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CompletedNCT03244189PUSHUpdated Jun 25, 2026Results posted

Prevention of Urinary Stones With Hydration

An interventional study of Fluid prescription and Financial incentive in Urinary Stones, sponsored by Duke University. Completed at 8 sites in United States. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2026-06-25.

Sponsored by Duke University · Not applicable, Interventional, and Prevention

Phase
Not applicable
Study type
Interventional
Enrollment
1,658
Allocation
Randomized
Ages
12 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Urinary Stones

Keywords

  • Urinary Stone Disease
  • Kidney Stone
  • Urinary Calculi
03

Who can participate

Ages eligible
12 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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.
04

Study design

Phase
Not applicable
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Investigator)
Enrollment
1,658 participants (actual)

Study arms

  • Experimental
    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.

    Behavioral: Fluid prescription · Behavioral: Financial incentive · Behavioral: Structured Problem Solving

  • No intervention
    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.

Interventions

  • BehavioralFluid 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.

  • BehavioralFinancial incentive

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

  • BehavioralStructured 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.

05

What researchers measure

Primary outcomes

  1. Number of Participants With a Symptomatic Stone Event

    Having a symptomatic stone event was defined as meeting any 1 of 2 criteria - stone passage or a procedural intervention for a stone (whether the stone was causing symptoms or not).

    Time frame: Baseline through approximately 24 months

Secondary outcomes

  1. Number of Participants With Asymptomatic Formation of New Stone

    Time frame: Up to approximately 24 months

  2. Number of Participants With Growth of Existing Stone by ≥ 2 mm in Any Dimension

    Comparison of the size of any stone on first observation versus later observations or at passage. Will be measured primarily through imaging (CT scan and ultrasound).

    Time frame: Baseline through approximately 24 months

  3. Number of Participants With Symptomatic Stone Recurrence, Asymptomatic Stone Formation, or Increase of Existing Stone by ≥2 mm in Any Dimension

    Time frame: Baseline through approximately 24 months

  4. 24-hour Urine Total Volume

    Time frame: 6, 12, 18, and 24 months

  5. Comprehensive Assessment of Self-Reported Urinary Symptoms (CASUS)

    The CASUS is a tool used to assess lower urinary tract symptoms (LUTS) in individuals, providing a comprehensive evaluation of various urinary issues. It's designed to capture a wide range of symptoms, including storage, voiding, post-micturition, urgency, incontinence, and abnormal bladder sensations. The total score ranges from 0 to 38, where a higher score indicates greater urinary symptoms.

    Time frame: Baseline, 6, 12, 18, and 24 months

Other outcomes

  1. Costs of Study Interventions and Treatments for USD During the Follow-up Period

    To estimate study intervention costs, we will use a tool specifically designed to estimate costs associated with patient-centered interventions (R01NR011873). The costs of medical resource use will be assigned based on payment schedules (e.g., Medicare). To incorporate potential differences in health-related quality of life experienced by participants in the cost-effectiveness analysis, health state utilities will be estimated from existing literature. Full details of the economic analysis will be specified in the Economic Statistical Analysis Plan.

    Time frame: Baseline through approximately 24 months

06

Results

Posted Aug 5, 2025

Participant flow

Participant flow — Overall Study
MilestoneInterventionControl
Started826832
Completed676691
Not completed150141
Withdrew: Death02
Withdrew: Lost to follow-up92107
Withdrew: Physician decision42
Withdrew: Pregnancy75
Withdrew: Protocol violation02
Withdrew: Withdrawal by subject4523
Withdrew: Technical problems20

Outcome measures

PrimaryNumber of Participants With a Symptomatic Stone Event

Having a symptomatic stone event was defined as meeting any 1 of 2 criteria - stone passage or a procedural intervention for a stone (whether the stone was causing symptoms or not).

Time frame:
Baseline through approximately 24 months
Reported as:
Count of participants · Participants
Number of Participants With a Symptomatic Stone Event
ParticipantsInterventionControl
Number of Participants With a Symptomatic Stone Event154165
Statistical analysis
  • Intervention vs Control · Hazard ratio (hr): 0.96 · 95% CI 0.77 to 1.20
SecondaryNumber of Participants With Asymptomatic Formation of New Stone
Time frame:
Up to approximately 24 months
Reported as:
Count of participants · Participants
Number of Participants With Asymptomatic Formation of New Stone
ParticipantsInterventionControl
Number of Participants With Asymptomatic Formation of New Stone8283
Statistical analysis
  • Intervention vs Control · Odds ratio (or): 0.99 · 95% CI 0.72 to 1.37
SecondaryNumber of Participants With Growth of Existing Stone by ≥ 2 mm in Any Dimension

Comparison of the size of any stone on first observation versus later observations or at passage. Will be measured primarily through imaging (CT scan and ultrasound).

Time frame:
Baseline through approximately 24 months
Reported as:
Count of participants · Participants
Number of Participants With Growth of Existing Stone by ≥ 2 mm in Any Dimension
ParticipantsInterventionControl
Number of Participants With Growth of Existing Stone by ≥ 2 mm in Any Dimension4532
Statistical analysis
  • Intervention vs Control · Odds ratio (or): 1.44 · 95% CI 0.91 to 2.29
SecondaryNumber of Participants With Symptomatic Stone Recurrence, Asymptomatic Stone Formation, or Increase of Existing Stone by ≥2 mm in Any Dimension
Time frame:
Baseline through approximately 24 months
Reported as:
Count of participants · Participants
Number of Participants With Symptomatic Stone Recurrence, Asymptomatic Stone Formation, or Increase of Existing Stone by ≥2 mm in Any Dimension
ParticipantsInterventionControl
Number of Participants With Symptomatic Stone Recurrence, Asymptomatic Stone Formation, or Increase of Existing Stone by ≥2 mm in Any Dimension232236
Secondary24-hour Urine Total Volume
Time frame:
6, 12, 18, and 24 months
Reported as:
Median · L/day
24-hour Urine Total Volume
L/dayInterventionControl
6 months1.81 (1.30 to 2.38)1.58 (1.10 to 2.18)
12 months1.70 (1.24 to 2.29)1.57 (1.14 to 2.20)
18 months1.70 (1.25 to 2.26)1.55 (1.13 to 2.09)
24 months1.55 (1.18 to 2.10)1.47 (1.02 to 20.3)
SecondaryComprehensive Assessment of Self-Reported Urinary Symptoms (CASUS)

The CASUS is a tool used to assess lower urinary tract symptoms (LUTS) in individuals, providing a comprehensive evaluation of various urinary issues. It's designed to capture a wide range of symptoms, including storage, voiding, post-micturition, urgency, incontinence, and abnormal bladder sensations. The total score ranges from 0 to 38, where a higher score indicates greater urinary symptoms.

Time frame:
Baseline, 6, 12, 18, and 24 months
Reported as:
Mean · score on a scale
Comprehensive Assessment of Self-Reported Urinary Symptoms (CASUS)
score on a scaleInterventionControl
Baseline6.11 ± 3.2985.94 ± 3.311
6 months6.23 ± 3.1976.11 ± 3.280
12 months6.26 ± 3.4426.05 ± 3.517
18 months6.11 ± 3.2676.11 ± 3.459
24 months6.00 ± 3.2836.01 ± 3.373
Other pre-specifiedCosts of Study Interventions and Treatments for USD During the Follow-up Period

To estimate study intervention costs, we will use a tool specifically designed to estimate costs associated with patient-centered interventions (R01NR011873). The costs of medical resource use will be assigned based on payment schedules (e.g., Medicare). To incorporate potential differences in health-related quality of life experienced by participants in the cost-effectiveness analysis, health state utilities will be estimated from existing literature. Full details of the economic analysis will be specified in the Economic Statistical Analysis Plan.

Time frame:
Baseline through approximately 24 months

Results for this outcome have not been posted.

Adverse events

Collected over Up to approximately 24 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Intervention0/826 (0%)0/826 (0%)12/826 (1.5%)
Control2/832 (0.2%)0/832 (0%)2/832 (0.2%)
Most frequent serious events
Most frequent serious events
EventInterventionControl
Hyponatremia requiring hospitalizationMetabolism and nutrition disorders0/8260/832
Most frequent other events
Most frequent other events
EventInterventionControl
Asymptomatic hyponatremiaMetabolism and nutrition disorders12/8262/832

Baseline characteristics

Age, Continuous
Age, Continuous(years)InterventionControlTotal
Median45 (30 to 60)44 (27 to 58)44 (29 to 59)
Sex: Female, Male
Sex: Female, Male(Participants)InterventionControlTotal
Female469477946
Male357355712
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)InterventionControlTotal
Hispanic or Latino4656102
Not Hispanic or Latino7617571518
Unknown or Not Reported191938
Race (NIH/OMB)
Race (NIH/OMB)(Participants)InterventionControlTotal
American Indian or Alaska Native033
Asian222547
Native Hawaiian or Other Pacific Islander224
Black or African American5558113
White7327191451
More than one race71421
Unknown or Not Reported81119
Region of Enrollment
Region of Enrollment(Participants)InterventionControlTotal
United States8268321658
07

Study locations

8 sites
  • Mayo Clinic
    Rochester, Minnesota 55905, United States
  • Washington University, St. Louis
    St Louis, Missouri 63110, United States
  • Cleveland Clinic
    Cleveland, Ohio 44195, United States
  • University of Pennsylvania
    Philadelphia, Pennsylvania 19104, United States
  • Children's Hospital of Philadelphia
    Philadelphia, Pennsylvania 19146, United States
  • Children's Hospital
    Dallas, Texas 75390, United States
  • University of Texas Southwestern
    Dallas, Texas 75390, United States
  • University of Washington
    Seattle, Washington 98195, United States
08

References and documents

Publications

  • Desai AC, Maalouf NM, Harper JD, Sivalingam S, Lieske JC, Lai HH, Reese PP, Wessells H, Yang H, Al-Khalidi HR, Kirkali Z, Tasian GE, Scales CD Jr; Urinary Stone Disease Network Investigators. Prevention of urinary stones with hydration: a randomised clinical trial of an adherence intervention. Lancet. 2026 Mar 21;407(10534):1171-1181. doi: 10.1016/S0140-6736(25)02637-6. PubMed 41864748 ↗
  • 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. PubMed 39242045 ↗
  • 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. PubMed 38807063 ↗
  • 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. PubMed 33212205 ↗

Study documents

  • Protocol and statistical analysis plan · Feb 4, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Data and samples, for subjects who consent to sharing, will be sent to the NIDDK Data and Biological Samples Repository following database lock.

Supporting information: Study protocol, Icf, Csr, Analytic code

09

Registry details

Key details

Study ID
NCT03244189
Lead sponsor
Duke University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Responsible party
Sponsor
First posted
Aug 9, 2017
Start date
Oct 4, 2017
Primary completion
May 18, 2024
Completion
May 31, 2024
Results posted
Aug 5, 2025
Last update
Jun 25, 2026

Study contacts

Charles Scales, MD, MSHS
principal investigator · Duke University

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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