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Trial registered on ANZCTR


Registration number
ACTRN12614001216606
Ethics application status
Approved
Date submitted
22/10/2014
Date registered
19/11/2014
Date last updated
15/11/2021
Date data sharing statement initially provided
21/01/2020
Date results information initially provided
21/01/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Trial of prescribed water intake in polycystic kidney disease
Scientific title
Randomised controlled trial to determine the efficacy and safety of prescribed water intake to prevent kidney failure due to Autosomal Dominant Polycystic Kidney Disease (PREVENT-ADPKD)
Secondary ID [1] 285522 0
nil
Universal Trial Number (UTN)
Nil
Trial acronym
PREVENT-ADPKD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Autosomal Dominant Polycystic Kidney Disease (ADPKD) 293336 0
Condition category
Condition code
Renal and Urogenital 293599 293599 0 0
Kidney disease
Human Genetics and Inherited Disorders 293791 293791 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Group A- Standard treatment and ad libitum water consumption for 36 months. Standard treatment is defined as generic approaches (weight management, salt restriction, smoking cessation, blood pressure control) to slow the progression of chronic kidney disease; which include the standard care from the participants' usual physician.
Group B- Standard treatment and prescribed water consumption for 36 months. In Group B, the individualized daily water prescription to reduce the urine osmolality will be calculated using the free water clearance formula. The study dietitian provided personalized counseling for consuming the water prescription, considering lifestyle, dietary solute intake, and preferences. In addition, patients self-monitored urine specific gravity (USG) (daily for the first 2 weeks, twice weekly for the first 6 months, and then as needed) to keep it below 1.010. The water prescription was re-calculated during follow-up visits using 24-hour urine osmolality (3-monthly during in the first year and then 6-monthly in the second and third years). Patients in both groups underwent the same follow-up tests and visits.
Intervention code [1] 290463 0
Treatment: Other
Comparator / control treatment
Standard treatment and ad libitum water consumption for 36 months. Standard treatment is defined as generic approaches (weight management, salt restriction, smoking cessation, blood pressure control) to slow the progression of chronic kidney disease; which include the standard care from the participants' usual physician.
Control group
Active

Outcomes
Primary outcome [1] 293411 0
Annualized rate of change (slope) in Ht-TKV (total kidney volume of both kidneys corrected for height) from baseline to Month 18 and Month 36 timepoints normalized as a percentage,
Timepoint [1] 293411 0
From Baseline to month 36
Secondary outcome [1] 310973 0
Treatment efficacy measured by changes in markers of systemic arginine vasopressin (AVP) activity; serum copeptin and 24-hour urine osmolality and volume.
Timepoint [1] 310973 0
From Baseline to month 36
Secondary outcome [2] 311408 0
Treatment efficacy measured by change in markers of Kidney Disease Progression: Rate of eGFR decline from post-randomisation (0 and 3 months) to Month 36; resting mean arterial pressure (MAP); urine albumin to creatinine ratio and kidney pain.
Timepoint [2] 311408 0
From 0 (baseline) and 3 months to Month 36
Secondary outcome [3] 311410 0
Treatment adherence measured by proportion of participants with 24 hr-urine osmolality <300 mosmol/kg at all timepoints.
Timepoint [3] 311410 0
From Baseline to month 36
Secondary outcome [4] 311412 0
Safety and tolerability assessed by proportion of participants with serum Na+ <130 mmol/L.

