Study of High-dose Spironolactone vs. Placebo Therapy in... | NCT02235077

ID	Type	Description	Link
5U01HL084904	U.S. NIH Grant/Contract		View source

Name	Class
National Heart, Lung, and Blood Institute (NHLBI)	NIH

Description Module

Detailed Description

Mineralocorticoid receptor antagonist (MRA) therapy is recommended in stable chronic systolic heart failure (HF) and post-infarction HF patients for improving morbidity and mortality. MRA therapy in AHF and in high doses is less well studied. The effectiveness and safety of early high dose MRA therapy in AHF is supported by a single-blind study showing lower risk of worsening renal function and need for loop diuretics, and improved congestion. MRA therapy in AHF may improve outcomes by relieving congestion at higher doses through their natriuretic property, in addition to preventing the deleterious effects of exacerbation of neuro-hormonal activation by loop diuretics.

This randomized, double blind, placebo-controlled study of high-dose spironolactone vs. placebo (for patients not receiving MRA at home) or low-dose spironolactone (for patients already receiving low-dose spironolactone) in AHF, will enroll 360 participants at approximately 30 clinical centers. After obtaining informed consent, subjects who fulfill all the inclusion criteria and none of the exclusion criteria will be randomized. Randomization will be performed by using procedures determined by the Coordinating Center (CC).

Patients receiving no MRA therapy at baseline will be randomized to receive either spironolactone 100 mg or placebo daily for 96 hours.
Patients already receiving low-dose spironolactone at baseline (12.5 mg or 25 mg daily) will be randomized to 100 mg or 25 mg spironolactone daily for 96 hours.

Within 24 hours prior to randomization, all study participants will undergo:

Medical History
Review of medications including pre-hospital loop diuretics, MRA, and potassium doses
Physical examination, vital signs and body weight
Measurement of creatinine, blood urea nitrogen (BUN), and electrolytes
Dyspnea Relief Assessments (7-point Likert and Visual Analog Scale)
Serum pregnancy test for all women of childbearing potential
Collection of samples for measurement of NT-proBNP levels (Core Lab)

Study drug will be initiated as follows:

Patients receiving no MRA therapy at baseline: 4x25 mg study capsules once daily; starting dose 100 mg spironolactone or placebo; if dose adjustment is required, active capsules will be adjusted by pharmacy to achieve the required dose.
Patients already receiving low-dose spironolactone at baseline: 4x25 mg study capsules once daily; one capsule containing 25 mg spironolactone and 3x25 mg study capsules containing spironolactone or placebo; if dose adjustment is required, active capsules will be adjusted by pharmacy to achieve the required dose.

Patients will be followed every 24 hours following randomization through 96 hours. Study drug will be administered daily for 96 hours. Study drug administration time is anchored to time of randomization. Dose adjustments (continue, hold, stop) are permitted according to serum K+ and renal function.

Assessment at 24 hours post randomization includes: Review of medications, body weight, fluid intake/urine output, creatinine, blood urea nitrogen (BUN), and electrolytes, and adverse events.

If the 24 hour assessment is also the day of discharge, include:

Physical exam / Vital signs
Dyspnea Relief (7-Point Likert and VAS) worksheets
Biomarkers (NT-proBNP) (Core Lab)

Assessment at 48 hours post randomization includes: Review of medications, physical exam/vital signs, body weight, fluid intake/urine output, Dyspnea Relief (7-Point Likert and VAS) worksheets, creatinine, blood urea nitrogen (BUN), and electrolytes, biomarker levels (NT-proBNP) by Core Lab.

Assessment at 72 hours post randomization includes: Review of medications, body weight, fluid intake/urine output, creatinine, blood urea nitrogen (BUN), and electrolytes, and adverse events.

If the 72 hour assessment is also the day of discharge, include:

Physical exam / Vital signs
Dyspnea Relief (7-Point Likert and VAS) worksheets
Biomarkers (NT-proBNP) (Core Lab)

Assessment at 96 hours post randomization includes: Review of medications, physical exam/vital signs, body weight, fluid intake/urine output, creatinine, blood urea nitrogen (BUN), and electrolytes, Dyspnea Relief (7-Point Likert and VAS), and biomarker levels (NT-proBNP) by Core Lab.

If patient is clinically euvolemic in less than 96 hours, the investigator may consider changing loop diuretics to oral dose.

Study drug will be discontinued after 96 hours and further use of MRA will be left to the treating physician's discretion.

