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

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

Sponsors

Lead sponsor: Lisbet Brandi

Source 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.

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.

Overall Status Recruiting
Start Date September 12, 2018
Completion Date April 2020
Primary Completion Date June 2019
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
Change in total Kidney Volume (tKV) measured by MRI scanning Between baseline and six weeks and between six and 12 weeks
Secondary Outcome
Measure Time Frame
Changes in GFR Between baseline and six weeks and between baseline and 12 weeks
Changes in relevant genetic and non-genetic biomarkers associated with CKD and ESRD Between baseline and six weeks and between baseline and 12 weeks
Changes in Quality of Life Between baseline and six weeks and between baseline and 12 weeks
Subject estimation of own health Between baseline and six weeks and between baseline and 12 weeks
Changes in ASAT and ALAT Between baseline and six weeks and between baseline and 12 weeks
Incidence of Adverse Events Between baseline and six weeks and between baseline and 12 weeks
Enrollment 90
Condition
Intervention

Intervention type: Drug

Intervention name: Tolvaptan

Description: 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

Arm group label: Tolvaptan group

Other name: Jinarc

Eligibility

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

Gender: All

Minimum age: 18 Years

Maximum age: 65 Years

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Lisbet Brandi, MD DMSc MHM Principal Investigator KNEA, Nordsjaellands Hospital
Overall Contact

Last name: Lisbet Brandi, MD DMSc MHM

Phone: +45 48295993

Email: [email protected]

Location
facility status contact contact_backup
Aarhus University Hospital - Site 43 | Skejby, Aarhus N, 8200, Denmark Recruiting Henrik Birn, MD +45 6171 7870 [email protected]
Odense University Hospital - Site 45 | Odense, Odense C, 5000, Denmark Not yet recruiting Helle Thiesson, MD +45 6541 1642 [email protected]
Rigshospitalet - Site 42 | Copenhagen, 2100, Denmark Recruiting Bo Feldt-Rasmussen, MD +45 3545 2135 [email protected]
Herlev Hospital | Herlev, 2730, Denmark Recruiting Ditte Hansen, MD +45 3868 2056 [email protected]
Nordsjaellands Hospital - Site 41 | Hillerød, 3400, Denmark Recruiting Lisbet Brandi, MD +45 48295993 [email protected]
Sjællands University Hospital Roskilde | Roskilde, 4000, Denmark Not yet recruiting Bjarne Ørskov, MD +45 2966 2426 [email protected]
Location Countries

Denmark

Verification Date

November 2018

Responsible Party

Responsible party type: Sponsor-Investigator

Investigator affiliation: Nordsjaellands Hospital

Investigator full name: Lisbet Brandi

Investigator title: Head of Department for Endrocrinology and Nephrology, MD, DMSc, MHM

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Tolvaptan group

Arm group type: Active Comparator

Description: Treatment with tolvaptan for six weeks followed by six weeks observation without trial medication

Arm group label: Control group

Arm group type: No Intervention

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

Acronym PoCKET
Study Design Info

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

Primary purpose: Treatment

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

Source: ClinicalTrials.gov