Efficacy of Tolvaptan on ADPKD Patients

NCT02729662 | Unknown DMC

• 1 other identifier: LET-PKD-1
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 1

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).

Conditions

Autosomal Dominant Polycystic Kidney Disease

Outcome Measures

Primary Outcomes (1)

• The percent change in TKV volumetrically

  To evaluate the efficacy, the percent change in TKV volumetrically measured by MRI (% per year) is to be compared before and after administering tolvaptan to the same patients. The evaluation will include stratified analyses by patient background variables and examination data obtained during treatment. \[Supplementary assessment of the primary outcome variable\] Using HtTKV slope, α (% per year), calculated from the HtTKVt at t years old as an indicator, the effect of tolvaptan on HtTKV slope will be supplementarily assessed 5,6).

  once a year, up to study completion, an expected average of up to 5 years

Secondary Outcomes (5)

• The percent change in epidermal growth factor receptor (eGER)

  once a month, up to study completion, an expected average of up to 5 years

• A number of adverse events during the study

  through study completion, an expected average of up to 5 years

• The efficacy of or response to tolvaptan will be evaluated.

  twice a year, up to study completion, an expected average of up to5 years

• The impact of tolvaptan on the correlation between inulin clearance and eGFR values

  once a month, up to study completion, an expected average of up to 5 months

• The association between the result of DNA analysis and the effect of tolvaptan

  through study completion, an expected average of up to 5 years

Study Arms (1)

Patients with ADPKD

OTHER

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

Drug: Tolvaptan

Interventions

Tolvaptan DRUG

* Before administration of tolvaptan * TKV・Liver capacity: Once/year (an additional measurement within 3 months before start of administration) * 24-hour urine collection・Hematology/urinalysis: Once/year * Physical findings: Blood pressure and medical interview at ambulatory visit * Hospitalization for education and examination at the start of tolvaptan administration * 24-hour urine collection・Hematology/urinalysis・Inulin clearance * Physical findings: Body weight, blood pressure * Adverse Events * After administration of tolvaptan * TKV・Liver capacity・inulin clearance: Once/year * 24-hour urine collection: Once/6 months * Hematology/urinalysis: Once/month in principle * Physical findings: Blood pressure and medical interview at ambulatory visit * Adverse Events

Also known as: Samsca

Patients with ADPKD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who have started or will start receiving tolvaptan at Kyorin University Hospital.
• 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.
• 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)
• Patients for whom the baseline TKV and eGFR percent change is available.
• Patients from whom freely given, written informed consent to participate in the study has been obtained.

You may not qualify if:

• Patients who do not consent to participation in the study, or those who later withdraw their consent.
• Patients who have been taking tolvaptan since the TEMPO study.
• 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.

Sponsors & Collaborators

• Kyorin University: lead

Study Sites (1)

Kyorin University Hospital

Mitaka, Tokyo, 181-8611, Japan

Location

Related Publications (11)

• Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Grantham JJ, Higashihara E, Perrone RD, Krasa HB, Ouyang J, Czerwiec FS; TEMPO 3:4 Trial Investigators. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2012 Dec 20;367(25):2407-18. doi: 10.1056/NEJMoa1205511. Epub 2012 Nov 3.

  PMID: 23121377 BACKGROUND

• Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Perrone RD, Dandurand A, Ouyang J, Czerwiec FS, Blais JD; TEMPO 4:4 Trial Investigators. Multicenter, open-label, extension trial to evaluate the long-term efficacy and safety of early versus delayed treatment with tolvaptan in autosomal dominant polycystic kidney disease: the TEMPO 4:4 Trial. Nephrol Dial Transplant. 2017 Jul 1;32(7):1262. doi: 10.1093/ndt/gfx079. No abstract available.

  PMID: 28444221 BACKGROUND

• Higashihara E, Nutahara K, Okegawa T, Shishido T, Tanbo M, Kobayasi K, Nitadori T. Kidney volume and function in autosomal dominant polycystic kidney disease. Clin Exp Nephrol. 2014 Feb;18(1):157-65. doi: 10.1007/s10157-013-0834-4. Epub 2013 Jul 18.

