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

Autosomal Dominant Polycystic Kidney Clinical Trial

— PoCKET  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03596957
• Other study ID #: PoCKET
• Status: Recruiting
• Phase: Phase 4
• Start date: September 12, 2018
• Est. completion date: April 2020

Study information

• Verified date: November 2018
• Source: Nordsjaellands Hospital
• Contact: Lisbet Brandi, MD DMSc MHM
• Phone: +45 48295993
• Email: lisbet.brandi[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: April 2020
• Est. primary completion date: June 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Autosomal Dominant Polycystic Kidney
• Kidney Diseases
• Polycystic Kidney Diseases
• Polycystic Kidney, Autosomal Dominant

Intervention

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

Locations

Country	Name	City	State
Denmark	Rigshospitalet - Site 42	Copenhagen
Denmark	Herlev Hospital	Herlev
Denmark	Nordsjaellands Hospital - Site 41	Hillerød
Denmark	Odense University Hospital - Site 45	Odense	Odense C
Denmark	Sjællands University Hospital Roskilde	Roskilde
Denmark	Aarhus University Hospital - Site 43	Skejby	Aarhus N

Sponsors (1)

Lead Sponsor	Collaborator
Lisbet Brandi

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Changes in GFR	The changes in GFR measured by Cr-EDTA clearance	Between baseline and six weeks and between baseline and 12 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	Changes in ASAT and ALAT	Changes estimated from laboratory results	Between baseline and six weeks and between baseline and 12 weeks
Secondary	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