Clinical trial NCT01827202: RAS Quantification in Patients With Aliskiren or Candesartan
Official title: Renin-Angiotensin-System Quantification in Patients Treated With Aliskiren or Candesartan (RASQAL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension
Chronic Kidney Disease
Proteinuria
Keywords: renin-angiotensin-system
RAS blockade
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2013-04-09
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief 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.


Eligibility 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

Primary outcomes:
measure: Mass spectrometry RAS peptide quantification
timeFrame: 2 months
Secondary outcomes:
measure: Blood pressure
timeFrame: 2 months
measure: Proteinuria
timeFrame: 2 months
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna, Department of Internal Medicine III, Division of Nephrology and Dialysis
Study officials:
affiliation: Medical University of Vienna
name: Marcus D Saemann, MD
role: PRINCIPAL_INVESTIGATOR
References: