oxygen requirement e. Chronic kidney disease (eGFR <30 ml/min/1.7 m2 over a 3-month period) i. For adults (age ≥18), we will use the CKD-Epi equation which requires the measurement of serum creatinine only. ii. For children (age <18), we will use the bedside Schwartz (CKiD) formula. f. Nephrotic syndrome (>3.5 grams of protein per 24 hours) g. Cirrhosis with ascites

6. Women who are currently pregnant or planning pregnancy within 2 years.

7. Renal transplant recipient

8. Bedridden study participants (ECOG ≥ 3)

9. Uncorrected anatomical obstruction of the urinary tract

10. History of recurrent urinary tract infections (> 3 UTI/year proven by urine culture)

11. Exclusions due to medication use:

1. Chronic use of lithium

2. Long-term glucocorticoid use (> 7.5 mg prednisone daily for > 30 days prior to enrollment)

3. Intake of narcotic medication on a daily basis for >30 days prior to enrollment

4. Supplemental Vitamin C (> 1 g daily)

12. Individuals with stones that have developed after the initiation of medications that are strongly associated with USD such as carbonic anhydrase inhibitors (acetazolamide, topiramate, zonisamide), high dose vitamin C (> 1 g daily), high dose calcium supplementation (> 1,200 mg daily) AND who have discontinued or plan to discontinue these medications.

13. Individuals with stones composed of medications that may crystallize in the urine (guaifenesin, sulfonamides, triamterene, and the protease inhibitors indinavir and nelfinavir) AND who have discontinued or plan to discontinue these medications.

Note: Individuals who are on long-term medications that increase the risk of stone disease, who cannot stop these medications due to other chronic conditions (e.g., HIV) and who may reduce their risk for stone recurrence through increased fluid intake, will be eligible to participate in the trial. Examples of these medications include:

1. Carbonic anhydrase inhibitors (acetazolamide, topiramate, zonisamide)

2. Medications that may crystallize in the urine (guaifenesin, sulfonamides, triamterene, and the protease inhibitors indinavir and nelfinavir).

14. Study participants <2 yrs life expectancy

15. Non-English Speakers

16. History of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

17. Anatomical urologic abnormalities including ileal conduits, horseshoe kidney, megaureter or solitary kidney.

18. Psychiatric conditions impairing compliance with the study

19. Vulnerable population (prisoner and/or cognitive impairment that the investigator feels will impact the study participant's ability to participate in the protocol)

20. Individual who will be unable to participate in the protocol in the judgment of the investigator.

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Charles Scales, MD, MSHS

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Mayo Clinic

Rochester, Minnesota, United States

Washington University, St. Louis

St Louis, Missouri, United States

Cleveland Clinic

Cleveland, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Children's Hospital

Dallas, Texas, United States

University of Texas Southwestern

Dallas, Texas, United States

University of Washington

Seattle, Washington, United States

Countries

United States

References

Wessells H, Lieske JC, Lai HH, Al-Khalidi HR, Desai AC, Harper JD, Kirkali Z, Maalouf NM, McCune R, Reese PP, Scales CD, Tasian GE; NIDDK Urinary Stone Disease Research Network. Adjudication of Self-reported Symptomatic Stone Recurrence in the Prevention of Urinary Stones With Hydration Trial. Urology. 2024 Dec;194:27-35. doi: 10.1016/j.urology.2024.08.026. Epub 2024 Sep 4.

Reference Type: DERIVED

PMID: 39242045 (View on PubMed)

Reese PP, Shah S, Funsten E, Amaral S, Audrain-McGovern J, Koepsell K, Wessells H, Harper JD, McCune R, Scales CD Jr, Kirkali Z, Maalouf NM, Lai HH, Desai AC, Al-Khalidi HR, Tasian GE. Using structured problem solving to promote fluid consumption in the prevention of urinary stones with hydration (PUSH) trial. BMC Nephrol. 2024 May 28;25(1):183. doi: 10.1186/s12882-024-03605-y.

Reference Type: DERIVED

PMID: 38807063 (View on PubMed)

Scales CD Jr, Desai AC, Harper JD, Lai HH, Maalouf NM, Reese PP, Tasian GE, Al-Khalidi HR, Kirkali Z, Wessells H; Urinary Stone Disease Research Network. Prevention of Urinary Stones With Hydration (PUSH): Design and Rationale of a Clinical Trial. Am J Kidney Dis. 2021 Jun;77(6):898-906.e1. doi: 10.1053/j.ajkd.2020.09.016. Epub 2020 Nov 16.

Reference Type: DERIVED

PMID: 33212205 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://usdrn.org/

The Urinary Stone Disease Research Network (USDRN) website. The USDRN is the program conducting the PUSH study.

Other Identifiers

1U01DK110988

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Pro00083271

Identifier Type: -

Identifier Source: org_study_id