Pulsed Oral Sirolimus in Autosomal Dominant Polycystic Kidney Disease (RAP)
Primary Purpose
Polycystic Kidney, Type 1 Autosomal Dominant Disease, Polycystic Kidney, Type 2 Autosomal Dominant Disease
Status
Unknown status
Phase
Phase 3
Locations
Austria
Study Type
Interventional
Intervention
Sirolimus
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Polycystic Kidney, Type 1 Autosomal Dominant Disease focused on measuring ADPKD, PKD, Polycystic kidney disease, Mammalian target of rapamycin, mTOR-I, Sirolimus
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- Concomitant glomerular diseases
- Psychiatric disorders and any condition that might prevent full comprehension of the purposes and risks of the study
- History of malignancy, with the exception of adequately treated basal cell- and squamous cell carcinoma of the skin
- HIV positivity
Sites / Locations
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of ViennaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Sirolimus
Placebo
Arm Description
Fixed oral dose of 3 mg Sirolimus (blinded) once weekly for 24 months.
Fixed oral dose of placebo (blinded) once weekly for 24 months.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Change of safety parameters from baseline to month 24
Safety, change in proteinuria, as indicated by albumin/creatinine- and protein/creatinine ratio, respectively.
Full Information
NCT ID
NCT02055079
First Posted
January 31, 2014
Last Updated
October 30, 2018
Sponsor
Medical University of Vienna
1. Study Identification
Unique Protocol Identification Number
NCT02055079
Brief Title
Pulsed Oral Sirolimus in Autosomal Dominant Polycystic Kidney Disease
Acronym
RAP
Official Title
Pulsed Oral Sirolimus in Autosomal Dominant Polycystic Kidney Disease - The Vienna RAP Study
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Unknown status
Study Start Date
April 2014 (undefined)
Primary Completion Date
April 2019 (Anticipated)
Study Completion Date
December 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical University of Vienna
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycystic Kidney, Type 1 Autosomal Dominant Disease, Polycystic Kidney, Type 2 Autosomal Dominant Disease
Keywords
ADPKD, PKD, Polycystic kidney disease, Mammalian target of rapamycin, mTOR-I, Sirolimus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
68 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Sirolimus
Arm Type
Experimental
Arm Description
Fixed oral dose of 3 mg Sirolimus (blinded) once weekly for 24 months.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Fixed oral dose of placebo (blinded) once weekly for 24 months.
Intervention Type
Drug
Intervention Name(s)
Sirolimus
Other Intervention Name(s)
Rapamune
Intervention Description
Fixed oral dose of 3 mg sirolimus (blinded) once weekly for 24 months.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Fixed oral dose of 3 mg placebo (blinded) once weekly for 24 months.
Primary Outcome Measure Information:
Title
Change in kidney function from baseline to month 24
Description
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.
Time Frame
Baseline, 24 months
Secondary Outcome Measure Information:
Title
Change of safety parameters from baseline to month 24
Description
Safety, change in proteinuria, as indicated by albumin/creatinine- and protein/creatinine ratio, respectively.
Time Frame
Baseline, 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Concomitant glomerular diseases
Psychiatric disorders and any condition that might prevent full comprehension of the purposes and risks of the study
History of malignancy, with the exception of adequately treated basal cell- and squamous cell carcinoma of the skin
HIV positivity
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Markus Riegersperger, MD
Phone
0043140400
Ext
4391
Email
markus.riegersperger@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Gere Sunder-Plassmann, MD
Phone
0043140400
Ext
4391
Email
gere.sunder-plassmann@meduniwien.ac.at
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Markus Riegersperger, MD
Organizational Affiliation
Medical University of Vienna
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Gere Sunder-Plassmann, MD
Organizational Affiliation
Medical University of Vienna
Official's Role
Principal Investigator
Facility Information:
Facility Name
Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Markus Riegersperger, MD
Phone
0043140400
Ext
4391
Email
markus.riegersperger@gmail.com
First Name & Middle Initial & Last Name & Degree
Gere Sunder-Plassmann, MD
Phone
0043140400
Ext
4391
Email
gere.sunder-plassmann@meduniwien.ac.at
First Name & Middle Initial & Last Name & Degree
Markus Riegersperger, MD
First Name & Middle Initial & Last Name & Degree
Gere Sunder-Plassmann, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
25899445
Citation
Riegersperger 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.
Results Reference
derived
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Pulsed Oral Sirolimus in Autosomal Dominant Polycystic Kidney Disease
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