Clinical trial NCT03596957: Subacute Effect of Tolvaptan on Total Kidney Volume in Adult Patients With Autosomal Dominant Polycystic Kidney Disease
Official title: Subacute Effect of Tolvaptan on Total Kidney Volume in Adult Patients With Autosomal Dominant Polycystic Kidney Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Autosomal Dominant Polycystic Kidney
Lead sponsor: Nordsjaellands Hospital
Sponsor class: OTHER
First posted: 2018-07-24
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

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.

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

Primary outcomes:
measure: Change in total Kidney Volume (tKV) measured by MRI scanning
timeFrame: Between baseline and six weeks and between six and 12 weeks
Secondary outcomes:
measure: Changes in GFR
timeFrame: Between baseline and six weeks and between baseline and 12 weeks
measure: Changes in relevant genetic and non-genetic biomarkers associated with CKD and ESRD
timeFrame: Between baseline and six weeks and between baseline and 12 weeks
measure: Changes in Quality of Life
timeFrame: Between baseline and six weeks and between baseline and 12 weeks
measure: Subject estimation of own health
timeFrame: Between baseline and six weeks and between baseline and 12 weeks
measure: Changes in ASAT and ALAT
timeFrame: Between baseline and six weeks and between baseline and 12 weeks
measure: Incidence of Adverse Events
timeFrame: Between baseline and six weeks and between baseline and 12 weeks
Other outcomes:
Locations:
city: Skejby
country: Denmark
facility: Aarhus University Hospital - Site 43
state: Aarhus N
city: Odense
country: Denmark
facility: Odense University Hospital - Site 45
state: Odense C
city: Copenhagen
country: Denmark
facility: Rigshospitalet - Site 42
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Hillerød
country: Denmark
facility: Nordsjaellands Hospital - Site 41
city: Roskilde
country: Denmark
facility: Sjællands University Hospital Roskilde
Study officials:
affiliation: KNEA, Nordsjaellands Hospital
name: Lisbet Brandi, MD DMSc MHM
role: PRINCIPAL_INVESTIGATOR
References: