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| ID | Type | Description | Link |
|---|---|---|---|
| 1U01DK110988 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention | Experimental | 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. |
|
| Control | No Intervention | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fluid prescription | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Baseline through approximately 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Asymptomatic Formation of New Stone | Up to approximately 24 months | |
| 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Inclusion Criteria:
Aged ≥ 12 years
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:
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
Low 24-hr urine volume
Able to provide informed consent (parental permission for children)
Owning and willing to use a smartphone or other device (e.g., tablet) compatible with the study-provided wireless enabled "smart" bottle
Exclusion Criteria:
Spinal cord injury
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.
Known infectious (struvite), monogenic or other causes of stone disease for which therapies are likely to significantly alter course of stone disease
History or presence of hyponatremia (serum sodium <130 mmol/L) or hypo-osmolality (serum osmolality <275 mosm/kg)
Study participants with comorbidities that preclude high fluid intake or prior surgery precluding high fluid intake or leading to GI fluid losses
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
Women who are currently pregnant or planning pregnancy within 2 years.
Renal transplant recipient
Bedridden study participants (ECOG ≥ 3)
Uncorrected anatomical obstruction of the urinary tract
History of recurrent urinary tract infections (> 3 UTI/year proven by urine culture)
Exclusions due to medication use:
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.
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:
Study participants <2 yrs life expectancy
Non-English Speakers
History of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
Anatomical urologic abnormalities including ileal conduits, horseshoe kidney, megaureter or solitary kidney.
Psychiatric conditions impairing compliance with the study
Vulnerable population (prisoner and/or cognitive impairment that the investigator feels will impact the study participant's ability to participate in the protocol)
Individual who will be unable to participate in the protocol in the judgment of the investigator.
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| Name | Affiliation | Role |
|---|---|---|
| Charles Scales, MD, MSHS | Duke University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic | Rochester | Minnesota | 55905 | United States | ||
| Washington University, St. Louis |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41864748 | Derived | 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. | |
| 39242045 | Derived | 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. |
| Label | URL |
|---|---|
| The Urinary Stone Disease Research Network (USDRN) website. The USDRN is the program conducting the PUSH study. | View source |
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Data and samples, for subjects who consent to sharing, will be sent to the NIDDK Data and Biological Samples Repository following database lock.
2 years after the last visit of the last participant randomized.
Anyone with access to the NIDDK Data and Biological Samples Repository
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. 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. 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. 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. 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. 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. 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Posted | Count of Participants | Participants | Baseline through approximately 24 months |
|
Up to approximately 24 months
"Hyponatremia requiring hospitalization" was the only Serious Adverse Event (SAE) collected for the study. "Asymptomatic hyponatremia" was the only non-serious AE collected.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. 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. 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. 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hyponatremia requiring hospitalization | Metabolism and nutrition disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Asymptomatic hyponatremia | Metabolism and nutrition disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Charles D. Scales Jr, MD MSHS FACS | Duke University | 919-684-1999 | chuck.scales@duke.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 4, 2020 | Jul 17, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D014545 | Urinary Calculi |
| D007669 | Kidney Calculi |
| ID | Term |
|---|---|
| D052878 | Urolithiasis |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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The Principal Investigator and site investigators, along with the primary study statistician will remind blinded throughout the trial.
|
| Financial incentive | 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 | 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. |
|
| Baseline through approximately 24 months |
| Number of Participants With Symptomatic Stone Recurrence, Asymptomatic Stone Formation, or Increase of Existing Stone by ≥2 mm in Any Dimension | Baseline through approximately 24 months |
| 24-hour Urine Total Volume | 6, 12, 18, and 24 months |
| 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. | Baseline, 6, 12, 18, and 24 months |
| Baseline through approximately 24 months |
| 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 |
| 38807063 | Derived | 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. |
| 33212205 | Derived | 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. |
| Physician Decision |
|
| Pregnancy |
|
| Protocol Violation |
|
| Withdrawal by Subject |
|
| Technical Problems |
|
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | 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. |
|
|
|
| Secondary | Number of Participants With Asymptomatic Formation of New Stone | Posted | Count of Participants | Participants | Up to approximately 24 months |
|
|
|
|
| Secondary | 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). | Posted | Count of Participants | Participants | Baseline through approximately 24 months |
|
|
|
|
| Secondary | Number of Participants With Symptomatic Stone Recurrence, Asymptomatic Stone Formation, or Increase of Existing Stone by ≥2 mm in Any Dimension | Posted | Count of Participants | Participants | Baseline through approximately 24 months |
|
|
|
| Secondary | 24-hour Urine Total Volume | Posted | Median | 95% Confidence Interval | L/day | 6, 12, 18, and 24 months |
|
|
|
| Secondary | 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. | Participants with CASUS data available at each timepoint. | Posted | Mean | Standard Deviation | score on a scale | Baseline, 6, 12, 18, and 24 months |
|
|
|
| Other Pre-specified | 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. | Not Posted | Baseline through approximately 24 months | Participants |
| 0 |
| 826 |
| 0 |
| 826 |
| 12 |
| 826 |
| EG001 | 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. | 2 | 832 | 0 | 832 | 2 | 832 |
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| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002137 | Calculi |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D053040 | Nephrolithiasis |
| D007674 | Kidney Diseases |
| 18 months |
|
| 24 months |
|
| 6 months |
|
|
| 12 months |
|
|
| 18 months |
|
|
| 24 months |
|
|