HypertensionPhase 4RASQALNCT01827202
RAS Quantification in Patients With Aliskiren or Candesartan
A Phase 4 study testing RAS blockade discontinuation, Aliskiren and Candesartan in people with Hypertension and Chronic Kidney Disease, run by Medical University of Vienna at 1 site in Austria.
Trial summary
Forced blockade of the renin-angiotensin-system (RAS) by using direct renin inhibition (DRI) has long been propagated to effectuate beneficial outcomes. However, recent large clinical trials have outlined harmful effects for DRI in combination with other forms of RAS blockade. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Hypertension, Chronic Kidney Disease, Proteinuria
- What is being tested?
- RAS blockade discontinuation, Aliskiren and Candesartan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteAustria
- Study dates
- Dec 2012to Feb 2016
- Phase
- Phase 4
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Chronic kidney disease stages III-IV (defined by modification of diet in renal disease (MDRD) formula)
- Urinary albumin to creatinine ratio (UACR) >300mg/g, UACR >200mg/g if already receiving RAS blockade
- Arterial hypertension
Who cannot join
- Age <18 years
- Diabetes mellitus type 2 (defined by WHO criteria)
- Chronic kidney disease stage V (end-stage renal disease)
- UACR >3500mg/g
- Severe hypertension (systolic blood pressure >180mmHg)
- Pregnancy
Trial locations and contacts
1 site in 1 country.
Austria1 site
Medical University of Vienna, Department of Internal Medicine III, Division of Nephrology and Dialysis
Vienna, State of Vienna, 1090
About this study
Official title: Renin-Angiotensin-System Quantification in Patients Treated With Aliskiren or Candesartan (RASQAL)
Forced blockade of the renin-angiotensin-system (RAS) by using direct renin inhibition (DRI) has long been propagated to effectuate beneficial outcomes. However, recent large clinical trials have outlined harmful effects for DRI in combination with other forms of RAS blockade. To date, information regarding DRI as RAS-blocking monotherapy is very limited. Furthermore, it remains to be elucidated how DRI and angiotensin receptor blockers affect the so-called 'classical' and 'alternative' RAS molecularly. As components of the 'alternative' RAS (e.g. Ang 1-7) have moved into research focus, it would be of importance to determine angiotensin regulation with medical RAS blockade.
In this prospective, single-center randomized trial over 10 weeks, 24 patients with chronic kidney disease (CKD) stage III-IV (eGFR 15-59 ml/min) will be randomized to take either aliskiren (up to 300 mg per day) or candesartan (up to 16 mg per day) after a two week run-in phase where all RAS-blockers are eliminated. The investigators will then employ a novel mass spectrometry-based quantification method (after run-in and 10 weeks) to capture the concentrations of ten different angiotensin peptides (including angiotensin I and II, angiotensin 1-7 and angiotensin 1-5).
Read more
The investigators hypothesize that significant differences exist between angiotensin levels in CKD patients with DRI compared to angiotensin receptor blockers. Specifically, the investigators expect to determine the regulation of the alternative RAS represented by angiotensin 1-7 with proximal versus distal blockade of the system.
Our data might contribute to a more profound understanding of results from registries and clinical trials beyond the clinical effects of RAS blockade. Further, the study's results might help to individualize and optimize RAS-blocking therapy strategies in CKD patients.
- Conditions
- Hypertension, Chronic Kidney Disease, Proteinuria
- Being tested
- RAS blockade discontinuation, Aliskiren, Candesartan
- Keywords
- renin-angiotensin-system, RAS blockade
- Medical subject headings
- Hypertension, Renal Insufficiency, Chronic, Proteinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RAS blockade discontinuationOther
In the initial two weeks of the study, all RAS blockade will be eliminated from the subjects' antihypertensive regimen
AliskirenDrug
Also called Rasilez
CandesartanDrug
Also called Atacand
| Study group | Role | What they receive |
|---|---|---|
| Aliskiren | Active comparator | After a two-week phase where all RAS blockade is eliminated, patients in this arm will commence taking aliskiren 150 mg once daily for 4 weeks. Thereafter, the dose will be increased to 300 mg once daily for another 4 weeks. Receives: Other: RAS blockade discontinuation; Drug: Aliskiren |
| Candesartan | Active comparator | After a two-week phase where all RAS blockade is eliminated, patients in this arm will commence taking candesartan 8 mg once daily for 4 weeks. Thereafter, the dose will be increased to 16 mg once daily for another 4 weeks. Receives: Other: RAS blockade discontinuation; Drug: Candesartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mass spectrometry RAS peptide quantification
Quantitative RAS peptide changes determined by mass spectrometry after a 2-month treatment with aliskiren or candesartan
Measured: 2 months
Secondary outcomes (2)
Blood pressure
Blood pressure reduction, determined by ambulatory blood pressure measurements at study start and end
Measured: 2 months
Proteinuria
Proteinuria reduction, measured by urinary albumin/creatinine ratio at study start and end
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2013 (estimated)
- Study startDec 2012
- Primary completionFeb 2016
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypertensionStudies 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 4
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marcus Saemann, Medical University of Vienna
- Investigators
- Marcus D Saemann, MD, Principal investigator, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01827202
- Sponsor's protocol ID
- EK-Nr. 011/2012
- Acronym
- RASQAL
- Status last verified
- Mar 2016
- First submitted
- 4 Apr 2013
- Last updated
- 16 Mar 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Renin-Angiotensin-System Quantification in Patients Treated With Aliskiren or Candesartan (RASQAL)
- ClinicalTrials.gov ID
- NCT01827202
- Acronym / sponsor ID
- RASQAL / EK-Nr. 011/2012
- Conditions
- Hypertension, Chronic Kidney Disease, Proteinuria
- Keywords
- renin-angiotensin-system, RAS blockade
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- Dec 2012
- Primary completion
- Feb 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 9 Apr 2013 (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.
