Subacute Effect of Tolvaptan on Total Kidney Volume in Adult Patients With Autosomal Dominant Polycystic Kidney Disease
Trial Snapshot
- Phase
- Phase 4
- Sponsor
- Enrollment
- 90
- Locations
- 6
- Primary Endpoint
- Change in total Kidney Volume (tKV) measured by MRI scanning
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- 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
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Tolvaptan group
Treatment with tolvaptan for six weeks followed by six weeks observation without trial medication
Intervention: Tolvaptan (Drug)
Outcomes
Primary Outcomes
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 Outcomes
- Changes in ASAT and ALAT(Between baseline and six weeks and between baseline and 12 weeks)
- 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)
- Incidence of Adverse Events(Between baseline and six weeks and between baseline and 12 weeks)
Investigators
Lisbet Brandi
Head of Department for Endrocrinology and Nephrology, MD, DMSc, MHM
Nordsjaellands Hospital