Study of High-dose Spironolactone vs. Placebo Therapy in Acute Heart Failure (ATHENA-HF)

• ClinicalTrials.gov Identifier: NCT02235077
• Recruitment Status: Completed
• First Posted: September 9, 2014
• Results First Posted: May 17, 2017
• Last Update Posted: June 14, 2017
• Sponsor: Duke University
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Duke University

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Heart Failure
• Interventions: Drug: Spironolactone; Drug: Placebo
• Enrollment: 360

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Spironolactone	Placebo
Arm/Group Description	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.	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.
Period Title: Overall Study
Started	182	178
Completed	164	159
Not Completed	18	19
Reason Not Completed
Death	5	7
Lost to Follow-up	5	6
Withdrawal by Subject	8	5
Physician Decision	0	1

Baseline Characteristics

Arm/Group Title		Spironolactone	Placebo	Total
Arm/Group Description		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.	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.	Total of all reporting groups
Overall Number of Baseline Participants		182	178	360
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	182 participants	178 participants	360 participants
		65.9 (13.7)	63.5 (14.4)	64.7 (14.1)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	182 participants	178 participants	360 participants
	Female	65 35.7%	64 36.0%	129 35.8%
	Male	117 64.3%	114 64.0%	231 64.2%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	182 participants	178 participants	360 participants
	Hispanic or Latino	2 1.1%	6 3.4%	8 2.2%
	Not Hispanic or Latino	180 98.9%	172 96.6%	352 97.8%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	182 participants	178 participants	360 participants
	American Indian or Alaska Native	3 1.6%	1 0.6%	4 1.1%
	Asian	3 1.6%	1 0.6%	4 1.1%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	74 40.7%	77 43.3%	151 41.9%
	White	101 55.5%	99 55.6%	200 55.6%
	More than one race	1 0.5%	0 0.0%	1 0.3%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%

Outcome Measures

1. Primary Outcome

Title	96 Hour Change in NT-proBNP
Description	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.
Time Frame	Randomization to 96 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Spironolactone	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	182	178
Mean (Standard Deviation); Unit of Measure: log pg/ml
	-0.58 (0.69)	-0.61 (0.72)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Spironolactone, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5688
	Comments	[Not Specified]
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -0.11 to 0.20
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	96 Hour Change in Clinical Congestion Score
Description	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.
Time Frame	Randomization through 96 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Spironolactone	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	182	178
Mean (Standard Deviation); Unit of Measure: units on a scale
	-5.59 (3.34)	-5.82 (3.32)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Spironolactone, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4155
	Comments	[Not Specified]
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.25
	Confidence Interval	(2-Sided) 95%; -0.35 to 0.86
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	96 Hour Change in Dyspnea Likert Score
Description	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.
Time Frame	Randomization through 96 hours

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Spironolactone	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	166	163
Measure Type: Count of Participants; Unit of Measure: Participants
Markedly improved	64 38.6%	79 48.5%
Moderately improved	56 33.7%	39 23.9%
Minimally improved	24 14.5%	18 11.0%
No change	17 10.2%	21 12.9%
Minimally worse	4 2.4%	5 3.1%
Moderately worse	0 0.0%	0 0.0%
Markedly worse	1 0.6%	1 0.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Spironolactone, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3039
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.23
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.81
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	96 Hour Change in Serum Creatinine
Description	Renal function via serum creatinine, will be assessed at randomization and daily through 96 hours
Time Frame	Randomization through 96 hours

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Spironolactone	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	100	101
Mean (Standard Deviation); Unit of Measure: mg/dl
	0.15 (0.30)	0.16 (0.30)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Spironolactone, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7673
	Comments	[Not Specified]
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95%; -0.09 to 0.07
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	96 Hour Net Fluid Output
Description	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.
Time Frame	Randomization through 96 hours

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Spironolactone	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	87	96
Mean (Standard Deviation); Unit of Measure: ml
	5824 (4007)	5507 (3633)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Spironolactone, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5734
	Comments	[Not Specified]
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	319.2
	Confidence Interval	(2-Sided) 95%; -797.4 to 1435.8
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	96 Hour Change in Body Weight
Description	Baseline body weight assessment will be completed, and changes in weight documented daily through 96 hours or earlier discharge
Time Frame	Randomization through 96 hours or earlier discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Spironolactone	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	182	178
Mean (Standard Deviation); Unit of Measure: pounds
	-8.1 (10.7)	-7.5 (9.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Spironolactone, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3528
	Comments	[Not Specified]
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.02
	Confidence Interval	(2-Sided) 95%; -3.05 to 1.01
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	96 Hour Change in Serum Potassium Levels
Description	Change in serum potassium levels at 96 hours as compared to baseline.
Time Frame	Baseline, 96 hours

