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

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ClinicalTrials.gov Identifier: NCT03596957
Recruitment Status : Recruiting
First Posted : July 24, 2018
Last Update Posted : November 26, 2018
Sponsor:
Information provided by (Responsible Party):
Lisbet Brandi, Nordsjaellands Hospital

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Autosomal Dominant Polycystic Kidney Drug: Tolvaptan Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Patients will be randomised in a 1:1 ration either to treatment with tolvaptan for six weeks followed by six weeks observation without trial medicaion or to the Control group receiving no tolvaptan treatment for 12 weeks
Masking: Single (Outcomes Assessor)
Masking Description: The endpoint blinding will be assured since all the MRI scans will be forwarded to the Comparative Medicine Laboratory in Aarhus for evaluation
Primary Purpose: Treatment
Official Title: Subacute Effect of Tolvaptan on Total Kidney Volume in Adult Patients With Autosomal Dominant Polycystic Kidney Disease
Actual Study Start Date : September 12, 2018
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : April 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases
Drug Information available for: Tolvaptan

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 Name: Jinarc

No Intervention: Control group
No tolvaptan treatment but following the same visit and investigation plan as the subjects in the tolvaptan group



Primary Outcome Measures :
  1. Change in total Kidney Volume (tKV) measured by MRI scanning [ Time Frame: Between baseline and six weeks and between six and 12 weeks ]
    The change in the total Kidney Volume after six and 12 weeks participation in the trial


Secondary Outcome Measures :
  1. Changes in GFR [ Time Frame: Between baseline and six weeks and between baseline and 12 weeks ]
    The changes in GFR measured by Cr-EDTA clearance

  2. Changes in relevant genetic and non-genetic biomarkers associated with CKD and ESRD [ Time Frame: Between baseline and six weeks and between baseline and 12 weeks ]
    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

  3. Changes in Quality of Life [ Time Frame: Between baseline and six weeks and between baseline and 12 weeks ]
    Questionnaire SF36 Health Survey - with 36 questions to subject's health and wellbeing

  4. Subject estimation of own health [ Time Frame: Between baseline and six weeks and between baseline and 12 weeks ]
    Estimated by a Visual Analogue Scale from 0 (worth wellbeing) to 100 (best wellbeing

  5. Changes in ASAT and ALAT [ Time Frame: Between baseline and six weeks and between baseline and 12 weeks ]
    Changes estimated from laboratory results

  6. Incidence of Adverse Events [ Time Frame: Between baseline and six weeks and between baseline and 12 weeks ]
    Evaluation of Adverse Events including severity, causality, outcome and seriousness assessments



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03596957


Contacts
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Contact: Lisbet Brandi, MD DMSc MHM +45 48295993 lisbet.brandi@regionh.dk
Contact: Clinical Project Manager +45 48294714 charlotte.bjernved.nielsen@regionh.dk

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

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Responsible Party: Lisbet Brandi, Head of Department for Endrocrinology and Nephrology, MD, DMSc, MHM, Nordsjaellands Hospital
ClinicalTrials.gov Identifier: NCT03596957     History of Changes
Other Study ID Numbers: PoCKET
First Posted: July 24, 2018    Key Record Dates
Last Update Posted: November 26, 2018
Last Verified: November 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Kidney Diseases
Polycystic Kidney Diseases
Polycystic Kidney, Autosomal Dominant
Urologic Diseases
Kidney Diseases, Cystic
Abnormalities, Multiple
Congenital Abnormalities
Ciliopathies
Genetic Diseases, Inborn
Tolvaptan
Antidiuretic Hormone Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Physiological Effects of Drugs