Assessment at Discharge: If discharge occurs after the 96 hour assessment but prior to the 30 day follow-up telephone call,the following will be documented: Medication review (prescribed medications at the time of discharge), body weight (if available), creatinine, blood urea nitrogen (BUN), and electrolytes (if available), and adverse events.

Ejection fraction data will be obtained from echocardiogram within 6 months prior to randomization. Those patients who do not have an echocardiogram recorded within this time frame will get an echocardiogram, nuclear perfusion study, MRI, or MUGA performed prior to the 96 hour in-hospital assessment to ascertain ejection fraction.

Follow-up Telephone Call at Day 30: All participants will be contacted by telephone at day 30 (+3 days) following randomization to assess tertiary endpoints, including medication use and adverse events.

Follow-up Telephone Call at Day 60: All participants will be contacted by telephone at day 60 (+/-3 days) following randomization to assess vital status.

During the consent process, patients will be asked if interested in donating samples and data for research purposes via a biorepository and/or genetic study. Based on site and IRB preference, this optional part of the study may be incorporated into the main consent or may be a separate consent and IRB application.

Label	Type	Description	Intervention Names
Spironolactone	Active Comparator	Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours	Drug: Spironolactone
Placebo	Placebo Comparator	Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Spironolactone	Drug	Patients receiving no MRA at home will receive spironolactone 100 mg (4x25 mg capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will be randomized to receive spironolactone 25 mg (1x25 mg capsules) or 100 mg (4x25 mg capsules) in hospital for 96 hours. The patients who are randomized to 25 mg spironolactone will also receive 75 mg placebo (3x25 mg capsules) in order to maintain blinding.

Measure	Description	Time Frame
96 Hour Change in NT-proBNP	The Core Laboratory at Vermont will determine NT-proBNP levels for calculation of the endpoint from samples obtained at randomization and 96 hours respectively. NT-proBNP was converted to log scale.	Randomization to 96 hours

Measure	Description	Time Frame
96 Hour Change in Clinical Congestion Score	Clinical congestion score will be assessed at randomization, 96 hours, and at discharge. Scale consisted of sum of six signs and symptoms of congestion, each scored 0-3. Zero indicates no sign/symptom and 3 indicates worst case of sign/symptom. Score range 0-18 with 18 being worst score.	Randomization through 96 hours

Measure	Description	Time Frame
Day 60 Mortality	All participants will be contacted by telephone at 60 days, +/- 3 days post randomization to assess vital status (death).	60 days post randomization

Name	Affiliation	Role
Adrian Hernandez, MD	Duke University Health Systems	Principal Investigator
Eugene Braunwald, MD	Harvard University	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Emory University School of Medicine		Atlanta	Georgia	30322	United States
Johns Hopkins Hospital

PubMed Identifier	Type	Citation	Retractions
33107592	Derived	Chung EY, Ruospo M, Natale P, Bolignano D, Navaneethan SD, Palmer SC, Strippoli GF. Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2020 Oct 27;10(10):CD007004. doi: 10.1002/14651858.CD007004.pub4.
31230825	Derived	Greene SJ, Felker GM, Giczewska A, Kalogeropoulos AP, Ambrosy AP, Chakraborty H, DeVore AD, Fudim M, McNulty SE, Mentz RJ, Vaduganathan M, Hernandez AF, Butler J. Spironolactone in Acute Heart Failure Patients With Renal Dysfunction and Risk Factors for Diuretic Resistance: From the ATHENA-HF Trial. Can J Cardiol. 2019 Sep;35(9):1097-1105. doi: 10.1016/j.cjca.2019.01.022. Epub 2019 Feb 7.

ID	Title	Description
FG000	Spironolactone	Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

96 Hour Change in NT-proBNP

The Core Laboratory at Vermont will determine NT-proBNP levels for calculation of the endpoint from samples obtained at randomization and 96 hours respectively. NT-proBNP was converted to log scale.

Posted

Mean

Standard Deviation

log pg/ml

Randomization to 96 hours

ID	Title	Description
OG000	Spironolactone	Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
OG001	Placebo	Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.

Units	Counts
Participants	OG000182 OG001178

Title

Denominators

Categories

Title	Measurements
	OG000-0.58± 0.69 OG001-0.61± 0.72

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Regression, Linear		0.5688		Mean Difference (Final Values)	0.05			2-Sided	95	-0.11	0.20					Superiority

Secondary

96 Hour Change in Clinical Congestion Score

Clinical congestion score will be assessed at randomization, 96 hours, and at discharge. Scale consisted of sum of six signs and symptoms of congestion, each scored 0-3. Zero indicates no sign/symptom and 3 indicates worst case of sign/symptom. Score range 0-18 with 18 being worst score.

