UMIN-CTR Clinical Trial

Basic information
Public title	Longitudinal Efficacy and Safety Study of Tolvaptan on Autosomal Dominant Polycystic Kidney Disease Patients
Acronym	Efficacy Study of Tolvaptan on ADPKD Patients [LET-PKD study]
Scientific Title	Longitudinal Efficacy and Safety Study of Tolvaptan on Autosomal Dominant Polycystic Kidney Disease Patients
Scientific Title:Acronym	Efficacy Study of Tolvaptan on ADPKD Patients [LET-PKD study]
Region	Japan

Condition
Condition	Autosomal Dominant Polycystic Kidney Disease
Classification by specialty	Urology
Classification by malignancy	Others
Genomic information	YES

Objectives
Narrative objectives1	1. Primary Objective To assess the effect of tolvaptan on the percent change (% per year) in TKV volumetrically measured by MRT -Supplementary assessment- Using "a" calculated from the following equation: [HtTKV at age t]= K (1+eAHTKV-a/100)t, as an indicator, the effect of tolvaptan on HtTKV slope will be supplementarily assessed. 2. Secondary Objectives 1)To assess the effects of tolvaptan on renal function 2)To assess the safety of tolvaptan 3)To assess the effects of tolvaptan based on the results of 24-hour urine collection, blood tests, inulin clearance, and TKV 4)To investigate inulin clearance and the clinical condition of ADPKD 5)To assess the relationship (correlation) between eGFR estimated using different formulae and inulin clearance, and the impact of tolvaptan on this correlation 6)To analyze the association between the results of DNA analysis (pathogenic genotype and mutation site) and the effect of tolvaptan in patients who have no available DNA analysis data and will newly undergo DNA analysis in the study
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Others
Trial characteristics_2	Others
Developmental phase	Not applicable

Assessment
Primary outcomes	The percent change in TKV volumetrically measured by MRI (% per year) will be compared before and after the start of tolvaptan therapy within each patient. The evaluation includes stratified analyses by patient background factors, examination data obtained during the therapy, etc. -Supplementary assessment of the primary outcome variable- Using the "a" as an indicator, the effect of tolvaptan on HtTKV slope will be supplementarily assessed.
Key secondary outcomes	1) The percent change in eGFR (mL/min/1.73 m2 per year) will be compared before and after tolvaptan therapy. The evaluation includes stratified analyses by patient background factors, observation/examination data obtained during the therapy, etc. 2) The safety of tolvaptan will be evaluated. Safety data will be reported to Otsuka Pharmaceutical Co., Ltd., as specified by the protocol. The evaluation includes stratified analyses by patient background factors, examination data obtained during the therapy, etc. 3) Based on the results of 24-hour urine collection, blood tests, inulin clearance, and TKV, the effects of or response to tolvaptan will be evaluated. The evaluation includes stratified analyses by patient background factors, examination data obtained during the therapy, etc. 4) Patients are required to be hospitalized for the first dose of tolvaptan. The results of 24-hour urine collection, and inulin clearance, and other data obtained during the hospitalization will be used to assess the clinical conditions of ADPKD , 5) The correlation between inulin clearance and eGFR estimated using different formulae will be investigated to elucidate the impact of tolvaptan on the correlation. 6) The association between the results of DNA analysis and the effect of tolvaptan will be analyzed.

Base
Study type	Observational

Study design
Basic design
Randomization
Randomization unit
Blinding
Control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms
Purpose of intervention
Type of intervention
Interventions/Control_1
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	18 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1) Patients over the age of 18 who started or will start tolvaptan therapy at Kyorin University Hospital 2) Patients who meet the criteria for the use of Samsca specified by the Ministry of Health, Labour and Welfare - TKV :750 ml or more - TKV slope : approximately 5percent per year or more 3) Patients for whom the TKV and eGFR (percent change) data before the start of tolvaptan therapy are available 4) Patients who freely provided written informed consent to participate in the study
Key exclusion criteria	1) Patients who have been taking tolvaptan since the TEMPO study 2) Patients who are not eligible, at the discretion of Kyorin University Hospital, to take tolvaptan for the stated indication according to the criteria for careful administration of Samsca as specified by the Ministry of Health, Labour and Welfare - Patients with a history of hypersensitivity to tolvaptan or similar chemical compounds - Patients who do not feel thirsty or have difficulty swallowing water - Patients with hypernatremia - Patients with eGFR less than 15 mL/min/1.73 m2 - Patients with chronic hepatitis, drug-induced hepatic dysfunction or other hepatic dysfunctions - Pregnant women or women suspected of being pregnant. Female patients who wish to become pregnant
Target sample size	120

Research contact person
Name of lead principal investigator	1st name Eiji Middle name Last name Higashihara
Organization	Autosomal Dominant Polycystic Kidney Disease Research Section, Kyorin University, School of Medicine
Division name	urology
Zip code	181-8611
Address	6-20-2 Shinkawa, Mitaka, Tokyo 181-8611 Japan
TEL	+81-422-49-7428
Email	ehigashi@ks.kyorin-u.ac.jp

Public contact
Name of contact person	1st name Eiji Middle name Last name Higashihara
Organization	Autosomal Dominant Polycystic Kidney Disease Research Section, Kyorin Univ., School of Med.
Division name	urology
Zip code	181-8611
Address	6-20-2 Shinkawa, Mitaka, Tokyo 181-8611 Japan
TEL	+81-422-49-7428
Homepage URL
Email	ehigashi@ks.kyorin-u.ac.jp

Sponsor
Institute	Autosomal Dominant Polycystic Kidney Disease Research Section, Kyorin University, School of Medicine
Institute
Department

Funding Source
Organization	Otsuka Pharmaceutical Co., Ltd.
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Faculty of Medicine Research Ethics Committee, Kyorin University
Address	6-20-2 Shinkawa, Mitaka, Tokyo 181-8611 Japan
Tel	0422-47-5514
Email	rec@ks.kyorin-u.ac.jp

Secondary IDs
Secondary IDs	YES
Study ID_1	NCT0272966
Org. issuing International ID_1	the U.S. National Institutes of Health, ClinicalTrials.gov
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	杏林大学医学部付属病院(東京都)

Other administrative information
Date of disclosure of the study information	2016 Year 03 Month 12 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled	119
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2016 Year 10 Month 01 Day
Date of IRB	2016 Year 02 Month 25 Day
Anticipated trial start date	2016 Year 10 Month 01 Day
Last follow-up date	2020 Year 08 Month 31 Day
Date of closure to data entry	2020 Year 12 Month 01 Day
Date trial data considered complete	2020 Year 12 Month 02 Day
Date analysis concluded	2020 Year 12 Month 31 Day

Other
Other related information	Percent changes in TKV and eGFR will be compared before and after tolvaptan therapy [Measurements] TKV : At least once per year eGFR : As appropriate 24-hour urine collection : - Once per year (Before tolvaptan therapy) -Twice per year (After tolvaptan therapy) DNA : Once per patient

Management information
Registered date	2016 Year 03 Month 01 Day
Last modified on	2021 Year 03 Month 09 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000024513