RAS Quantification in Patients With Aliskiren or Candesartan (RASQAL)
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.
|Hypertension Chronic Kidney Disease Proteinuria||Other: RAS blockade discontinuation Drug: Aliskiren Drug: Candesartan||Phase 4|
|Study Design:||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)|
- Mass spectrometry RAS peptide quantification [ Time Frame: 2 months ]Quantitative RAS peptide changes determined by mass spectrometry after a 2-month treatment with aliskiren or candesartan
- Blood pressure [ Time Frame: 2 months ]Blood pressure reduction, determined by ambulatory blood pressure measurements at study start and end
- Proteinuria [ Time Frame: 2 months ]Proteinuria reduction, measured by urinary albumin/creatinine ratio at study start and end
|Study Start Date:||December 2012|
|Study Completion Date:||February 2016|
|Primary Completion Date:||February 2016 (Final data collection date for primary outcome measure)|
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 regimenDrug: 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 regimenDrug: Candesartan
Other Name: Atacand
Please refer to this study by its ClinicalTrials.gov identifier: NCT01827202
|Medical University of Vienna, Department of Internal Medicine III, Division of Nephrology and Dialysis|
|Vienna, Austria, 1090|
|Principal Investigator:||Marcus D Saemann, MD||Medical University of Vienna|