Optimalization of Nephroprotection Using Agents Inhibiting Renin-Angiotensin-Aldosterone System - Full Text View

Sponsored by:	Medical University of Gdansk
Information provided by:	Medical University of Gdansk
ClinicalTrials.gov Identifier:	NCT00528385

Purpose

The main purpose of the study is find whether the addition of aldosterone antagonist, spironolactone to dual renin-angiotensin-aldosterone system blockade involving angiotensin converting enzyme inhibitor and AT-1 angiotensin II receptor blocker leads to the reduction of proteinuria, main prognostic marker of chronic kidney disease progression.

Condition	Intervention
Chronic Kidney Disease Proteinuria	Drug: Spironolactone (Spironol) 25 mg

Drug Information available for: Telmisartan Spironolactone Aldosterone Cilazapril

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Crossover Assignment, Safety/Efficacy Study
Official Title:	Influence of Adding Aldosterone Receptor Blocker to Dual Renin-Angiotensin-Aldosterone System Blockade on Proteinuria

Further study details as provided by Medical University of Gdansk:

Primary Outcome Measures:

Investigate the antiproteinuric effect of adding aldosterone antagonist, spironolactone to the combination therapy with angiotensin converting enzyme inhibitor and AT-1 receptor blocker in maximal recommended doses.

Secondary Outcome Measures:

Investigate the effect of the study intervention on urine excretion of N-acetyl-β-D-glucosaminidase, alfa1-microglobulin and amino-terminal propeptide of type III procollagen.

Study Start Date:

March 2005

Intervention Details:

In the 8-weeks run-in period ACEI, cilazapril (5 mg), telmisartan (80 mg) and hydrochlorotiazyd (12.5 mg) were administered to achieve the target blood pressure below 130/80 mmHg. Next, they were randomly assigned to add (or not) 25 mg of spironolactone in two active treatment periods lasting 8 weeks each.

Detailed Description:

The renin-angiotensin-aldosterone system (RAAS) plays an important role in the progression of chronic kidney diseases (CKD), and inhibition of the RAAS with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB) may retard CKD progression. Dual pharmacological blockade of the RAAS with ACEI and ARB is recommended as a standard renoprotective management at least in patients with nondiabetic proteinuric CKD. However, neither ACEI nor ARB, even in high doses or in concomitant usage, abrogate the progression of CKD completely. Innovative approaches are needed to keep patients with CKD off dialysis. Additional blockade of the aldosterone pathway may prove to be such beneficial therapeutic concept.Aldosterone, a final effector of RAAS plays a significant role in the pathogenesis of CKD independently of angiotensin II through direct cellular action. This includes promoting an inflammatory response, endothelial dysfunction, and fibrosis by increasing plasminogen activator inhibitor (PAI-1) and transforming growth factor beta-1 (TGF-beta-1) expression and stimulation reactive oxygen species.A number of observations suggest nongenomic vasoconstrictor action of aldosterone leading to raise arterial and glomerular capillary pressure.Given these facts additional administration of aldosterone antagonist to combination treatment with ACEI and ARB, so called triple RAAS blockade may provide additional renal protection. To shed more light on this issue, we performed a randomised open controlled study to evaluate the influence of triple RAAS therapy on surrogate markers of kidney injury, i.e. proteinuria, markers of tubular involvement and kidney fibrosis.

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

chronic kidney disease
stable proteinuria above 300 mg/24 hours (no variations above 25% in the last 6 months)
normal or slightly impaired stable renal function defined as serum creatinine level below 1.7 mg/dl (eGFR > 45 ml/min)

Exclusion Criteria:

nephrotic syndrome
steroids or other immunosuppressive treatment minimum during six months before the study
diabetes mellitus
potassium serum level > 5.1 mEq/L
albumin serum level < 2.0mg/dL
creatinine serum level >2 mg/dl
current diagnosis of heart failure New York Heart Association (NYHA) Class II-IV
clinically significant valvular heart disease or second or third degree heart block without a pacemaker
history of hypertensive encephalopathy, cerebrovascular accident or transient ischemic cerebral attack
history of myocardial infarction, unstable angina pectoris, coronary bypass surgery, or any percutaneous coronary intervention
history of malignancy including leukemia and lymphoma (but not basal cell skin carcinoma) within the past five years
pregnant or nursing women
any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs.
history of alcohol abuse
NSAID abuse (more than 2 doses per week)
known or suspected contraindications to the study medications, including history of allergy to ACE inhibitors, AT-1 receptor blockers and aldosterone antagonists

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00528385

Sponsors and Collaborators

Medical University of Gdansk

Investigators

Principal Investigator:

Boleslaw Rutkowski, MD, PhD

Department of Nephrology Transplantology and Internal Medicine. Medical University of Gdansk.

More Information

Study ID Numbers:	ST-4/RAAS/02
Study First Received:	September 11, 2007
Last Updated:	September 11, 2007
ClinicalTrials.gov Identifier:	NCT00528385
Health Authority:	Poland: Ministry of Health

Keywords provided by Medical University of Gdansk:

Proteinuria
Renin-Angiotensin-Aldosterone System
Aldosterone Antagonists

Study placed in the following topic categories:

Signs and Symptoms
Renal Insufficiency
Proteinuria
Urologic Diseases
Urination Disorders
Renal Insufficiency, Chronic

Kidney Failure, Chronic
Telmisartan
Kidney Diseases
Cilazapril
Spironolactone
Kidney Failure

Additional relevant MeSH terms:

Urological Manifestations
Aldosterone Antagonists
Natriuretic Agents
Therapeutic Uses
Hormone Antagonists

Physiological Effects of Drugs
Diuretics
Hormones, Hormone Substitutes, and Hormone Antagonists
Cardiovascular Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009