Forced blockade of the renin-angiotensin-system (RAS) by using direct renin inhibition (DRI) has long been propagated to effectuate beneficial outcomes. However, recent large clinical trials have outlined harmful effects for DRI in combination with other forms of RAS blockade. To date, information regarding DRI as RAS-blocking monotherapy is very limited. Furthermore, it remains to be elucidated how DRI and angiotensin receptor blockers affect the so-called 'classical' and 'alternative' RAS molecularly. As components of the 'alternative' RAS (e.g. Ang 1-7) have moved into research focus, it would be of importance to determine angiotensin regulation with medical RAS blockade.
In this prospective, single-center randomized trial over 10 weeks, 24 patients with chronic kidney disease (CKD) stage III-IV (eGFR 15-59 ml/min) will be randomized to take either aliskiren (up to 300 mg per day) or candesartan (up to 16 mg per day) after a two week run-in phase where all RAS-blockers are eliminated. The investigators will then employ a novel mass spectrometry-based quantification method (after run-in and 10 weeks) to capture the concentrations of ten different angiotensin peptides (including angiotensin I and II, angiotensin 1-7 and angiotensin 1-5).
The investigators hypothesize that significant differences exist between angiotensin levels in CKD patients with DRI compared to angiotensin receptor blockers. Specifically, the investigators expect to determine the regulation of the alternative RAS represented by angiotensin 1-7 with proximal versus distal blockade of the system.
Our data might contribute to a more profound understanding of results from registries and clinical trials beyond the clinical effects of RAS blockade. Further, the study's results might help to individualize and optimize RAS-blocking therapy strategies in CKD patients.
Study design
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aliskiren | Active comparator | Other: RAS blockade discontinuation, Drug: AliskirenAfter a two-week phase where all RAS blockade is eliminated, patients in this arm will commence taking aliskiren 150 mg once daily for 4 weeks. Thereafter, the dose will be increased to 300 mg once daily for another 4 weeks. |
| Candesartan | Active comparator | Other: RAS blockade discontinuation, Drug: CandesartanAfter a two-week phase where all RAS blockade is eliminated, patients in this arm will commence taking candesartan 8 mg once daily for 4 weeks. Thereafter, the dose will be increased to 16 mg once daily for another 4 weeks. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Chronic kidney disease stages III-IV (defined by modification of diet in renal disease (MDRD) formula)
- Urinary albumin to creatinine ratio (UACR) >300mg/g, UACR >200mg/g if already receiving RAS blockade
- Arterial hypertension
Key exclusion criteria (6 listed)
- Age <18 years
- Diabetes mellitus type 2 (defined by WHO criteria)
- Chronic kidney disease stage V (end-stage renal disease)
- UACR >3500mg/g
- Severe hypertension (systolic blood pressure >180mmHg)
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 |
|---|---|---|
| RAS blockade discontinuationIn the initial two weeks of the study, all RAS blockade will be eliminated from the subjects' antihypertensive regimen | Other | Aliskiren, Candesartan |
| AliskirenAlso: Rasilez | Drug | Aliskiren |
| CandesartanAlso: Atacand | Drug | Candesartan |
Primary outcome
Mass spectrometry RAS peptide quantification
Time frame: 2 months
Quantitative RAS peptide changes determined by mass spectrometry after a 2-month treatment with aliskiren or candesartan
2 secondary outcomes
Blood pressure
Time frame: 2 months
Proteinuria
Time frame: 2 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2016.
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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.
Marcus D Saemann, 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 4 study testing RAS blockade discontinuation, Aliskiren and Candesartan in people with Hypertension and Chronic Kidney 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 3 inclusion and 6 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: finished, as of the sponsor's last update on 16 Mar 2016. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mass spectrometry RAS peptide quantification (time frame: 2 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Mar 2016.