Posted

Mean

Standard Deviation

units on a scale

Randomization through 96 hours

ID	Title	Description
OG000	Spironolactone	Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
OG001	Placebo	Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.

Secondary

96 Hour Change in Dyspnea Likert Score

Dyspnea relief via 7-point Likert scale will be assessed at randomization, 96 hours, and at discharge. The Likert score was defined as 1=markedly improved, 2=moderately improved, 3=minimally improved; 4=no change, 5=minimally worse, 6=moderately worse, and 7=markedly worse as compared with the degree of dyspnea present at randomization.

All data for completed assessments was analyzed. For outcomes where the number of participants analyzed is less than 182 spironolactone / 178 placebo, the number of subjects analyzed represents the number of subjects for whom the data was collected.

Posted

Count of Participants

Participants

Randomization through 96 hours

ID	Title	Description
OG000	Spironolactone	Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
OG001	Placebo	Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.

Secondary

96 Hour Change in Serum Creatinine

Renal function via serum creatinine, will be assessed at randomization and daily through 96 hours

Posted

Mean

Standard Deviation

mg/dl

Randomization through 96 hours

ID	Title	Description
OG000	Spironolactone	Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
OG001	Placebo	Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.

Secondary

96 Hour Net Fluid Output

Fluid intake and urine output will be assessed daily while in hospital through 96 hours. Net fluid output (output minus input) through 96 hours is reported.

Posted

Mean

Standard Deviation

Randomization through 96 hours

ID	Title	Description
OG000	Spironolactone	Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
OG001	Placebo	Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.

Secondary

96 Hour Change in Body Weight

Baseline body weight assessment will be completed, and changes in weight documented daily through 96 hours or earlier discharge

Posted

Mean

Standard Deviation

pounds

Randomization through 96 hours or earlier discharge

ID	Title	Description
OG000	Spironolactone	Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
OG001	Placebo	Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.

Units	Counts
Participants

Secondary

96 Hour Change in Serum Potassium Levels

Change in serum potassium levels at 96 hours as compared to baseline.

Posted

Mean

Standard Deviation

mEq/L

Baseline, 96 hours

ID	Title	Description
OG000	Spironolactone	Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
OG001	Placebo	Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.

Secondary

Change in Loop Diuretics Requirements From Baseline to 30 Days

Medications will be reviewed to assess loop diuretic dose requirements through Day 30 following randomization

Posted

Mean

Standard Deviation

Randomization through Day 30

ID	Title	Description
OG000	Spironolactone	Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
OG001	Placebo	Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.

Secondary

Presence of Outpatient Worsening Heart Failure Symptoms Through Day 30

Outpatient worsening heart failure symptoms will be assessed from discharge through Day 30

Posted

Count of Participants

Participants

Hospital discharge through Day 30

ID	Title	Description
OG000	Spironolactone	Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
OG001	Placebo	Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.

Secondary

96 Hour Change in Dyspnea Visual Analog Scale

Dyspnea visual analog scale change from randomization to 96 hours. Scale range 0-100 with 100 being the best possible score.

Posted

Mean

Standard Deviation

units on a scale

Randomization to 96 hours

ID	Title	Description
OG000	Spironolactone	Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
OG001	Placebo	Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.

Units	Counts
Participants

Other Pre-specified

Day 60 Mortality

All participants will be contacted by telephone at 60 days, +/- 3 days post randomization to assess vital status (death).

