The Efficacy of Spironolactone in Patients With Resistant Hypertension

December 3, 2010 updated by: Sheffield Teaching Hospitals NHS Foundation Trust

A Randomised, Placebo Controlled Trial of the Efficacy of the Addition of Spironolactone to Modern Antihypertensive Treatment Regimens in Patients With Resistant Hypertension

To determine the efficacy of the addition of spironolactone to modern blood pressure lowering treatment regimens in patients with resistant hypertension (whose blood pressure is uncontrolled despite three blood pressure lowering drugs)

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Objective: To assess the antihypertensive efficacy of adding spironolactone to the antihypertensive treatment of patients with resistant hypertension.

Background and Rationale: The proportion of hypertensive patients meeting the definition of resistant hypertension is growing rapidly as doctors use more combination antihypertensive treatments in order to reach lower target blood pressures. Spironolactone is often used in specialist clinics for patients with resistant hypertension although it is currently only licensed in the UK for use in hypertension complicated by primary hyperaldosteronism. Uncontrolled studies suggest that spironolactone is a very effective antihypertensive in the modern management of resistant hypertension but we could find no randomised trials in this setting. In the Sheffield Hypertension Clinic spironolactone is currently used as one of the drugs of choice in patients with resistant hypertension, particularly in women and is anecdotally often very effective.

Study methods. The study will be a double- blind randomised placebo controlled trial with a parallel group design assessing the addition of 25mg spironolactone to existing antihypertensive treatment, titrated to 50mg if necessary in 40 patients with resistant hypertension (20 patients per group) over a period of 6 weeks. Resistant hypertension will be defined as: blood pressures not adequately controlled (systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) >85 mmHg in clinic and on ambulatory blood pressure monitoring) despite treatment with the maximum tolerated dose of three antihypertensive agents. All patients' current antihypertensive treatment will include a thiazide diuretic and at least one of a beta-blocker, angiotensin converting enzyme inhibitor or angiotensin II receptor antagonist. The primary endpoint will be the difference between the spironolactone and placebo groups in change in daytime average systolic blood pressure on 24-hour ambulatory blood pressure monitoring from day 0 to day 42.

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • South Yorkshire
      • Sheffield, South Yorkshire, United Kingdom, S10 2JF
        • Clinical Research Facility, Royal Hallamshire Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Aged over 18 years
  • Hypertension (essential or secondary) managed in Sheffield Hypertension Clinic or general practice or both.
  • Blood pressures not adequately controlled (systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) >85 mmHg in clinic and on ambulatory blood pressure monitoring) despite treatment with the maximum tolerated dose of three antihypertensive agents.
  • Additional antihypertensive treatment deemed appropriate by the patients' doctor.
  • Patients' current antihypertensive treatment includes a thiazide diuretic and at least one of a beta-blocker, angiotensin converting enzyme inhibitor or angiotensin II receptor antagonist.

Exclusion Criteria:

  • Definite indication or contraindication for spironolactone
  • Known Conn's syndrome (definite indication for spironolactone)
  • Heart failure NYHA class III or IV (definite indication for spironolactone)
  • Known hepatic failure or significant cirrhosis
  • Known pregnancy or women planning pregnancy
  • Women of child bearing potential not using adequate contraceptive methods
  • Serum creatinine > 221µmol/l
  • Serum Potassium > 5.0mmol/l
  • Clinic blood pressure or daytime ambulatory blood pressure >240/120

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
The primary endpoint will be the difference between the spironolactone and placebo groups in change in daytime average systolic blood pressure on ABPM from day 0 to day 42

Secondary Outcome Measures

Outcome Measure
Difference between the spironolactone and placebo groups in change in daytime average diastolic blood pressure on ABPM from day 0 to day 42
Difference between the spironolactone and placebo groups in change in systolic and diastolic clinic blood pressure (mean of 2nd and 3rd readings) from day 0 to day 42
Difference between the spironolactone and placebo groups in change in serum creatinine from day 0 to day 42
Difference between the spironolactone and placebo groups in change in serum potassium from day 0 to day 42
Difference between the spironolactone and placebo groups in change in body weight from day 0 to day 42

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sheffield Teaching Hospitals NHS Foundation Trust

Collaborators

University of Sheffield

Investigators

  • Principal Investigator: Peter R Jackson, MB ChB, PhD, University of Sheffield

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2007

Study Completion (Actual)

December 1, 2008

Study Registration Dates

First Submitted

February 1, 2007

First Submitted That Met QC Criteria

February 1, 2007

First Posted (Estimate)

February 2, 2007

Study Record Updates

Last Update Posted (Estimate)

December 6, 2010

Last Update Submitted That Met QC Criteria

December 3, 2010

Last Verified

February 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STH14399

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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