Comparing the Effects of Spironolactone With Chlortalidone on LV Mass in Patients With CKD

Summary

In stage 3 chronic kidney disease (CKD) the risk of death due to cardiovascular causes is high and greatly exceeds the risk of progression to end stage renal failure. This high cardiovascular risk is predominantly due to sudden cardiac death and heart failure, manifestations of left ventricular hypertrophy and fibrosis. Aldosterone appears to play an important role in the causation of this myocardial disease both by direct inflammatory and fibrotic myocardial effects and via increased arterial stiffness due to hypertrophy, inflammation, and fibrosis within the media of large arteries. Levels of aldosterone are high in CKD despite sodium overload and treatment with angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) drugs due to the twin phenomena of aldosterone escape and breakthrough. In a previous British Heart Foundation funded study, Birmingham investigators showed that the addition of the mineralocorticoid receptor blocker (MRB) spironolactone to background therapy with ACE inhibitors or ARBs caused reductions in the prognostically important parameters of arterial stiffness and LV mass. Because spironolactone therapy was also associated with significant falls in arterial pressure it remains possible that these effects were mediated simply by blood pressure reduction. In this multi-centre, randomised controlled study, the effects of treatment with spironolactone on LV mass and arterial stiffness in patients with stage 3 CKD on established ACE or ARB therapy will be compared to those of chlortalidone, a control anti-hypertensive agent. Early stage chronic kidney disease is highly prevalent and new, cost effective treatment strategies are required to reduce cardiovascular risk. This study is designed to provide the rationale for a larger study of morbidity and mortality with MRB therapy in early stage CKD.

Conditions

• Renal Insufficiency, Chronic
• Cardio-Renal Syndrome

Interventions

DRUG

Spironolactone

25mg orally once a day for 40 weeks

DRUG

Chlortalidone

25mg orally once a day for 40 weeks

Sponsors & Collaborators

• Royal Free Hospital NHS Foundation Trust

  collaborator OTHER

• University of Edinburgh

  collaborator OTHER

• University of Cambridge

  collaborator OTHER

• University Hospital Birmingham

  lead OTHER

Principal Investigators

• Gemma Slinn · University of Birmingham

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-06-30

Primary Completion

2018-02-28

Completion

2018-05-31

Countries

• United Kingdom

Study Locations