Posted

Count of Participants

Participants

60 days post randomization

ID	Title	Description
OG000	Spironolactone	Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
OG001	Placebo	Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected182 at risk EG0010 events0 affected178 at risk
Aortic valve stenosis	Cardiac disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected182 at risk EG0010 events0 affected178 at risk
Cardiogenic shock	Cardiac disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected182 at risk EG0010 events0 affected178 at risk
Gastrointestinal Haemmorhage	Gastrointestinal disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected182 at risk EG0010 events0 affected178 at risk
Protalgia	Gastrointestinal disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected182 at risk EG0010 events0 affected178 at risk
Multi-organ failure	General disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected182 at risk EG0010 events0 affected178 at risk
Non-cardiac chest pain	General disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected182 at risk EG0010 events0 affected178 at risk
Systemic inflammatory response syndrome	General disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected182 at risk EG0010 events0 affected178 at risk
H1N1 Influenza	Infections and infestations	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected182 at risk EG0010 events0 affected178 at risk
Oesophageal Candidiasis	Infections and infestations	MedDRA (Unspecified)	Systematic Assessment	EG0000 events0 affected182 at risk EG0011 events1 affected178 at risk
Pneumonia	Infections and infestations	MedDRA (Unspecified)	Systematic Assessment	EG0003 events3 affected182 at risk EG0011 events1 affected178 at risk
Tooth abscess	Infections and infestations	MedDRA (Unspecified)	Systematic Assessment	EG0000 events0 affected182 at risk EG0011 events1 affected178 at risk
Urinary tract infection	Infections and infestations	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected182 at risk EG0010 events0 affected178 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected182 at risk EG0011 events1 affected178 at risk
Post-procedural haemotoma	Injury, poisoning and procedural complications	MedDRA (Unspecified)	Systematic Assessment	EG0000 events0 affected182 at risk EG0011 events1 affected178 at risk
Traumatic haemotoma	Injury, poisoning and procedural complications	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected182 at risk EG0010 events0 affected178 at risk
Vascular pseudoaneurysm	Injury, poisoning and procedural complications	MedDRA (Unspecified)	Systematic Assessment	EG0000 events0 affected182 at risk EG0011 events1 affected178 at risk
International Normalised Ratio Increased	Investigations	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected182 at risk EG0010 events0 affected178 at risk
Gout	Metabolism and nutrition disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 events0 affected182 at risk EG0011 events1 affected178 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected182 at risk EG0010 events0 affected178 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected182 at risk EG0010 events0 affected178 at risk
Lactic acidosis	Metabolism and nutrition disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected182 at risk EG0010 events0 affected178 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 events0 affected182 at risk EG0011 events1 affected178 at risk
Adenocarcinoma of colon	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected182 at risk EG0010 events0 affected178 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (Unspecified)	Systematic Assessment	EG0000 events0 affected182 at risk EG0011 events1 affected178 at risk
Hepatic encephalopathy	Nervous system disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 events0 affected182 at risk EG0011 events1 affected178 at risk
Partial seizures with secondary generalisation	Nervous system disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 events0 affected182 at risk EG0011 events1 affected178 at risk
Delerium	Psychiatric disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected182 at risk EG0010 events0 affected178 at risk
Psychogenic seizure	Psychiatric disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 events0 affected182 at risk EG0011 events1 affected178 at risk
Suicidal ideation	Psychiatric disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 events0 affected182 at risk EG0011 events1 affected178 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (Unspecified)	Systematic Assessment	EG0004 events4 affected182 at risk EG0010 events0 affected178 at risk
Bronchial haemmorhage	Respiratory, thoracic and mediastinal disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 events0 affected182 at risk EG0011 events1 affected178 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected182 at risk EG0011 events1 affected178 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected182 at risk EG0010 events0 affected178 at risk
Aortic dissection	Vascular disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected182 at risk EG0010 events0 affected178 at risk
Distributive shock	Vascular disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected182 at risk EG0010 events0 affected178 at risk
Hypertension	Vascular disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 events0 affected182 at risk EG0011 events1 affected178 at risk
Hypertensive crisis	Vascular disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected182 at risk EG0010 events0 affected178 at risk
Hypertensive emergency	Vascular disorders	MedDRA (Unspecified)	Systematic Assessment	EG0002 events2 affected182 at risk EG0010 events0 affected178 at risk
Hypotension	Vascular disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected182 at risk EG0010 events0 affected178 at risk
Hypovolaemic shock	Vascular disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected182 at risk EG0010 events0 affected178 at risk

ID	Term
D006333	Heart Failure
D006331	Heart Diseases
D002318	Cardiovascular Diseases

ID	Term
D007783	Lactones
D009930	Organic Chemicals
D011283	Pregnenes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds

ID	Title	Description
BG000	Spironolactone	Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
BG001	Placebo	Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Spironolactone	Spironolactone 25mg or 100 mg orally, once daily while in the hospital for 96 hours Spironolactone: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.	5	182	21	182	0	0
EG001	Placebo	Placebo 25mg or 100mg orally, once daily while in the hospital for 96 hours Placebo: Patients receiving no MRA at home will receive either spironolactone 100 mg or matching placebo (4x25 mg study capsules) once daily for 96 hours. Patients already receiving low-dose MRA at home will receive spironolactone 100 mg vs. 25 mg (1x25 mg spironolactone and 3 placebo study capsules) in hospital for 96 hours.	7	178	13	178	0	0