This will be monitored regularly by monitoring blood sodium levels during the study. If the sodium levels go below a minimum level, the participant will be wtihdrawn from the intervention (but continued to be followed up) and appropriate medical management undertaken.
Timepoint [4] 311412 0
From baseline to Month 36
Secondary outcome [5] 320078 0
Treatment acceptability measured by the proportion of patients reporting that water intake can be maintained life-long.
Timepoint [5] 320078 0
From Baseline to month 36
Secondary outcome [6] 320079 0
Treatment acceptability measured by the proportion of patients withdrawing from the study.
Timepoint [6] 320079 0
From Baseline to month 36
Secondary outcome [7] 320080 0
Treatment efficacy measured by a composite endpoint of time to investigator-assessed clinical progression, based on the TEMPO 3:4 protocol, defined as: worsening hypertension (changes in blood-pressure category, as defined in the protocol, or worsening of hypertension requiring an increase in hypertensive treatment); clinically significant kidney pain necessitating medical leave, pharmacologic treatment (narcotic or last-resort analgesic agents), or invasive intervention; worsening kidney function from baseline (a 25% reduction in eGFR from the value at baseline, reproduced after at least 2 weeks); worsening kidney function from week 12 (a 25% reduction in eGFR from the value at week 12, reproduced after at least 2 weeks); worsening albuminuria.
Timepoint [7] 320080 0
From Baseline to Month 36.
Secondary outcome [8] 403037 0
Treatment adherence measured by proportion of participants with 24-hr urine osmolality <300 mosmol/kg >50% of timepoints.
Timepoint [8] 403037 0
From baseline to Month 36
Secondary outcome [9] 403038 0
Safety and tolerability assessed by episodes of adverse events (AEs)/serious AEs (SAEs).
Timepoint [9] 403038 0
Baseline to Month 36
Secondary outcome [10] 403039 0
Treatment acceptability measured by changes in Treatment Acceptability Questionnaire
Timepoint [10] 403039 0
Baseline to Month 36

Eligibility
Key inclusion criteria
1. Adult patients (18-67 years of age) providing informed consent
2. Adult patients with a diagnosis of ADPKD
3. eGFR of 30 mL/min/1.73m2 within 12 weeks of randomisation as determined by the chronic kidney disease epidemiology collaboration (CKD EPI) formula
Minimum age
18 Years
Maximum age
67 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients who in the opinion of the trial investigators present a safety risk (including serum Na+ <135 mmol/L at screening; requirement for concomitant medications with a high risk of precipitating hyponatraemia, such as chronic use of diuretics; concomitant medical conditions that require fluid restriction, such as heart failure, chronic liver disease, nephrotic syndrome or generalised oedema; abnormalities in the voiding mechanism; pregnant or breast-feeding women).
2. Contraindication to or interference with MRI assessments (e.g. ferro-magnetic prostheses, aneurysm clips, severe claustrophobia or other contraindications)
3. Patients who are unlikely to adequately comply with trial’s procedures (such as history of non-compliance with anti-hypertensive or other important medical therapy; history of substance abuse within the previous 2 years)
4. Patients having concomitant illnesses or treatments likely to confound endpoint assessments (such as advanced and poorly controlled diabetes; evidence of significant renal disease not due to ADPKD, such as active glomerulonephritis, renal cancer or single kidney; severe co-morbid illnesses)
5. Patients participating in other clinical trials to slow ADPKD or CKD
6. Patients with Baseline TKV in Mayo Clinic Imaging Classes 1A

