RAS Quantification in Patients With Aliskiren or Candesartan
Information source: Medical University of Vienna
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hypertension; Chronic Kidney Disease; Proteinuria
Intervention: RAS blockade discontinuation (Other); Aliskiren (Drug); Candesartan (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Medical University of Vienna Official(s) and/or principal investigator(s): Marcus D Saemann, MD, Principal Investigator, Affiliation: Medical University of Vienna
Overall contact: Marlies Antlanger, MD, Phone: +4369917114489, Email: marlies.antlanger@meduniwien.ac.at
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. 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.
Clinical Details
Official title: Renin-Angiotensin-System Quantification in Patients Treated With Aliskiren or Candesartan (RASQAL)
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Screening
Primary outcome: Mass spectrometry RAS peptide quantification
Secondary outcome: Blood pressureProteinuria
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
Marlies Antlanger, MD, Phone: +4369917114489, Email: marlies.antlanger@meduniwien.ac.at
Medical University of Vienna, Department of Internal Medicine III, Division of Nephrology and Dialysis, Vienna 1090, Austria; Recruiting Marlies Antlanger, MD, Phone: +4369917114489, Email: marlies.antlanger@meduniwien.ac.at Marcus D Saemann, MD, Principal Investigator Marlies Antlanger, MD, Sub-Investigator Johannes J Kovarik, MD, PhD, Sub-Investigator
Additional Information
Starting date: December 2012
Last updated: April 8, 2013
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