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. Addisons 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
-
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.