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients will be randomly allocated in a uniform 1:1 ratio to either Group A or B. Randomisation is centrally controlled and concealed with a secure web based randomisation service.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation is centrally controlled and concealed with a secure web based randomisation service. Participants will be randomly allocated in a uniform 1:1 ratio (in permuted blocks), stratified according to baseline eGFR level.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Nil
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The sample size will be determined assuming an annual rate of increase in Ht-TKV of 5.5+/-3.8% per year (mean+SD),30 and an enrolment of 180 patients (n=90 per arm) was predicted to have 87% power to detect a difference of 1.9% per year in Ht-TKV using a two-sided test and 0.05 level of significance, based on a drop-out rate of 15%. The primary endpoint (annualized rate of change of Ht-TKV) will be analyzed using a linear mixed effect model with log10 Ht-TKV of the baseline, Month 18 and Month 36 MR scans as the endpoints and will include random intercept and slope.. Where the Ht-TKV value is missing at the Month 18 or Month 36 timepoints, the data will be imputed under the missing at random (MAR) assumption using multiple imputations with 100 resamples drawn. For secondary endpoint analysis, no imputation will be performed, and data will be analyzed using a mixed model with repeated measurements (MMRM). An unstructured variance-covariance matrix was used. Least squares mean, least squares mean treatment differences, and their associated 95% confidence intervals will be calculated. All statistical analyses will be performed in the intention-to-treat sample with SAS software, version 9.4.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/12/2015
Actual
9/12/2015
Date of last participant enrolment
Anticipated
30/06/2017
Actual
11/05/2018
Date of last data collection
Anticipated
31/05/2021
Actual
30/06/2021
Sample size
Target
180
Accrual to date
Final
187
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 3057 0
Westmead Hospital - Westmead
Recruitment hospital [2] 3058 0
Nepean Hospital - Kingswood
Recruitment hospital [3] 7274 0
Simon Roger Gosford Renal Research - Gosford
Recruitment hospital [4] 7275 0
Norwest Private Hospital - Bella Vista
Recruitment hospital [5] 15655 0
Liverpool Hospital - Liverpool
Recruitment hospital [6] 15656 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [7] 15657 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [8] 15658 0
Prince of Wales Hospital - Randwick
Recruitment hospital [9] 15659 0
St George Hospital - Kogarah
Recruitment hospital [10] 15660 0
John Hunter Hospital - New Lambton
Recruitment hospital [11] 15661 0
Mater Sydney - North Sydney
Recruitment hospital [12] 15662 0
Wollongong Hospital - Wollongong
Recruitment postcode(s) [1] 29067 0
2031 - Randwick
Recruitment postcode(s) [2] 29070 0
2060 - North Sydney
Recruitment postcode(s) [3] 8828 0
2145 - Westmead
Recruitment postcode(s) [4] 15041 0
2153 - Bella Vista
Recruitment postcode(s) [5] 29064 0
2170 - Liverpool
Recruitment postcode(s) [6] 29068 0
2217 - Kogarah
Recruitment postcode(s) [7] 15040 0
2250 - Gosford
Recruitment postcode(s) [8] 29069 0
2305 - New Lambton
Recruitment postcode(s) [9] 29071 0
2500 - Wollongong
Recruitment postcode(s) [10] 8829 0
2750 - Penrith
Recruitment postcode(s) [11] 29066 0
4102 - Woolloongabba
Recruitment postcode(s) [12] 29065 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 290119 0
Hospital
Name [1] 290119 0
Western Sydney Local Health District
Country [1] 290119 0
Australia
Funding source category [2] 290123 0
University
Name [2] 290123 0
University of Sydney
Country [2] 290123 0
Australia
Funding source category [3] 292738 0
Commercial sector/Industry
Name [3] 292738 0
Danone Nutricia Research
Country [3] 292738 0
France
Funding source category [4] 309697 0
Government body
Name [4] 309697 0
National Health and Medical Research Council
Country [4] 309697 0
Australia
Funding source category [5] 309698 0
Charities/Societies/Foundations
Name [5] 309698 0
Polycystic Kidney Disease Foundation of Australia
Country [5] 309698 0
Australia
Funding source category [6] 309699 0
Charities/Societies/Foundations
Name [6] 309699 0
Westmead Medical Research Foundation
Country [6] 309699 0
Australia
Primary sponsor type
Hospital
Name
Western Sydney Local Health District
Address
Corner of Hawkebury and Darcy Roads,
Westmead
NSW 2145
Country
Australia
Secondary sponsor category [1] 288838 0
None
Name [1] 288838 0
-
Address [1] 288838 0
-
Country [1] 288838 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291835 0
WSLHD Human Research Ethics Committee (HREC)
Ethics committee address [1] 291835 0
Corner of Hawkesbury and Darcy Roads,
Westmead, NSW, 2145
Ethics committee country [1] 291835 0
Australia
Date submitted for ethics approval [1] 291835 0
01/12/2015
Approval date [1] 291835 0
09/12/2015
Ethics approval number [1] 291835 0

Summary
Brief summary
ADPKD is an inherited condition, characterized by the growth of hundreds of cysts (fluid-filled sacs) in the kidney. This results in an enlarged kidney and pain, high blood pressure and an increased risk of chronic kidney disease. Kidney failure usually develops in late adulthood in about half of affected people. There is currently no treatment that can cure ADPKD or stop cysts forming and growing in the kidneys.

