Hypertension and Striatin Gene Structure Related to Aldo Phenotype
Phase: PHASE4
Conditions: Hypertension, Genetics Hypertension
Sponsor: Brigham and Women's Hospital

 
PROTOCOL 
 
Official title:  
MR Antagonist – Eplerenone vs Amolidipine and STRIATIN 
 
Document number:  
NCT03683069 
 
Date:   
 
 
12/14/2024  
 

Flow Chart – Study Design (FIG 1) 
 
Subjects in the RPDR cohort were recruited to the study using Patient Gateway to 
specifically invite their participation. After documenting that the subject had the correct 
striatin genotype, current antihypertensive medications were discontinued. To assess the 
salt sensitivity of their blood pressure (SSBP) six - seven days of a restricted salt diet 
(Visit 1) was provided with blood pressure (BP) measured seated, daily in the morning 
at home and in the office at the end of the diet study. Then, the diet was changed to a 
liberal salt intake (Visit 2), and the BP studies were repeated. At the conclusion of the 
SSBP study, the subjects were randomized to the eplerenone or amlodipine arms and 
resumed a normal diet. After 3 weeks of the normal salt diet, the diet was changed to a 
liberal salt intake. Subjects continued to measure home BPs and returned to the clinic on 
the 7th day to have office BPs measured (Visit 3). If the last two home BPs were < 140/90 
mmHg, goal BP was achieved, and the subjects were maintained on the present dose. If 
goal BPs were not achieved, then the doses were increased. The whole process is 
repeated for a second month (Visit 4); if goal BP is not achieved, a third dose increase is 
instituted, and the process is repeated for a third month (Visit 5). A 24-hour ambulatory 
BP was obtained at the time of randomization and at Visit 5 on all subjects when they 
were on a liberal salt diet.                                                                                                                          
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
FIG 1. 
Visit 1
Visit 2
Visit 4
Visit 5
Washout anti-
hypertensives
Weeks
-4
Dose titration if BP > 140/90 mmHg
Liberal Na+ Diet (1-14 days)
Restricted Na+ Diet (6-10 days)
24-hour BP monitoring
-2
-1
0
4
8
12
E P L E R E N O N E
A M L O D I P I N E
Visit 3
Visit 4
Visit 5
Visit 3
Study drug 
randomization

Participant Flow – Consort Diagram (FIG 2) 
 
There were 2786 individuals invited to participate in the study, of which 400 met the 
screening and genotype criteria. Of these, 67 were randomized to a treatment arm. Two 
subjects dropped out before receiving any medications. Thus, of the 65 enrolled, 33 were 
in the eplerenone limb and 32 in the amlodipine limb. All but one completed the entire 
study after randomization.  
 
 
 
 
 
FIG 2. 
Assessed for genotype eligibility: 400
Qualified for study and agreed to enroll: 80
Excluded following first screen: 280
• 256 did not have correct genotype
• 23 had correct genotype but
• 8 voluntarily withdrew participation
• 11 lost to follow-up
• 4 excluded for newly-identified 
health conditions
• 1 had inconclusive genotyping results but 
withdrew participation
Excluded before randomization: 13
• 7 discontinued by study staff
• 2 elevated BP during washout 
phase
• 5 did not meet 140/90 mmHg BP 
threshold after liberal salt diet
• 6 voluntarily withdrew participation
Assessed for eligibility at second in-person screen: 120
Excluded following second screen: 40
• 27 did not meet eligibility criteria
• 6 voluntarily withdrew participation
• 7 lost to follow-up
Completed final study visit: 32
Completed final study visit: 33
Excluded after randomization: 2 
• 1 discontinued by study staff 
due to non-compliance
• 1 voluntarily withdrew 
participation
Did not proceed to genotyping step: 2386
Either did not meet eligibility criteria, 
voluntarily withdrew participation, or lost to 
follow-up
Filled out pre-screening questionnaire: 2786
Randomized to amlodipine and began study drug: 32
Randomized to eplerenone and began study drug: 35