RAS Quantification in Patients With Aliskiren or Candesartan

Hypertension Clinical Trial

— RASQAL  

Official title:

Renin-Angiotensin-System Quantification in Patients Treated With Aliskiren or Candesartan (RASQAL)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01827202
• Other study ID #: EK-Nr. 011/2012
• Status: Completed
• Phase: Phase 4
• First received: April 4, 2013
• Last updated: March 14, 2016
• Start date: December 2012
• Est. completion date: February 2016

Study information

• Verified date: March 2016
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Austrian Medicines and Medical Devices Agency
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 99 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Screening

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Hypertension
• Kidney Diseases
• Proteinuria
• Renal Insufficiency, Chronic

Intervention

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

• Candesartan

Locations

Country	Name	City	State
Austria	Medical University of Vienna, Department of Internal Medicine III, Division of Nephrology and Dialysis	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mass spectrometry RAS peptide quantification	Quantitative RAS peptide changes determined by mass spectrometry after a 2-month treatment with aliskiren or candesartan	2 months	No
Secondary	Blood pressure	Blood pressure reduction, determined by ambulatory blood pressure measurements at study start and end	2 months	No
Secondary	Proteinuria	Proteinuria reduction, measured by urinary albumin/creatinine ratio at study start and end	2 months	No