  PMID: 23864346 BACKGROUND

• Higashihara E, Nutahara K, Okegawa T, Tanbo M, Hara H, Miyazaki I, Kobayasi K, Nitatori T. Kidney volume estimations with ellipsoid equations by magnetic resonance imaging in autosomal dominant polycystic kidney disease. Nephron. 2015;129(4):253-62. doi: 10.1159/000381476. Epub 2015 Apr 16.

  PMID: 25895545 BACKGROUND

• Irazabal MV, Rangel LJ, Bergstralh EJ, Osborn SL, Harmon AJ, Sundsbak JL, Bae KT, Chapman AB, Grantham JJ, Mrug M, Hogan MC, El-Zoghby ZM, Harris PC, Erickson BJ, King BF, Torres VE; CRISP Investigators. Imaging classification of autosomal dominant polycystic kidney disease: a simple model for selecting patients for clinical trials. J Am Soc Nephrol. 2015 Jan;26(1):160-72. doi: 10.1681/ASN.2013101138. Epub 2014 Jun 5.

  PMID: 24904092 BACKGROUND

• Girardat-Rotar L, Braun J, Puhan MA, Abraham AG, Serra AL. Temporal and geographical external validation study and extension of the Mayo Clinic prediction model to predict eGFR in the younger population of Swiss ADPKD patients. BMC Nephrol. 2017 Jul 17;18(1):241. doi: 10.1186/s12882-017-0654-y.

  PMID: 28716055 BACKGROUND

• Kinoshita M, Higashihara E, Kawano H, Higashiyama R, Koga D, Fukui T, Gondo N, Oka T, Kawahara K, Rigo K, Hague T, Katsuragi K, Sudo K, Takeshi M, Horie S, Nutahara K. Technical Evaluation: Identification of Pathogenic Mutations in PKD1 and PKD2 in Patients with Autosomal Dominant Polycystic Kidney Disease by Next-Generation Sequencing and Use of a Comprehensive New Classification System. PLoS One. 2016 Nov 11;11(11):e0166288. doi: 10.1371/journal.pone.0166288. eCollection 2016.

  PMID: 27835667 BACKGROUND

• Higashihara E, Horie S, Kinoshita M, Harris PC, Okegawa T, Tanbo M, Hara H, Yamaguchi T, Shigemori K, Kawano H, Miyazaki I, Kaname S, Nutahara K. A potentially crucial role of the PKD1 C-terminal tail in renal prognosis. Clin Exp Nephrol. 2018 Apr;22(2):395-404. doi: 10.1007/s10157-017-1477-7. Epub 2017 Oct 5.

  PMID: 28983800 BACKGROUND

• Tan AY, Michaeel A, Liu G, Elemento O, Blumenfeld J, Donahue S, Parker T, Levine D, Rennert H. Molecular diagnosis of autosomal dominant polycystic kidney disease using next-generation sequencing. J Mol Diagn. 2014 Mar;16(2):216-28. doi: 10.1016/j.jmoldx.2013.10.005. Epub 2013 Dec 27.

  PMID: 24374109 BACKGROUND

• Irazabal MV, Torres VE, Hogan MC, Glockner J, King BF, Ofstie TG, Krasa HB, Ouyang J, Czerwiec FS. Short-term effects of tolvaptan on renal function and volume in patients with autosomal dominant polycystic kidney disease. Kidney Int. 2011 Aug;80(3):295-301. doi: 10.1038/ki.2011.119. Epub 2011 May 4.

  PMID: 21544064 BACKGROUND

• Boertien WE, Meijer E, de Jong PE, Bakker SJ, Czerwiec FS, Struck J, Oberdhan D, Shoaf SE, Krasa HB, Gansevoort RT. Short-term renal hemodynamic effects of tolvaptan in subjects with autosomal dominant polycystic kidney disease at various stages of chronic kidney disease. Kidney Int. 2013 Dec;84(6):1278-86. doi: 10.1038/ki.2013.285. Epub 2013 Jul 31.

  PMID: 23903369 BACKGROUND

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant

Interventions

Tolvaptan

Condition Hierarchy (Ancestors)

Polycystic Kidney Diseases; Kidney Diseases, Cystic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ciliopathies; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Eiji Higashihara, MD

  Kyorin University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Adjunct Professor

Study Record Dates

• First Submitted: March 11, 2016
• First Posted: April 6, 2016
• Study Start: October 1, 2016
• Primary Completion: August 31, 2020
• Study Completion: September 30, 2021
• Last Updated: June 5, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)