RASQAL: RAS Quantification in Patients With Aliskiren or Candesartan

Sponsor

Medical University of Vienna (Other)

Overall Status

Completed

CT.gov ID

NCT01827202

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

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

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Screening

Official Title:

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

Study Start Date :

Dec 1, 2012

Actual Primary Completion Date :

Feb 1, 2016

Actual Study Completion Date :

Feb 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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 Names: Atacand

Arm

Intervention/Treatment

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 Names:

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 Names:

Atacand

Outcome Measures

Primary Outcome Measures

Mass spectrometry RAS peptide quantification [2 months]
Quantitative RAS peptide changes determined by mass spectrometry after a 2-month treatment with aliskiren or candesartan

Secondary Outcome Measures

Blood pressure [2 months]
Blood pressure reduction, determined by ambulatory blood pressure measurements at study start and end
Proteinuria [2 months]
Proteinuria reduction, measured by urinary albumin/creatinine ratio at study start and end

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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