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RAS Quantification in Patients With Aliskiren or Candesartan (RASQAL)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by Medical University of Vienna
Sponsor:
Information provided by (Responsible Party):
Marcus Saemann, Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT01827202
First received: April 4, 2013
Last updated: April 8, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Hypertension
Chronic Kidney Disease
Proteinuria
Other: RAS blockade discontinuation
Drug: Aliskiren
Drug: Candesartan
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Screening
Official Title: Renin-Angiotensin-System Quantification in Patients Treated With Aliskiren or Candesartan (RASQAL)

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • Mass spectrometry RAS peptide quantification [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    Quantitative RAS peptide changes determined by mass spectrometry after a 2-month treatment with aliskiren or candesartan


Secondary Outcome Measures:
  • Blood pressure [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    Blood pressure reduction, determined by ambulatory blood pressure measurements at study start and end

  • Proteinuria [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    Proteinuria reduction, measured by urinary albumin/creatinine ratio at study start and end


Estimated Enrollment: 24
Study Start Date: December 2012
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Aliskiren
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.
Other: RAS blockade discontinuation
In the initial two weeks of the study, all RAS blockade will be eliminated from the subjects' antihypertensive regimen
Drug: Aliskiren
Other Name: Rasilez
Active Comparator: Candesartan
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.
Other: RAS blockade discontinuation
In the initial two weeks of the study, all RAS blockade will be eliminated from the subjects' antihypertensive regimen
Drug: Candesartan
Other Name: Atacand

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01827202

Contacts
Contact: Marlies Antlanger, MD +4369917114489 marlies.antlanger@meduniwien.ac.at

Locations
Austria
Medical University of Vienna, Department of Internal Medicine III, Division of Nephrology and Dialysis Recruiting
Vienna, Austria, 1090
Contact: Marlies Antlanger, MD    +4369917114489    marlies.antlanger@meduniwien.ac.at   
Principal Investigator: Marcus D Saemann, MD         
Sub-Investigator: Marlies Antlanger, MD         
Sub-Investigator: Johannes J Kovarik, MD, PhD         
Sponsors and Collaborators
Medical University of Vienna
Investigators
Principal Investigator: Marcus D Saemann, MD Medical University of Vienna
  More Information

No publications provided

Responsible Party: Marcus Saemann, Assoc. Prof. Priv.-Doz. Dr.med.univ., Medical University of Vienna
ClinicalTrials.gov Identifier: NCT01827202     History of Changes
Other Study ID Numbers: EK-Nr. 011/2012
Study First Received: April 4, 2013
Last Updated: April 8, 2013
Health Authority: Austria: Austrian Medicines and Medical Devices Agency

Keywords provided by Medical University of Vienna:
renin-angiotensin-system
RAS blockade

Additional relevant MeSH terms:
Urination Disorders
Hypertension
Kidney Diseases
Proteinuria
Renal Insufficiency, Chronic
Cardiovascular Diseases
Renal Insufficiency
Signs and Symptoms
Urologic Diseases
Urological Manifestations
Vascular Diseases
Candesartan
Candesartan cilexetil
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Antihypertensive Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014