Subacute Effect of Tolvaptan on Total Kidney Volume in Adult Patients With Autosomal Dominant Polycystic Kidney Disease (PoCKET)

Investigator initiated controlled multi-centre trial in a Prospective, Randomised, Open, Blinded Endpoint (PROBE) design.

Patients will be randomised in a 1:1 ratio either to treatment with tolvaptan for six weeks followed by six weeks observation without trial medication or no tolvaptan treatment, but following the same visit and investigation plan as the subjects taking tolvaptan.

Study Overview

• Status: Unknown
• Conditions: Autosomal Dominant Polycystic Kidney
• Intervention / Treatment: Drug: Tolvaptan

Detailed Description

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common genetic kidney disease and the fourth leading cause of end-stage renal disease in adults Worldwide.

The tolvaptan tablet has been approved by EMA (European Medicines Agency) with the indication of slowing the progression of cysts development and renal insufficiency in adults with ADPKD. It is the newest and only possible treatment for this patient group and could be initiated in patients with evidence for rapidly progressive disease Development.

There is however in Denmark and other countries both scientific and financial reluctance to initiate this expensive treatment for several reasons e.g. selection of patients who might benefit, effect on progression of kidney disease, side effects and tolerability.

Before deciding on implementation in Denmark, more knowledge is needed. The results of the PoCKET trial will contribute with guidance on this decision.

Foremost the trial is designed to address not only the change in kidney volume, but the change in kidney function, which is what matters to the patients and their prognosis in terms of postponing time to end stage renal disease. Furthermore, important data on side effects and tolerability will be generated.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Rigshospitalet - Site 42
    • Contact: Bo Feldt-Rasmussen, MD; Phone Number: +45 3545 2135; Email: Bo.Feldt-Rasmussen@regionh.dk
    • Contact: Tobias Bomholt, MD; Phone Number: +45 35451838; Email: tobias.bomholt@regionh.dk
  • Herlev, Denmark, 2730
    • Recruiting
    • Herlev Hospital
    • Contact: Ditte Hansen, MD; Phone Number: +45 3868 2056; Email: ditte.hansen@regionh.dk
    • Contact: Marie Moeller, MD; Phone Number: +45 6169 5364; Email: marie.moeller@regioh.dk
  • Hillerød, Denmark, 3400
    • Recruiting
    • Nordsjaellands Hospital - Site 41
    • Contact: Lisbet Brandi, MD; Phone Number: +45 48295993; Email: lisbet.brandi@regionh.dk
    • Contact: Charlotte Bjernved Nielsen; Phone Number: +45 49294714; Email: charlotte.bjernved.nielsen@regionh.dk
  • Roskilde, Denmark, 4000
    • Not yet recruiting
    • Sjællands University Hospital Roskilde
    • Contact: Bjarne Ørskov, MD; Phone Number: +45 2966 2426; Email: bjaoe@regionsjalelland.dk
  • Aarhus N
    • Skejby, Aarhus N, Denmark, 8200
      • Recruiting
      • Aarhus University Hospital - Site 43
      • Contact: Henrik Birn, MD; Phone Number: +45 6171 7870; Email: hb@biomed.au.dk
      • Contact: Karin Hansen; Phone Number: +45 4046 0831; Email: Karin.hansen@skejby.rm.dk
  • Odense C
    • Odense, Odense C, Denmark, 5000
      • Not yet recruiting
      • Odense University Hospital - Site 45
      • Contact: Helle Thiesson, MD; Phone Number: +45 6541 1642; Email: helle.thiesson@rsyd.dk
      • Contact: Kristian Bergholt Buhl, MD; Phone Number: +456541 1642; Email: kristian.bergholt.buhl@rsyd.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients between 18 and 65 years
• Diagnosis of typical ADPKD
• tKV above or equal to 750 ml by MRI scanning
• Estimated GFR (e-GFR) by CKD-EPI formula of above or equal to 45 mL/min/1.73 m2

Exclusion Criteria:

• Kidney transplant recipient
• Known liver disease except for liver cysts relating to ADPKD
• ASAT and ALAT above upper normal level
• Current treatment with thiazide and thiazide-line diuretics, mineral corticoid receptor antagonists, amiloride or loop diuretics
• Evidence of urinary tract obstruction
• Current treatment with CYP3A4 inhibitors
• Active malignant disease
• Current or previous treatment with tolvaptan

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Tolvaptan group; Treatment with tolvaptan for six weeks followed by six weeks observation without trial medication	Drug: Tolvaptan; At baseline the tolvaptan dosing will start with daily morning and afternoon doses of 45 mg and 15 mg respectively, with weekly increases to 60 mg and 30 mg and then to 90 mg and 30 mg according to subject tolerability; Other Names: Jinarc
NO_INTERVENTION: Control group; No tolvaptan treatment but following the same visit and investigation plan as the subjects in the tolvaptan group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in total Kidney Volume (tKV) measured by MRI scanning	The change in the total Kidney Volume after six and 12 weeks participation in the trial	Between baseline and six weeks and between six and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in GFR	The changes in GFR measured by Cr-EDTA clearance	Between baseline and six weeks and between baseline and 12 weeks
Changes in relevant genetic and non-genetic biomarkers associated with CKD and ESRD	Prediction of change in progression of the disease over time in the genes PKD1, PKD2, PKHD1 and HNF1B. The following biomarkers will be determined: NGAL, UMOD, MCP-1, KIM-1, cystatin-C and copeptin	Between baseline and six weeks and between baseline and 12 weeks
Changes in Quality of Life	Questionnaire SF36 Health Survey - with 36 questions to subject's health and wellbeing	Between baseline and six weeks and between baseline and 12 weeks
Subject estimation of own health	Estimated by a Visual Analogue Scale from 0 (worth wellbeing) to 100 (best wellbeing	Between baseline and six weeks and between baseline and 12 weeks
Changes in ASAT and ALAT	Changes estimated from laboratory results	Between baseline and six weeks and between baseline and 12 weeks
Incidence of Adverse Events	Evaluation of Adverse Events including severity, causality, outcome and seriousness assessments	Between baseline and six weeks and between baseline and 12 weeks

Collaborators and Investigators

• Sponsor: Lisbet Brandi
• Investigators: Principal Investigator: Lisbet Brandi, MD DMSc MHM, KNEA, Nordsjaellands Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 12, 2018
• Primary Completion (ANTICIPATED): June 1, 2019
• Study Completion (ANTICIPATED): April 1, 2020

Study Registration Dates

• First Submitted: February 14, 2018
• First Submitted That Met QC Criteria: July 13, 2018
• First Posted (ACTUAL): July 24, 2018

Study Record Updates

• Last Update Posted (ACTUAL): November 26, 2018
• Last Update Submitted That Met QC Criteria: November 22, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Musculoskeletal Abnormalities; Abnormalities, Multiple; Kidney Diseases, Cystic; Ciliopathies; Kidney Diseases; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant; Arthrogryposis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Antidiuretic Hormone Receptor Antagonists; Tolvaptan
• Other Study ID Numbers: POCKET

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No