Does the ALDOsterone:RENin ratio predict the efficacy of spironolactone over bendroflumethiazide in hypertension?

ISRCTN	ISRCTN93126600
DOI	https://doi.org/10.1186/ISRCTN93126600
Secondary identifying numbers	N/A

Submission date: 21/03/2007
Registration date: 13/04/2007
Last edited: 28/09/2018

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Thomas MacDonald
Scientific

Level 7
Hypertension Research Centre
Ninewells Hospital and Medical School
Dundee
DD1 9SY
United Kingdom

Phone	+44 (0)1382 632852
Email	t.m.macdonald@dundee.ac.uk

Study information

Study design	A double-blind, randomised, crossover, controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
Study type	Treatment
Scientific title	Does the ALDOsterone:RENin ratio predict the efficacy of spironolactone over bendroflumethiazide in hypertension?
Study acronym	RENALDO
Study objectives	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(s)	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).
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Spironolactone, bendroflumethiazide
Primary outcome measure	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 study start date	01/08/2002
Completion date	01/02/2006

Eligibility

Participant type(s)	Patient
Age group	Not Specified
Sex	Not Specified
Target number of participants	120
Key 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
Key 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
Date of first enrolment	01/08/2002
Date of final enrolment	01/02/2006

Locations

Countries of recruitment

Scotland
United Kingdom

Study participating centre

Level 7

Dundee
DD1 9SY
United Kingdom

Sponsor information

Ninewells Hospital & Medical School (UK)
Hospital/treatment centre

c/o Dr Harikrishnan Parthasarathy, Specialist Registrar
Dundee
DD1 9SY
Scotland
United Kingdom

Email	krishnankala@hotmail.com
"ROR"	https://ror.org/039c6rk82

Funders

Funder type

Government

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

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol article	protocol	09/05/2007		Yes	No
Results article	results	01/01/2010		Yes	No

Editorial Notes

28/09/2018: Publication reference added.