Condition category
Circulatory System
Date applied
21/03/2007
Date assigned
13/04/2007
Last edited
08/08/2011
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Thomas MacDonald

ORCID ID

Contact details

Level 7
Hypertension Research Centre
Ninewells Hospital and Medical School
Dundee
DD1 9SY
United Kingdom
+44 (0)1382 632852
t.m.macdonald@dundee.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Acronym

RENALDO

Study hypothesis

Primary objective:
To test the hypothesis that the aldosterone:renin ratio predicts the antihypertensive response to spironolactone, specifically that the effect of spironolactone 50 mg is greater than that of bendroflumethiazide 2.5 mg in hypertensive subjects with high aldosterone:renin ratios.

Secondary objectives: to determine whether -
1. Bendroflumethiazide induces adverse metabolic abnormalities, especially in subjects with high aldosterone:renin ratios
2. Baseline renin measurement predicts the antihypertensive response to spironolactone and/or bendroflumethiazide

Ethics approval

The main study and sub-studies have ethical approval from Tayside Committee on Medical Research Ethics and West Ethics Committee on the 20th June 2002 (ref: 2006/01).

Study design

A double-blind, randomised, crossover, controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

Hypertension/cardiovascular diseases

Intervention

120 hypertensive subjects are randomised to 12 weeks treatment with spironolactone 50 mg once daily and 12 weeks treatment with bendroflumethiazide 2.5 mg once daily. The two treatment periods are separated by a two-week washout period.

Investigators and subjects do not know the order of the treatment periods, which is according to a computer generated randomisation list. Randomisation is stratified by aldosterone:renin ratio to include equal numbers of subjects with high and low aldosterone:renin ratios. This is necessary as in an unselected population, only 15% of subjects will have an aldosterone:renin ratio greater than 750.

Intervention type

Drug

Phase

Not Specified

Drug names

Spironolactone, bendroflumethiazide

Primary outcome measures

The primary endpoint is the difference in mean 24-hour blood ambulatory pressure recorded at the end of each 12-week treatment period.

Secondary outcome measures

Secondary endpoints include the differences between the following measurements taken at the end of each 12-week treatment period:
1. Mean daytime ambulatory blood pressure
2. Mean night time ambulatory blood pressure
3. Mean clinic blood pressure defined as mean of mean clinic BPs on both penultimate and final days of treatment periods
4. Clinical biochemistry measurements of plasma potassium (K+), magnesium (Mg2+), creatinine, triglycerides, cholesterol and High Density Lipoprotein (HDL) cholesterol

Overall trial start date

01/08/2002

Overall trial end date

01/02/2006

Reason abandoned

Eligibility

Participant inclusion criteria

1. Mild-to-moderate hypertension with daytime mean Ambulatory Blood Pressure Monitoring (ABPM) systolic Blood Pressure (BP) greater than 140 mmHg
2. Either untreated or on stable treatment for at least two weeks
3. Either:
a. aldosterone:renin ratio greater than 750 and plasma aldosterone greater than 250 pmol/l, or
b. aldosterone:renin ratio less than 300 and plasma renin activity less than 10 ng/ml/h
4. No clinically significant abnormalities on screening laboratory results
5. Written informed consent

Participant type

Patient

Age group

Not Specified

Gender

Not Specified

Target number of participants

120

Participant exclusion criteria

1. Females of child-bearing potential not using reliable contraception
2. Subjects on more than four classes of anti-hypertensive drugs at screening
3. Secondary hypertension other than hyperaldosteronism
4. Addison’s disease
5. Severe or malignant hypertension
6. Subjects who take and are unable to discontinue taking a thiazide diuretic or potassium sparing diuretic
7. Serum potassium less than 3.3 or greater than 5 mmol/l two weeks after discontinuing diuretics
8. Serum creatinine greater than 160 μmol/l
9. Subjects intolerant of spironolactone or thiazide diuretics
10. Subjects who have taken spironolactone or potassium canrenoate in the previous three months
11. Previous Myocardial Infarction (MI) or Cardiovascular Accident (CVA)
12. Chronic Heart Failure (CHF)
13. Any condition that would:
a. interfere with the ability to provide informed consent
b. place at increased risk
c. confound interpretation of results

Recruitment start date

01/08/2002

Recruitment end date

01/02/2006

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Level 7
Dundee
DD1 9SY
United Kingdom

Sponsor information

Organisation

Ninewells Hospital & Medical School (UK)

Sponsor details

c/o Dr Harikrishnan Parthasarathy
Specialist Registrar
Dundee
DD1 9SY
United Kingdom
krishnankala@hotmail.com

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

Chief Scientist Office, Scottish Executive Health Department (UK) (ref: BA-01-25)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Study protocol: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17490489

Publication citations

  1. Study protocol

    Parthasarathy HK, Alhashmi K, McMahon AD, Struthers AD, Connell JM, McInnes GT, Ford I, MacDonald TM, Does the aldosterone:renin ratio predict the efficacy of spironolactone over bendroflumethiazide in hypertension? A clinical trial protocol for RENALDO (RENin-ALDOsterone) study., BMC Cardiovasc Disord, 2007, 7, 14, doi: 10.1186/1471-2261-7-14.

Additional files

Editorial Notes