In the last few years, people with ADPKD have been advised to drink more water to suppress anti-diuretic hormone (ADH, or vasopressin). However, it is not clear if this approach is feasible in the long-term and without risk and/or if there is an ideal amount of water to drink that will benefit disease progression.

The aim of this study is to determine the efficacy and safety of prescribed water intake in ADPKD.

Eligible patients with ADPKD will be randomised (1:1) to either:
Group A (control) to continue with their usual (ad libitum) water consumption (including standard treatment) or Group B (intervention) to adjust their daily water intake to reduce the urine osmolality to less than or equal to 270 mosmol/L for the next 36 months in addition to their standard treatment. The volume of prescribed water consumption will be calculated according to free water clearance based on baseline and progress measurements of 24 hour urine collection.

All patients will be expected to have blood collections at 3, 6, 9, 12, 18, 24, 30 and 36 months. In Group B subjects, additional samples will be collected at Week 3 and 6 for safety check and also titration of the water prescription.

After the Month 36 visit, Group B patients may return to their previous ad libitum water consumption habits.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 52198 0
A/Prof Gopala Rangan
Address 52198 0
Westmead Institute for Medical Research
Centre for Transplant and Renal Research
176 Hawkesbury Road
Westmead, NSW 2145
Country 52198 0
Australia
Phone 52198 0
+61 2 88906962
Fax 52198 0
Email 52198 0
preventadpkd@sydney.edu.au
Contact person for public queries
Name 52199 0
A/Prof Gopala Rangan
Address 52199 0
Westmead Institute for Medical Research
Centre for Transplant and Renal Research
176 Hawkesbury Road
Westmead, NSW 2145
Country 52199 0
Australia
Phone 52199 0
+61 2 88906962
Fax 52199 0
Email 52199 0
preventadpkd@sydney.edu.au
Contact person for scientific queries
Name 52200 0
A/Prof Gopala Rangan
Address 52200 0
Westmead Institute for Medical Research
Centre for Transplant and Renal Research
176 Hawkesbury Road
Westmead, NSW 2145
Country 52200 0
Australia
Phone 52200 0
+61 2 88906962
Fax 52200 0
Email 52200 0
preventadpkd@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseManagement of autosomal-dominant polycystic kidney disease - State-of-the-art.2018https://dx.doi.org/10.1093/ckj/sfy103
EmbaseRelative validity of a beverage frequency questionnaire used to assess fluid intake in the autosomal dominant polycystic kidney disease population.2018https://dx.doi.org/10.3390/nu10081051
EmbaseOsmoregulation in polycystic kidney disease: Relationship with cystogenesis and hypertension.2018https://dx.doi.org/10.1159/000488125
EmbasePatient Survey of current water Intake practices in autosomal dominant Polycystic kidney disease: The SIPs survey.2017https://dx.doi.org/10.1093/ckj/sfw153
EmbaseParticipant Perceptions in a Long-term Clinical Trial of Autosomal Dominant Polycystic Kidney Disease.2023https://dx.doi.org/10.1016/j.xkme.2023.100691
EmbaseCurrent and emerging treatment options to prevent renal failure due to autosomal dominant polycystic kidney disease.2020https://dx.doi.org/10.1080/21678707.2020.1804859
EmbaseAssessment of dietary sodium intake using the scored salt questionnaire in autosomal dominant polycystic kidney disease.2020https://dx.doi.org/10.3390/nu12113376
EmbaseAutosomal dominant polycystic kidney disease.2019https://dx.doi.org/10.1016/S0140-6736%2818%2932782-X
EmbaseDietary Aspects and Drug-Related Side Effects in Autosomal Dominant Polycystic Kidney Disease Progression.2022https://dx.doi.org/10.3390/nu14214651
Dimensions AIInsights Into the Molecular Mechanisms of Polycystic Kidney Diseases2021https://doi.org/10.3389/fphys.2021.693130
N.B. These documents automatically identified may not have been verified by the study sponsor.