Trial Outcomes & Findings for Antiarrhythmic Effects of Spironolactone in Patients With ICDs (NCT NCT04495712)

Results Overview

Time to first documented ICD therapy for ventricular tachycardia or ventricular fibrillation after randomization

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

90 participants

Primary outcome timeframe

through study completion, an average of 35 months

Results posted on

2020-10-09

Participant Flow

Participant milestones

Participant milestones
Measure	Spironolactone Patients randomized to active therapy with spironolactone spironolactone: aldosterone blocker	Placebo patients randomized to placebo placebo: identical in appearance to spironolactone study drug
Overall Study STARTED	44	46
Overall Study COMPLETED	44	46
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Spironolactone n=44 Participants Patients randomized to active therapy with spironolactone spironolactone: aldosterone blocker	Placebo n=46 Participants patients randomized to placebo placebo: identical in appearance to spironolactone study drug	Total n=90 Participants Total of all reporting groups
Age, Continuous	66.6 years STANDARD_DEVIATION 10.9 • n=44 Participants	66.5 years STANDARD_DEVIATION 9.3 • n=46 Participants	66.5 years STANDARD_DEVIATION 10.0 • n=90 Participants
Sex: Female, Male Female	44 Participants n=44 Participants	42 Participants n=46 Participants	86 Participants n=90 Participants
Sex: Female, Male Male	0 Participants n=44 Participants	4 Participants n=46 Participants	4 Participants n=90 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United States	44 Participants n=44 Participants	46 Participants n=46 Participants	90 Participants n=90 Participants

PRIMARY outcome

Timeframe: through study completion, an average of 35 months

Population: all enrolled patients

Time to first documented ICD therapy for ventricular tachycardia or ventricular fibrillation after randomization

Outcome measures

Outcome measures
Measure	Spironolactone n=44 Participants Patients randomized to active therapy with spironolactone spironolactone: aldosterone blocker	Placebo n=46 Participants patients randomized to placebo placebo: identical in appearance to spironolactone study drug
Time to First Appropriate Implantable Cardioverter Defibrillator (ICD) Therapy	8.8 months Interval 0.0 to 37.2	12.3 months Interval 0.3 to 38.5

SECONDARY outcome

Timeframe: through study completion, an average of 35 months

Population: all randomized patients

Number of patients hospitalized for any reason during study follow-up.

Outcome measures

Outcome measures
Measure	Spironolactone n=44 Participants Patients randomized to active therapy with spironolactone spironolactone: aldosterone blocker	Placebo n=46 Participants patients randomized to placebo placebo: identical in appearance to spironolactone study drug
All Cause Hospitalization	28 Participants	24 Participants

SECONDARY outcome

Timeframe: measured 3 months after randomization

Population: Patients randomized at the Portland VA Hospital that consented to testing

The right ventricular effective refractory period (ERP) will be measured at 3 month in patients enrolled at the Portland VA Medical Center by single extra stimuli via their implanted defibrillator. The ERP is defined as the shortest paced beat coupling interval that fails to produce ventricular capture after a baseline stable pacing train.

Outcome measures

Outcome measures
Measure	Spironolactone n=12 Participants Patients randomized to active therapy with spironolactone spironolactone: aldosterone blocker	Placebo n=13 Participants patients randomized to placebo placebo: identical in appearance to spironolactone study drug
Ventricular Refractoriness	294.2 milliseconds Standard Deviation 40.8	278.3 milliseconds Standard Deviation 24.1

SECONDARY outcome

Timeframe: 12 months after enrollment

Short Form Health Survey adapted for veterans (SF36V) is a 36 item questionnaire that measures general physical and mental health \[17\]. The SF36V is a reliable and valid questionnaire, containing eight constructs of health status: physical functioning (PF), role limitations due to physical problems (RP), bodily pain (BP), general health perceptions (GH), energy/vitality (VT), social functioning (SF), role limitations due to emotional problems (RE), and mental health (MH). These eight dimensions can be summarized numerically into two scores, the physical component summary (PCS) and the mental component summary (MCS). Range 0-100 higher score is better Health Related Quality of Life (HRQOL). We are reporting the Mental Component Summary score at 12 months here.

