Efficacy of Tolvaptan on ADPKD Patients

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Brief Title

Efficacy of Tolvaptan on ADPKD Patients

Official Title

Longitudinal Efficacy and Safety Study of Tolvaptan on Autosomal Dominant Polycystic Kidney Disease Patients (LET-PKD Study)

Brief Summary

      Investigation of the therapeutic effects of tolvaptan in patients with autosomal dominant
      polycystic kidney disease This is a prospective 5-year study to compare the change in total
      kidney volume (TKV) before and after tolvaptan therapy, as the primary endpoint, in patients
      with ADPKD. Study results will be summarized, analyzed, and compiled into a research paper at
      5 years (data cut-off, Aug 31, 2020).
    

Detailed Description

      Based on the results of a study entitled "The Tolvaptan Efficacy and Safety in Management of
      Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO 3:4) 1)," tolvaptan was
      approved in March 2014 for the treatment of autosomal dominant polycystic Kidney Disease
      (ADPKD) in Japan, followed by in other regions such as Europe and Canada.

      In May 2014, Kyorin University Hospital started administration of tolvaptan to patients with
      ADPKD. In the clinical setting in which the dosing conditions differ from those in the TEMPO
      study, aspects that were not addressed in the TEMPO study may be investigated. The present
      study is a longitudinal clinical study to investigate the changes before and after
      administration of tolvaptan by employing a method different from that used in the TEMPO study
      in patients in whom the clinical course of the disease has been monitored since prior to the
      approval of tolvaptan.

      The observation period (for a maximum duration of 3 years) of the study was originally
      planned to be completed on March 31, 2018 and the analyses of study results and the
      preparation of a research paper until September 2019. However, the study will be extended for
      another 2 years, because the long-term effects of the drug should be further investigated.

      The indication approved in Japan defines the target population as those with an eGFR ≥15
      mL/min/1.73 m2, but not specifies the upper limit of age. Therefore, the present study will
      permit the assessment of therapeutic effects of the drug in patients who are older or have
      more severe renal impairment as compared with in those participating in the TEMPO3:4 and 4.4
      studies. Since such patients generally have a greater TKV, the study may also provide
      information to decide whether the efficacy of tolvaptan differs according to TKV. The present
      study is a single-arm longitudinal study, unlike the preceding studies that were
      placebo-controlled studies 1,2); therefore, tolvaptan may be evaluated from different
      perspectives.

      Rationale of DNA analysis The association between pathogenic genotype and the effects of
      tolvaptan has been reported, but the impact of mutation site has not been cleared 2). Genetic
      analysis for polycystic kidney will be included in the study to decide whether the effects of
      tolvaptan is associated with mutation site as well as pathogenic genotype (PKD1, PKD2).

      Validation of alpha as a HtTKV slope Assuming that TKV corrected for the height at the age at
      measurement (t years old), HtTKVt (mL/m), increases at a constant annual rate (α, %/ per
      year) and the HtTKV0 is 150 mL/m, the following equation will be satisfied: HtTKVt = 150
      (1+α)t. The α value calculated from the equation will be used as an indicator for
      supplementarily assessing the effect of tolvaptan on HtTKV slope 5,6).
    


Study Type

Interventional


Primary Outcome

The percent change in TKV volumetrically

Secondary Outcome

 The percent change in epidermal growth factor receptor (eGER)

Condition

Autosomal Dominant Polycystic Kidney Disease

Intervention

Tolvaptan

Study Arms / Comparison Groups

 Patients with ADPKD
Description:  This analysis set consists of patients whose at least 2 TKV data are available both before and after taking tolvaptan.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

118

Start Date

October 1, 2016

Completion Date

September 30, 2021

Primary Completion Date

August 31, 2020

Eligibility Criteria

        Inclusion Criteria:

          1. Patients who have started or will start receiving tolvaptan at Kyorin University
             Hospital.

          2. Patients whose use of Samsca complies with the criteria specified by the Ministry of
             Health, Labour and Welfare.

               -  TKV ≥ 750 mL.

               -  The increase in total renal capacity ≥ approximately 5%/year.

          3. Patients who have given signed consent to the examination protocol, which includes
             hospitalization at the initiation of tolvaptan treatment (i.e. examination/educational
             hospitalization for the first 3 days. Monthly blood tests at the time of ambulatory
             visits, 24-hour urine collection every 6 months, annual TKV measurement by MRI and
             inulin clearance measurement)

          4. Patients for whom the baseline TKV and eGFR percent change is available.

          5. Patients from whom freely given, written informed consent to participate in the study
             has been obtained.

        Exclusion Criteria:

          1. Patients who do not consent to participation in the study, or those who later withdraw
             their consent.

          2. Patients who have been taking tolvaptan since the TEMPO study.

          3. Patients who are not eligible at our hospital to take tolvaptan for the stated
             indication based on 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 < 15 mL/min/1.73 m2.

               -  Patients with chronic hepatitis, drug-induced hepatic dysfunction and other
                  hepatic dysfunctions.

               -  Pregnant women or women suspected of being pregnant. Female patients who wish to
                  become pregnant.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Eiji Higashihara, MD, , 

Location Countries

Japan

Location Countries

Japan

Administrative Informations


NCT ID

NCT02729662

Organization ID

LET-PKD-1


Responsible Party

Principal Investigator

Study Sponsor

Kyorin University


Study Sponsor

Eiji Higashihara, MD, Principal Investigator, Kyorin University School of Medicine


Verification Date

June 2020