RAS Quantification in Patients With Aliskiren or Candesartan (RASQAL)

Medical University of Vienna

Status and phase: Completed; Phase 4

Conditions: Chronic Kidney Disease; Hypertension; Proteinuria

Treatments: Drug: Candesartan; Other: RAS blockade discontinuation; Drug: Aliskiren

Study type: Interventional

Funder types: Other

Identifiers

NCT01827202

EK-Nr. 011/2012

Details and patient eligibility

About

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.

Enrollment: 24 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No 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

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

Trial design

Primary purpose: Screening

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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24 participants in 2 patient groups

Aliskiren

Active Comparator group

Description:

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.

Treatment:

Drug: Aliskiren

Other: RAS blockade discontinuation

Candesartan

Active Comparator group

Description:

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.

Treatment:

Other: RAS blockade discontinuation

Drug: Candesartan