Outcome measures

Outcome measures
Measure	Spironolactone n=44 Participants Patients randomized to active therapy with spironolactone spironolactone: aldosterone blocker	Placebo n=46 Participants patients randomized to placebo placebo: identical in appearance to spironolactone study drug
Short Form Health Survey Adapted for Veterans (SF36V)	54.87 score on a scale Standard Deviation 22.50	63.31 score on a scale Standard Deviation 20.35

SECONDARY outcome

Timeframe: 12 months

Patient Concerns Assessment (PCA) is a symptom checklist that measures physical symptoms and fears that are common after ICD implantation. The PCA is a disease-specific instrument for ICD QOL, symptoms, and distress, with a reliability of ( = 0.88). Range 0-44, a higher score reflects more concerns and fears.

Outcome measures

Outcome measures
Measure	Spironolactone n=44 Participants Patients randomized to active therapy with spironolactone spironolactone: aldosterone blocker	Placebo n=46 Participants patients randomized to placebo placebo: identical in appearance to spironolactone study drug
Patient Concerns Assessment (PCA)	22.15 score on a scale Standard Deviation 12.28	18.42 score on a scale Standard Deviation 10.06

SECONDARY outcome

Timeframe: through study completion, an average of 35 months

Kansas City Cardiomyopathy Questionnaire (KCCQ) is a 23-item reliable and valid questionnaire, which evaluates HRQOL in heart failure. It quantifies, in a disease-specific fashion, physical limitations, symptoms, quality of life, social interference and self-efficacy. KCCQ provides the calculation of 2 main scores, the overall score and the clinical summary score, which includes functional status, social limitation and quality of life domains scores. Range 0-100, higher scores represent higher HRQOL.

Outcome measures

Outcome measures
Measure	Spironolactone n=44 Participants Patients randomized to active therapy with spironolactone spironolactone: aldosterone blocker	Placebo n=46 Participants patients randomized to placebo placebo: identical in appearance to spironolactone study drug
Kansas City Cardiomyopathy Questionnaire (KCCQ)	57.35 score on a scale Standard Deviation 28.59	68.67 score on a scale Standard Deviation 22.55

Adverse Events

Spironolactone

Serious events: 39 serious events

Other events: 44 other events

Deaths: 13 deaths

Placebo

Serious events: 37 serious events

Other events: 46 other events

Deaths: 12 deaths

Serious adverse events

Serious adverse events
Measure	Spironolactone n=44 participants at risk Patients randomized to active therapy with spironolactone spironolactone: aldosterone blocker	Placebo n=46 participants at risk patients randomized to placebo placebo: identical in appearance to spironolactone study drug
General disorders hospitalization	86.4% 38/44 • life of the study mean 35 months	76.1% 35/46 • life of the study mean 35 months
General disorders death	29.5% 13/44 • life of the study mean 35 months	26.1% 12/46 • life of the study mean 35 months

Other adverse events

Other adverse events
Measure	Spironolactone n=44 participants at risk Patients randomized to active therapy with spironolactone spironolactone: aldosterone blocker	Placebo n=46 participants at risk patients randomized to placebo placebo: identical in appearance to spironolactone study drug
Endocrine disorders Gynecomastia	9.1% 4/44 • life of the study mean 35 months	0.00% 0/46 • life of the study mean 35 months
Cardiac disorders congestive heart failure	77.3% 34/44 • life of the study mean 35 months	71.7% 33/46 • life of the study mean 35 months
Renal and urinary disorders Prerenal azotemia	36.4% 16/44 • life of the study mean 35 months	23.9% 11/46 • life of the study mean 35 months
Gastrointestinal disorders Any gastrointestinal issue	56.8% 25/44 • life of the study mean 35 months	47.8% 22/46 • life of the study mean 35 months

Additional Information

Merritt Raitt MD

VA Portland Health Care System

Phone: 503-220-8262

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place