Trial Outcomes & Findings for Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis Trial (NCT NCT02169089)

NCT ID: NCT02169089

Last Updated: 2023-08-01

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 79 participants
• Primary outcome timeframe: 56 weeks
• Results posted on: 2023-08-01

Participant Flow

Participant milestones

Measure	Spironolactone Spironolactone Spironolactone: Patients will be given Spironolactone 12.5 mg on week 0 (visit 2). Patients will be escalated to 25 mg daily Spironolactone or maximal tolerated dose over a 4-week period. Patients will continue treatment for an additional 48 weeks.	Placebo Placebo Placebo: Placebo
Overall Study STARTED	37	42
Overall Study COMPLETED	26	25
Overall Study NOT COMPLETED	11	17

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis Trial

Baseline characteristics by cohort

Measure	Spironolactone n=37 Participants Spironolactone Spironolactone: Patients will be given Spironolactone 12.5 mg on week 0 (visit 2). Patients will be escalated to 25 mg daily Spironolactone or maximal tolerated dose over a 4-week period. Patients will continue treatment for an additional 48 weeks.	Placebo n=42 Participants Placebo Placebo: Placebo	Total n=79 Participants Total of all reporting groups
Age, Continuous	65.5 years STANDARD_DEVIATION 8.3 • n=5 Participants	63.2 years STANDARD_DEVIATION 8.7 • n=7 Participants	64.3 years STANDARD_DEVIATION 8.6 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	17 Participants n=7 Participants	33 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	25 Participants n=7 Participants	46 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	20 Participants n=5 Participants	26 Participants n=7 Participants	46 Participants n=5 Participants
Race (NIH/OMB) White	16 Participants n=5 Participants	14 Participants n=7 Participants	30 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: 56 weeks

Outcome measures

Measure	Spironolactone n=37 Participants Spironolactone Spironolactone: Patients will be given Spironolactone 12.5 mg on week 0 (visit 2). Patients will be escalated to 25 mg daily Spironolactone or maximal tolerated dose over a 4-week period. Patients will continue treatment for an additional 48 weeks.	Placebo n=42 Participants Placebo Placebo: Placebo
Percent Change in Atheroma Volume (PAV) in the Thoracic Aorta of Spironolactone vs. Placebo	0.5 percentage change Standard Deviation 10.3	7.3 percentage change Standard Deviation 11.4

SECONDARY outcome

Timeframe: 56 weeks

Outcome measures

Measure	Spironolactone n=37 Participants Spironolactone Spironolactone: Patients will be given Spironolactone 12.5 mg on week 0 (visit 2). Patients will be escalated to 25 mg daily Spironolactone or maximal tolerated dose over a 4-week period. Patients will continue treatment for an additional 48 weeks.	Placebo n=42 Participants Placebo Placebo: Placebo
Left Ventricular Mass Index of Spironolactone vs. Placebo.	-3.5 g/m^2 Standard Deviation 3.7	2.1 g/m^2 Standard Deviation 4.5

SECONDARY outcome

Timeframe: 56 weeks

Outcome measures

Measure	Spironolactone n=37 Participants Spironolactone Spironolactone: Patients will be given Spironolactone 12.5 mg on week 0 (visit 2). Patients will be escalated to 25 mg daily Spironolactone or maximal tolerated dose over a 4-week period. Patients will continue treatment for an additional 48 weeks.	Placebo n=42 Participants Placebo Placebo: Placebo
Myocardial Fibrosis (Change in Native T1) Spironolactone vs. Placebo	-10.3 ms Standard Deviation 35.9	17.1 ms Standard Deviation 35.6

SECONDARY outcome

Timeframe: 11 weeks

Outcome measures

Measure	Spironolactone n=37 Participants Spironolactone Spironolactone: Patients will be given Spironolactone 12.5 mg on week 0 (visit 2). Patients will be escalated to 25 mg daily Spironolactone or maximal tolerated dose over a 4-week period. Patients will continue treatment for an additional 48 weeks.	Placebo n=42 Participants Placebo Placebo: Placebo
Change in 24-hour Ambulatory Systolic Blood Pressure of Spironolactone vs. Placebo	-5.95 mmHg Standard Deviation 10.9	2 mmHg Standard Deviation 17.59

SECONDARY outcome

Timeframe: 56 weeks

Population: Data not collected for this outcome measure.

Outcome measures

Outcome data not reported

Adverse Events

Spironolactone

Serious events: 7 serious events

Other events: 9 other events

Deaths: 1 deaths

Placebo

Serious events: 8 serious events

Other events: 8 other events

Deaths: 1 deaths

Serious adverse events

Measure	Spironolactone n=37 participants at risk Spironolactone Spironolactone: Patients will be given Spironolactone 12.5 mg on week 0 (visit 2). Patients will be escalated to 25 mg daily Spironolactone or maximal tolerated dose over a 4-week period. Patients will continue treatment for an additional 48 weeks.	Placebo n=42 participants at risk Placebo Placebo: Placebo
Blood and lymphatic system disorders Hyperkalemia	2.7% 1/37 • Number of events 1 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.	0.00% 0/42 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.
Endocrine disorders Diabetes related	5.4% 2/37 • Number of events 2 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.	2.4% 1/42 • Number of events 1 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.
Infections and infestations Infection	5.4% 2/37 • Number of events 2 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.	4.8% 2/42 • Number of events 2 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.
Surgical and medical procedures Surgical	2.7% 1/37 • Number of events 1 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.	9.5% 4/42 • Number of events 4 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.
Cardiac disorders Chest pain/discomfort	2.7% 1/37 • Number of events 1 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.	0.00% 0/42 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.
Injury, poisoning and procedural complications Injury	0.00% 0/37 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.	2.4% 1/42 • Number of events 1 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.

Other adverse events

Measure	Spironolactone n=37 participants at risk Spironolactone Spironolactone: Patients will be given Spironolactone 12.5 mg on week 0 (visit 2). Patients will be escalated to 25 mg daily Spironolactone or maximal tolerated dose over a 4-week period. Patients will continue treatment for an additional 48 weeks.	Placebo n=42 participants at risk Placebo Placebo: Placebo
Blood and lymphatic system disorders Hyperkalemia	5.4% 2/37 • Number of events 2 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.	0.00% 0/42 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.
Blood and lymphatic system disorders Hypokalemia	0.00% 0/37 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.	4.8% 2/42 • Number of events 2 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.
Endocrine disorders Diabetes related	5.4% 2/37 • Number of events 2 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.	4.8% 2/42 • Number of events 2 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.
Cardiac disorders Hypotension	8.1% 3/37 • Number of events 3 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.	2.4% 1/42 • Number of events 1 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.
Renal and urinary disorders AKI	0.00% 0/37 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.	2.4% 1/42 • Number of events 1 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.
Cardiac disorders Chest pain/discomfort	2.7% 1/37 • Number of events 1 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.	0.00% 0/42 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.
General disorders Headache	0.00% 0/37 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.	2.4% 1/42 • Number of events 1 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.
General disorders Neck spasms	0.00% 0/37 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.	2.4% 1/42 • Number of events 1 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.
Reproductive system and breast disorders Breast tenderness/Gynecomastia	2.7% 1/37 • Number of events 1 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.	0.00% 0/42 • 12 months AEs were monitored by blood work, self report, vital signs, and MRI.

Additional Information

Dr. Sanjay Rajagopalan

University Hospitals Cleveland Medical Center

Phone: 216-844-5191

Email: Sanjay.Rajagopalan@uhhospitals.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place