Pulsed Oral Sirolimus in Autosomal Dominant Polycystic Kidney Disease
RAP
4 other identifiers
interventional
68
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Apr 2014
Longer than P75 for phase_3
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 31, 2014
CompletedFirst Posted
Study publicly available on registry
February 4, 2014
CompletedStudy Start
First participant enrolled
April 1, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2019
CompletedOctober 31, 2018
October 1, 2018
5 years
January 31, 2014
October 30, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change in kidney function from baseline to month 24
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.
Baseline, 24 months
Secondary Outcomes (1)
Change of safety parameters from baseline to month 24
Baseline, 24 months
Study Arms (2)
Sirolimus
EXPERIMENTALFixed oral dose of 3 mg Sirolimus (blinded) once weekly for 24 months.
Placebo
PLACEBO COMPARATORFixed oral dose of placebo (blinded) once weekly for 24 months.
Interventions
Eligibility Criteria
You may qualify if:
- ADPKD, as confirmed by history, ultrasound, computed- or magnetic resonance tomography
- Eighteen years of age, or older
- Baseline eGFR below 60 mL/min per 1.73m2
- Negative serum pregnancy test prior to administration of sirolimus and agreement to use contraception throughout the study and three months after
- Written informed consent
You may not qualify if:
- Need for renal replacement therapy
- Pregnancy/lactation
- Plans to become pregnant in the near future
- Refusal to use sufficient contraception
- Proteinuria as defined as protein:creatinine ratio \>1000 or \>1g/d, respectively
- History of life threatening complications of ADPKD
- Evidence of active systemic- or localized major infection
- Evidence of infiltrate or consolidation on chest X-ray
- Use of any investigational drug or -treatment up to 4 weeks prior to enrolment and during the study
- Known allergy/hypersensitivity to sirolimus and its derivatives
- Medication that will interfere with the cytochrome P450 (CYP3A4/CYP3A5) system
- Total white blood cell count below or equal to 3000/mm3
- Platelet count below or equal to 100.000/mm3
- Fasting triglycerides above or equal to 400 mg/dL
- Fasting total cholesterol above or equal to 300 mg/dL
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna
Vienna, 1090, Austria
Related Publications (2)
St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.
PMID: 39356039DERIVEDRiegersperger M, Herkner H, Sunder-Plassmann G. Pulsed oral sirolimus in advanced autosomal-dominant polycystic kidney disease (Vienna RAP Study): study protocol for a randomized controlled trial. Trials. 2015 Apr 23;16:182. doi: 10.1186/s13063-015-0692-3.
PMID: 25899445DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Markus Riegersperger, MD
Medical University of Vienna
- PRINCIPAL INVESTIGATOR
Gere Sunder-Plassmann, MD
Medical University of Vienna
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Dr.
Study Record Dates
First Submitted
January 31, 2014
First Posted
February 4, 2014
Study Start
April 1, 2014
Primary Completion
April 1, 2019
Study Completion
December 1, 2019
Last Updated
October 31, 2018
Record last verified: 2018-10
Data Sharing
- IPD Sharing
- Will not share