RAS Quantification in Patients With Aliskiren or Candesartan

NCT ID: NCT01827202

Last Updated: 2016-03-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2016-02-29

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.

Conditions

Hypertension; Chronic Kidney Disease; Proteinuria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SCREENING
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

RAS blockade discontinuation

Intervention Type: OTHER

In the initial two weeks of the study, all RAS blockade will be eliminated from the subjects' antihypertensive regimen

Aliskiren

Intervention Type: DRUG

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.

Group Type: ACTIVE_COMPARATOR

RAS blockade discontinuation

Intervention Type: OTHER

In the initial two weeks of the study, all RAS blockade will be eliminated from the subjects' antihypertensive regimen

Candesartan

Intervention Type: DRUG

Interventions

RAS blockade discontinuation

In the initial two weeks of the study, all RAS blockade will be eliminated from the subjects' antihypertensive regimen

Intervention Type: OTHER

Aliskiren

Intervention Type: DRUG

Candesartan

Intervention Type: DRUG

Other Intervention Names

Rasilez; Atacand

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Marcus Saemann

Assoc. Prof. Priv.-Doz. Dr.med.univ.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marcus D Saemann, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna

Locations

Medical University of Vienna, Department of Internal Medicine III, Division of Nephrology and Dialysis

Vienna, Vienna, Austria

Countries

Austria

Other Identifiers

EK-Nr. 011/2012

Identifier Type: -

Identifier Source: org_study_id