Pulsed Oral Sirolimus in Autosomal Dominant Polycystic Kidney Disease (RAP)
Sirolimus (SIR) has lead to a reduction of overall kidney size, a decrease in cyst density and general tubular cell proliferation in animal models, and to a reduction of the increase in creatinine and blood urea nitrogen by 34 and 39 percent respectively, as well as a reduction of cyst proliferation, expressed by a 30 percent reduction of overall kidney enlargement, a reduction in general cyst volume, and a reduction of the cyst volume density in the renal cortex in humans.
However, despite promising data from animal- and in vivo studies, most mammalian target of rapamycin inhibitor (mTOR-I) studies in patients with autosomal-dominant polycystic kidney disease (ADPKD) produced only subtle if any clinically relevant effects on cyst growth and the preservation of renal function.
In this study we will investigate if pulsed administration of SIR in a fixed weekly oral dose of 3 mg over 24 months compared to placebo significantly reduces cyst growth and preserves excretory renal function in patients with ADPKD and an estimated glomerular filtration (eGFR) rate below 60 mL/min per 1.73m2.
|Polycystic Kidney, Type 1 Autosomal Dominant Disease Polycystic Kidney, Type 2 Autosomal Dominant Disease||Drug: Sirolimus Drug: Placebo||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Pulsed Oral Sirolimus in Autosomal Dominant Polycystic Kidney Disease - The Vienna RAP Study|
- Change in kidney function from baseline to month 24 [ Time Frame: Baseline, 24 months ]Fifty percent reduction in doubling of serum creatinine, or initiation of dialysis over a period of two years. Less or equal than 1.5 fold increase in serum creatinine without initiation of dialysis over two years is considered a beneficial outcome, increases in serum creatinine greater than 1.5 over two years or initiation of dialysis are considered a non-beneficial outcome.
- Change of safety parameters from baseline to month 24 [ Time Frame: Baseline, 24 months ]Safety, change in proteinuria, as indicated by albumin/creatinine- and protein/creatinine ratio, respectively.
|Study Start Date:||April 2014|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||April 2017 (Final data collection date for primary outcome measure)|
Fixed oral dose of 3 mg Sirolimus (blinded) once weekly for 24 months.
Fixed oral dose of 3 mg sirolimus (blinded) once weekly for 24 months.
Other Name: Rapamune
Placebo Comparator: Placebo
Fixed oral dose of placebo (blinded) once weekly for 24 months.
Fixed oral dose of 3 mg placebo (blinded) once weekly for 24 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02055079
|Contact: Markus Riegersperger, MD||0043140400 ext firstname.lastname@example.org|
|Contact: Gere Sunder-Plassmann, MD||0043140400 ext email@example.com|
|Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna||Recruiting|
|Vienna, Austria, 1090|
|Contact: Markus Riegersperger, MD 0043140400 ext 4391 firstname.lastname@example.org|
|Contact: Gere Sunder-Plassmann, MD 0043140400 ext 4391 email@example.com|
|Principal Investigator: Markus Riegersperger, MD|
|Sub-Investigator: Gere Sunder-Plassmann, MD|
|Principal Investigator:||Markus Riegersperger, MD||Medical University of Vienna|
|Principal Investigator:||Gere Sunder-Plassmann, MD||Medical University of Vienna|