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Spironolactone	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	99	101
Mean (Standard Deviation); Unit of Measure: mEq/L
	0.31 (0.54)	0.15 (0.69)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Spironolactone, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0846
	Comments	[Not Specified]
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.11
	Confidence Interval	(2-Sided) 95%; -0.02 to 0.25
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Change in Loop Diuretics Requirements From Baseline to 30 Days
Description	Medications will be reviewed to assess loop diuretic dose requirements through Day 30 following randomization
Time Frame	Randomization through Day 30

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Spironolactone	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	164	158
Mean (Standard Deviation); Unit of Measure: mg
	19.66 (69.95)	30.70 (68.29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Spironolactone, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0842
	Comments	[Not Specified]
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-12.17
	Confidence Interval	(2-Sided) 95%; -25.98 to 1.65
	Estimation Comments	[Not Specified]

9. Secondary Outcome

Title	Presence of Outpatient Worsening Heart Failure Symptoms Through Day 30
Description	Outpatient worsening heart failure symptoms will be assessed from discharge through Day 30
Time Frame	Hospital discharge through Day 30

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Spironolactone	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	166	163
Measure Type: Count of Participants; Unit of Measure: Participants
	19 11.4%	17 10.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Spironolactone, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7628
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 95%; 0.56 to 2.23
	Estimation Comments	[Not Specified]

10. Secondary Outcome

Title	96 Hour Change in Dyspnea Visual Analog Scale
Description	Dyspnea visual analog scale change from randomization to 96 hours. Scale range 0-100 with 100 being the best possible score.
Time Frame	Randomization to 96 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Spironolactone	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	182	178
Mean (Standard Deviation); Unit of Measure: units on a scale
	17.2 (25.0)	17.9 (24.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Spironolactone, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6102
	Comments	[Not Specified]
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.04
	Confidence Interval	(2-Sided) 95%; -5.02 to 2.95
	Estimation Comments	[Not Specified]

11. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Spironolactone	Placebo
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	182	178
Measure Type: Count of Participants; Unit of Measure: Participants
	8 4.4%	10 5.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Spironolactone, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5818
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.76
	Confidence Interval	(2-Sided) 95%; 0.29 to 1.99
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form. Only Serious Adverse Events were collected on the data forms.
Adverse Event Reporting Description	Adverse event data was collected by the sites from randomization through 30 days, but was not collected on the case report form.
Arm/Group Title	Spironolactone		Placebo
Arm/Group Description	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.		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.
All-Cause Mortality
	Spironolactone		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	5/182 (2.75%)		7/178 (3.93%)
Serious Adverse Events
	Spironolactone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/182 (11.54%)		13/178 (7.30%)
Blood and lymphatic system disorders
Anaemia † 1	1/182 (0.55%)	1	0/178 (0.00%)	0
Cardiac disorders
Aortic valve stenosis † 1	1/182 (0.55%)	1	0/178 (0.00%)	0
Cardiogenic shock † 1	1/182 (0.55%)	1	0/178 (0.00%)	0
Gastrointestinal disorders
Gastrointestinal Haemmorhage † 1	1/182 (0.55%)	1	0/178 (0.00%)	0
Protalgia † 1	1/182 (0.55%)	1	0/178 (0.00%)	0
General disorders
Multi-organ failure † 1	1/182 (0.55%)	1	0/178 (0.00%)	0
Non-cardiac chest pain † 1	1/182 (0.55%)	1	0/178 (0.00%)	0
Systemic inflammatory response syndrome † 1	1/182 (0.55%)	1	0/178 (0.00%)	0
Infections and infestations
H1N1 Influenza † 1	1/182 (0.55%)	1	0/178 (0.00%)	0
Oesophageal Candidiasis † 1	0/182 (0.00%)	0	1/178 (0.56%)	1
Pneumonia † 1	3/182 (1.65%)	3	1/178 (0.56%)	1
Tooth abscess † 1	0/182 (0.00%)	0	1/178 (0.56%)	1
Urinary tract infection † 1	1/182 (0.55%)	1	0/178 (0.00%)	0
Injury, poisoning and procedural complications
Fall † 1	1/182 (0.55%)	1	1/178 (0.56%)	1
Post-procedural haemotoma † 1	0/182 (0.00%)	0	1/178 (0.56%)	1
Traumatic haemotoma † 1	1/182 (0.55%)	1	0/178 (0.00%)	0
Vascular pseudoaneurysm † 1	0/182 (0.00%)	0	1/178 (0.56%)	1
Investigations
International Normalised Ratio Increased † 1	1/182 (0.55%)	1	0/178 (0.00%)	0
Metabolism and nutrition disorders
Gout † 1	0/182 (0.00%)	0	1/178 (0.56%)	1
Hyperglycaemia † 1	1/182 (0.55%)	1	0/178 (0.00%)	0
Hypokalaemia † 1	1/182 (0.55%)	1	0/178 (0.00%)	0
Lactic acidosis † 1	1/182 (0.55%)	1	0/178 (0.00%)	0
Musculoskeletal and connective tissue disorders
Pain in extremity † 1	0/182 (0.00%)	0	1/178 (0.56%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon † 1	1/182 (0.55%)	1	0/178 (0.00%)	0
Basal cell carcinoma † 1	0/182 (0.00%)	0	1/178 (0.56%)	1
Nervous system disorders
Hepatic encephalopathy † 1	0/182 (0.00%)	0	1/178 (0.56%)	1
Partial seizures with secondary generalisation † 1	0/182 (0.00%)	0	1/178 (0.56%)	1
Psychiatric disorders
Delerium † 1	1/182 (0.55%)	1	0/178 (0.00%)	0
Psychogenic seizure † 1	0/182 (0.00%)	0	1/178 (0.56%)	1
Suicidal ideation † 1	0/182 (0.00%)	0	1/178 (0.56%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory failure † 1	4/182 (2.20%)	4	0/178 (0.00%)	0
Bronchial haemmorhage † 1	0/182 (0.00%)	0	1/178 (0.56%)	1
Chronic obstructive pulmonary disease † 1	1/182 (0.55%)	1	1/178 (0.56%)	1
Pneumonia aspiration † 1	1/182 (0.55%)	1	0/178 (0.00%)	0
Vascular disorders
Aortic dissection † 1	1/182 (0.55%)	1	0/178 (0.00%)	0
Distributive shock † 1	1/182 (0.55%)	1	0/178 (0.00%)	0
Hypertension † 1	0/182 (0.00%)	0	1/178 (0.56%)	1
Hypertensive crisis † 1	1/182 (0.55%)	1	0/178 (0.00%)	0
Hypertensive emergency † 1	2/182 (1.10%)	2	0/178 (0.00%)	0
Hypotension † 1	1/182 (0.55%)	1	0/178 (0.00%)	0
Hypovolaemic shock † 1	1/182 (0.55%)	1	0/178 (0.00%)	0
1 Term from vocabulary, MedDRA (Unspecified); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Spironolactone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0		0/0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

To minimize the probability of inaccurate data in published materials, it is the policy of the Heart Failure Network that all data and text considered for all papers, and all abstracts for presentation at scientific meetings be submitted to the Publication and Presentation Subcommittee, the NHLBI Project Officer, and the Coordinating Center for review and approval prior to presentation or publication.

Results Point of Contact

• Name/Title: Adrian Hernandez, MD
• Organization: Duke Clinical Research Institute
• Phone: 919 668 7515
• EMail: adrian.hernandez@duke.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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:CD007004. doi: 10.1002/14651858.CD007004.pub4.

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.

Butler J, Anstrom KJ, Felker GM, Givertz MM, Kalogeropoulos AP, Konstam MA, Mann DL, Margulies KB, McNulty SE, Mentz RJ, Redfield MM, Tang WHW, Whellan DJ, Shah M, Desvigne-Nickens P, Hernandez AF, Braunwald E; National Heart Lung and Blood Institute Heart Failure Clinical Research Network. Efficacy and Safety of Spironolactone in Acute Heart Failure: The ATHENA-HF Randomized Clinical Trial. JAMA Cardiol. 2017 Sep 1;2(9):950-958. doi: 10.1001/jamacardio.2017.2198.

Butler J, Hernandez AF, Anstrom KJ, Kalogeropoulos A, Redfield MM, Konstam MA, Tang WH, Felker GM, Shah MR, Braunwald E. Rationale and Design of the ATHENA-HF Trial: Aldosterone Targeted Neurohormonal Combined With Natriuresis Therapy in Heart Failure. JACC Heart Fail. 2016 Sep;4(9):726-35. doi: 10.1016/j.jchf.2016.06.003. Epub 2016 Aug 10.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT02235077
• Other Study ID Numbers: Pro00057090; 5U01HL084904 ( U.S. NIH Grant/Contract )
• First Submitted: September 3, 2014
• First Posted: September 9, 2014
• Results First Submitted: April 7, 2017
• Results First Posted: May 17, 2017
• Last Update Posted: June 14, 2017