Polycystic Kidney, Type 1 Autosomal Dominant DiseasePhase 3RAPNCT02055079
Pulsed Oral Sirolimus in Autosomal Dominant Polycystic Kidney Disease
A Phase 3 study testing Sirolimus in people with Polycystic Kidney, Type 1 Autosomal Dominant Disease and Polycystic Kidney, Type 2 Autosomal Dominant Disease, run by Medical University of Vienna at 1 site in Austria.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Polycystic Kidney, Type 1 Autosomal Dominant Disease, Polycystic Kidney, Type 2 Autosomal Dominant Disease
- What is being tested?
- Sirolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 68 participants
- Where
- 1 siteAustria
- Study dates
- Apr 2014to Dec 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Austria1 site, 1 recruiting
- Recruiting
Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna
Vienna, 1090
Markus Riegersperger, MD, 0043140400 ext. 4391, markus.riegersperger@gmail.com
Gere Sunder-Plassmann, MD, 0043140400 ext. 4391, gere.sunder-plassmann@meduniwien.ac.at
About this study
Official title: Pulsed Oral Sirolimus in Autosomal Dominant Polycystic Kidney Disease - The Vienna RAP Study
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.
- Conditions
- Polycystic Kidney, Type 1 Autosomal Dominant Disease, Polycystic Kidney, Type 2 Autosomal Dominant Disease
- Being tested
- Sirolimus, Placebo
- Keywords
- ADPKD, PKD, Polycystic kidney disease, Mammalian target of rapamycin, mTOR-I, Sirolimus
- Medical subject headings
- Polycystic Kidney, Autosomal Dominant, Polycystic Kidney Diseases, Hereditary Sensory and Autonomic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Also called Rapamune
Fixed oral dose of 3 mg sirolimus (blinded) once weekly for 24 months.
PlaceboDrug
Fixed oral dose of 3 mg placebo (blinded) once weekly for 24 months.
| Study group | Role | What they receive |
|---|---|---|
| Sirolimus | Experimental | Fixed oral dose of 3 mg Sirolimus (blinded) once weekly for 24 months. Receives: Drug: Sirolimus |
| Placebo | Placebo comparator | Fixed oral dose of placebo (blinded) once weekly for 24 months. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, 24 months
Secondary outcomes (1)
Change of safety parameters from baseline to month 24
Safety, change in proteinuria, as indicated by albumin/creatinine- and protein/creatinine ratio, respectively.
Measured: Baseline, 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2014 (estimated)
- Study startApr 2014
- Primary completionApr 2019 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Polycystic Kidney, Type 1 Autosomal Dominant DiseaseStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 68 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Markus Riegersperger, MD, Medical University of Vienna
- Investigators
- Markus Riegersperger, MD, Principal investigator, Medical University of ViennaGere Sunder-Plassmann, MD, Principal investigator, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02055079
- Sponsor's protocol ID
- V5.1/20.1.2013
- Other IDs
- 2012-000550-60, 15170, 1060/2012
- Acronym
- RAP
- Status last verified
- Oct 2018
- First submitted
- 31 Jan 2014
- Last updated
- 31 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 39356039Riegersperger 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.
PubMed 25899445
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pulsed Oral Sirolimus in Autosomal Dominant Polycystic Kidney Disease - The Vienna RAP Study
- ClinicalTrials.gov ID
- NCT02055079
- Acronym / sponsor ID
- RAP / V5.1/20.1.2013
- Conditions
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 68 participants (estimated)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- Apr 2014
- Primary completion
- Apr 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 4 Feb 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sirolimus | Experimental | Drug: SirolimusFixed oral dose of 3 mg Sirolimus (blinded) once weekly for 24 months. |
| Placebo | Placebo comparator | Drug: PlaceboFixed oral dose of placebo (blinded) once weekly for 24 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SirolimusAlso: RapamuneFixed oral dose of 3 mg sirolimus (blinded) once weekly for 24 months. | Drug | Sirolimus |
| PlaceboFixed oral dose of 3 mg placebo (blinded) once weekly for 24 months. | Drug | Placebo |
Primary outcome
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.
1 secondary outcome
Change of safety parameters from baseline to month 24
Time frame: Baseline, 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2018.
- Derived from this study: PubMed 39356039St 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.
- Derived from this study: PubMed 25899445Riegersperger 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Markus Riegersperger, MD principal investigator
Medical University of Vienna
Gere Sunder-Plassmann, MD principal investigator
Medical University of Vienna
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sirolimus in people with Polycystic Kidney, Type 1 Autosomal Dominant Disease and Polycystic Kidney, Type 2 Autosomal Dominant Disease, run by Medical University of Vienna at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 31 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Markus Riegersperger, MD (0043140400 ext. 4391, markus.riegersperger@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in kidney function from baseline to month 24 (time frame: Baseline, 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02055079, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2018; AzTrials last refreshed its copy on 8 Nov 2026.