Clinical trial NCT03244189: Prevention of Urinary Stones With Hydration
Official title: Prevention of Urinary Stones With Hydration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Urinary Stones
Keywords: Urinary Stone Disease
Kidney Stone
Urinary Calculi
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2017-08-09
Enrollment: 1658
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Stone passage observed and/or captured by the study participant.
timeFrame: From Baseline through 24 months.
measure: Procedural intervention for symptomatic stone
timeFrame: From Baseline through 24 months.
measure: Any procedural intervention for removal of asymptomatic renal or ureteral stone
timeFrame: From Baseline through 24 months.
Secondary outcomes:
measure: Asymptomatic formation of new stone detected by imaging
timeFrame: From Baseline through 24 months.
measure: Growth of existing stone by ≥ 2 mm in any dimension detected by imaging
timeFrame: From Baseline through 24 months.
measure: Composite outcome: symptomatic stone recurrence, asymptomatic stone formation, increase of existing stone by ≥2 mm in any dimension detected by imaging
timeFrame: From Baseline through 24 months.
measure: 24 hour urine total volume
timeFrame: From Baseline through 24 months.
measure: Costs of study interventions and treatments for USD during the follow-up period
timeFrame: Compared total between Baseline and the Month 24 visit.
measure: Presence of lower urinary tract symptoms (Comprehensive Assessment of Self-reported Urinary Symptoms)
timeFrame: From Baseline through the Month 24 visit.
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University, St. Louis
state: Missouri
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Dallas
country: United States
facility: Children's Hospital
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: Duke University
name: Charles Scales, MD, MSHS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.