Clinical trial NCT02497521: The German ADPKD Tolvaptan Treatment Registry
Official title: The German ADPKD Tolvaptan Treatment Registry is a Prospective, Observational, Multicentric Study of Patients Suffering From ADPKD That Are Considered for Tolvaptan Treatment.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: ADPKD (Autosomal Dominant Polycystic Kidney Disease)
Keywords: polycystic kidney disease
autosomal dominant polycystic kidney disease
ADPKD
Tolvaptan
Jinarc
Lead sponsor: University of Cologne
Sponsor class: OTHER
First posted: 2015-07-14
Enrollment: 2000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with diagnosis of ADPKD and therapy with tolvaptan

Brief summary: The German ADPKD Tolvaptan Treatment Registry is a prospective, observational, multicentric study of patients suffering from ADPKD that are considered for tolvaptan treatment. All ADPKD patients that are evaluated for treatment indication, or that are planned to be treated with tolvaptan, or that are already treated with tolvaptan are eligible. This registry is designed to provide "real-world" data on treatment management of patients with ADPKD.

Detailed description: A substantial number of ADPKD patients treated in our center or referred to our center for counseling are considered eligible for tolvaptan treatment and, thus, will be invited to enter the registry. Furthermore, many patients with ADPKD are treated by nephrologists in practices. We operate a network with many of these practices and will expand this network. Patients can be enrolled - after having obtained approval by the local ethics committee - at external sites (expected number: about 500 patients per year). We are also closely liaised with the German self-help group PKDCure (PKD Familiaere Zystennieren e.V.), which is dedicated to ADPKD-linked research. Recruitment of patients will be facilitated by intensified interacting with these groups. Usually, patients that are referred to our institution for evaluation or counseling are regularly seen once a year. No additional trial-related visits in our institution will be required which is in line with the observational nature of the trial. However, data recording is not restricted to parameters assessed at our center but does include also parameters assessed by the treating physician.

SOPs (Standard Operating Procedures) that include further diagnostic tests like MRI are applied routinely in ADPKD patient management in our institution. The data obtained from these tests will be entered in the registry.

At enrolment, clinical, laboratory data and imaging study findings are collected after obtaining informed consent. The parameters listed below constitute the core data set, additional parameters can be included if considered essential.

Clinical data:

* demographic data (sex, age, height, weight)
* family history
* genotype (if available)
* extrarenal ADPKD manifestations
* co-morbidities
* medication
* physical examination
* blood pressure
* no. of extrarenal and renal complications in the past 12 months (urinary tract infections, pain episodes, macrohematuria, kidney stones, hospital admissions, ...)

Laboratory parameters include primarily (but not exclusively):

* serum sodium
* serum potassium
* serum osmolality
* serum creatinine
* estimated glomerular filtration rate (eGFR)
* serum urea
* serum uric acid
* whole blood count
* liver enzymes, bilirubin
* urinary sodium (spot and 24h-urine)
* urinary potassium
* urinary osmolality
* urinary creatinine
* urinary urea
* urinary uric acid
* urinary protein

Imaging study parameters:

* MRI - TKV (Total Kidney Volume)
* ultrasound
* (CT-scan if available)

Registered patients will be provided with diaries for documentation of tolvaptan dose, adverse side effects etc. These diaries are collected on a yearly basis and the data are included in the registry. Additionally the patients will be asked to fill in a questionnaire regarding the current medication, complications of ADPKD etc. once a year as well as a commercially available SF-12 (quality of life assessment) form.

Data capture will be done at yearly intervals starting at 12 months after enrolment. It includes the biochemical parameters and imaging study findings that have been obtained over the precedent 12 months.

The following additional data will be obtained:

* prescribed tolvaptan dose within the precedent 12 months
* maximum dose of tolvaptan given in the precedent 12 months
* weight, blood pressure
* urine output
* adverse effects
* hospital admissions
* occurrence of kidney pain, haematuria, or urinary tract infection
* complications associated with extrarenal manifestations of ADPKD
* data from diaries and questionnaires as mentioned above

According to the observational character of this study, no additional blood samples, examinations or imaging studies are required per protocol.

Eligibility criteria: Inclusion Criteria:

* Age \> 18 years
* ADPKD proven by positive family history and evidence of renal cysts or diagnosed by treating physician
* Presentation at our center for tolvaptan treatment indication, or tolvaptan treatment planned, or tolvaptan already started

Exclusion Criteria:

* Patients not capable of giving informed consent
* End stage renal disease requiring renal replacement therapy
* Patients receiving tolvaptan as "off-label use"

Primary outcomes:
measure: Drug dosing and titration as a measure of changes in real-life setting
timeFrame: 10 years
measure: Urine osmolarity as a measure of appropriate dosing
timeFrame: 10 years
measure: Evaluation of rate of drug discontinuation and average Duration of therapy
timeFrame: 10 years
Secondary outcomes:
measure: Demographics
timeFrame: 10 years
measure: Clinical and biochemical characteristics at enrolment and treatment initiation
timeFrame: 10 years
measure: Clinical and biochemical characteristics during follow-up
timeFrame: 10 years
measure: Urinary output
timeFrame: 10 years
measure: Evolution of estimated glomerular Filtration rate (eGFR) over the Observation period
timeFrame: 10 years
measure: Evolution of TKV
timeFrame: 10 years
measure: Side effects
timeFrame: 10 years
measure: Liver enzymes
timeFrame: 10 years
Other outcomes:
Locations:
city: Müllheim
country: Germany
facility: Fachinternistische Gemeinschaftspraxis Markgraeferland
state: Baden-Wuerttemberg
city: Wuerzburg
country: Germany
facility: University Hospital of Wuerzburg, ZIM
state: Bayern
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Niedersachsen
city: Cologne
country: Germany
facility: University Hospital of Cologne
state: Nordrhein-Westfalen
city: Nettetal
country: Germany
facility: Nieren- und Diabeteszentrum Nettetal-Lobberich
state: Nordrhein-Westfalen
city: Leipzig
country: Germany
facility: University Hospital of Leipzig, Nephrologische Ambulanz
state: Sachsen
city: Leipzig
country: Germany
facility: Praxisgemeinschaft Dr. Peschel
state: Sachsen
city: Lubeck
country: Germany
facility: University Hospital of Schleswig-Holstein
state: Schleswig-Holstein
city: Lübeck
country: Germany
facility: Nierenzentrum Lübeck
state: Schleswig-Holstein
city: Jena
country: Germany
facility: University Hospital of Jena
state: Thueringen
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus
Study officials:
affiliation: University Hospital of Cologne
name: Thomas Benzing, MD, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Cologne
name: Roman-Ulrich Müller, MD, Prof.
role: PRINCIPAL_INVESTIGATOR
References: