PEARL-HF: Evaluation of Patiromer in Heart Failure Patients

• Sponsor: Relypsa, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00868439
• Collaborator: Medpace, Inc. (Industry)
• Enrollment: 120
• Locations: 33
• Arms: 2
• Duration (Months): 8
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study was to assess the effects of patiromer on serum potassium participants with heart failure. This study also assessed the safety and tolerability of patiromer in participants with heart failure.

Condition or Disease	Intervention/Treatment	Phase
Hyperkalemia; Heart Failure	Drug: patiromer; Drug: placebo	Phase 2

Detailed Description

This was a double-blind, randomized, placebo-controlled, parallel-group, multiple-dose study in congestive heart failure participants. Depending on the outcome from the initial cohort of 100 participants (Part 1), a second cohort of 170 participants could have been enrolled (Part 2). Based on the results of Part 1 of the study, Part 2 was not conducted.

Participants were randomly assigned to and received patiromer (30 g/day) or placebo for up to 28 days. All participants also received spironolactone; the initial spironolactone dose was 25 mg daily and was increased to 50 mg daily for participants who had a serum potassium ≤ 5.1 mEq/L on treatment Day 14. Study visits occurred on treatment Days 3, 7, 14, 17, 21 and 28. A safety follow-up contact was made 7 days after administration of last dose of study drug.

Study Design

• Study Type: Interventional
• Actual Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Multicenter, Randomized, Double-blind, Placebo-Controlled, Parallel-Group, Multiple-Dose Study to Evaluate the Effects of Patiromer in Heart Failure Patients
• Study Start Date: Apr 1, 2009
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: patiromer	Drug: patiromer; Active investigational drug; Other Names: RLY5016 Veltassa
Placebo Comparator: placebo	Drug: placebo; placebo

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Serum Potassium to the End of the 28-day Treatment Period. [Baseline and Day 28]

Secondary Outcome Measures

1. Proportion of Participants With a Serum Potassium Level During the 28-day Treatment Period That Was > 5.5 mEq/L. [28 Days]

   Analysis based on central laboratory data.

2. Proportion of Participants Discontinuing the Study Due to Serum Potassium Elevation (Serum K+ > 5.5 mEq/L). [28 Days]

   Analysis based on local laboratory data.

3. Proportion of Participants Whose Spironolactone Dose Was Increased. [28 Days]

4. Proportion of Participants With an Increase in Serum Potassium Level From Baseline to the End of the 28-day Treatment Period That Was ≥ 0.5 mEq/L [Baseline and Day 28]

5. Time to First Elevated Serum K+ > 5.5 mEq/L. [28 Days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants with chronic heart failure clinically indicated to receive spironolactone therapy, aged 18 years or older with serum potassium level of 4.3 - 5.1 mEq/L at screening and baseline, AND (1) chronic kidney disease (GFR < 60 mL/min) OR (2) documented history of hyperkalemia within the last 6 months

• Females of child-bearing potential must be non-lactating, must have a negative serum pregnancy test at screening, and must have used a highly effective form of contraception for at least 3 months before study drug administration, during the study, and for one month after study completion

• Male participants and/or their female partners of child-bearing potential must use a highly effective form of contraception during the study and for 3 months after study completion

• Must sign informed consent document

Exclusion Criteria:

• History of bowel obstruction, swallowing disorders, severe gastrointestinal disorders or major gastrointestinal surgery

• Uncorrected hemodynamically significant primary valvular disease, known obstructive or restrictive cardiomyopathy, uncontrolled or hemodynamically unstable arrhythmia

• Coronary-artery bypass graft, percutaneous intervention (e.g. cardiac, cerebrovascular, aortic), or major surgery including thoracic and cardiac, within 3 months prior to baseline or anticipated need during study participation

• Heart transplant recipient, or anticipated need for transplant during study participation

• Any of the following events having occurred within 3 months prior to baseline: unstable angina as judged by the Investigator, unresolved acute coronary syndrome, transient ischemic attack or stroke

• Current dialysis participant, or anticipated need for dialysis during study participation

• Prior kidney transplant, or anticipated need for transplant during study participation

• Metastatic, late-stage or end-stage cancer with < 12 months life expectancy

• History of alcoholism or drug/chemical abuse within 1 year

• QTcB interval > 500 msec (Bazett's correction formula)

• Sustained systolic blood pressure > 170 or < 90 mmHg

• Liver enzymes (ALT, AST) > 3 times upper limit of normal

• Use of oral cardiac medications (including loop and thiazide diuretics) that have not been stable for at least 21 days prior to baseline and are not anticipated to remain stable during study participation

• Use of any IV cardiac medications within 21 days prior to baseline, or their anticipated need during study participation.

• Current use of polymer-based drugs (e.g. Renagel, Kayexalate, Welchol, Colestid), other phosphate binders or potassium binders, calcium supplements, antacids (eg TUMS, Maalox), or their anticipated need during study participation

• Use of aldosterone antagonist in the last 30 days prior to baseline, unless was discontinued due to hyperkalemia

• Use of potassium sparing medication and/or potassium supplements in the last 30 days prior to baseline

• Use of any investigational medication, 30 days or 5 half-lives whichever is longer, prior to baseline

• Participants who have taken investigational product in this study, or a previous patiromer study

• Inability to consume the study medication, or, in the opinion of the Investigator, inability to comply with the protocol

• In the opinion of the Investigator, any medical condition, uncontrolled systemic disease, serious intercurrent illness, or extenuating circumstance occurring or persisting, within 30 days prior to baseline, that would significantly decrease study compliance or jeopardize the safety of the participant or affect the validity of the trial results

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigator Site 029	Miami	Florida	United States	33176
2	Investigator Site 031	Port Charlotte	Florida	United States	33952
3	Investigator Site 009	Peoria	Illinois	United States	61606
4	Investigator Site 018	Minneapolis	Minnesota	United States	55417
5	Investigator Site 020	Buffalo	New York	United States	14215
6	Investigator Site 005	Northport	New York	United States	11768
7	Investigator Site 022	Columbus	Ohio	United States	43210
8	Investigator Site 001	Dallas	Texas	United States	75216
9	Investigator Site 019	Salt Lake City	Utah	United States	84124
10	Investigator Site 102	Brno		Czechia	62500
11	Investigator Site 104	Prague		Czechia	12008
12	Investigator Site 103	Prague		Czechia	14021
13	Investigator Site 605	Tbilisi		Georgia	0102
14	Investigator Site 602	Tbilisi		Georgia	0159
15	Investigator Site 604	Tbilisi		Georgia	0164
16	Investigator Site 603	Tbilisi		Georgia	0179
17	Investigator Site 201	Gottingen		Germany	37075
18	Investigator Site 202	Heidelberg		Germany	69120
19	Investigator Site 305	Warsaw		Poland	02637
20	Investigator Site 409	Barnaul		Russian Federation	656099
21	Investigator Site 407	Kemerovo		Russian Federation	650002
22	Investigator Site 406	Moscow		Russian Federation	111020
23	Investigator Site 402	Moscow		Russian Federation	111539
24	Investigator Site 403	Moscow		Russian Federation	129301
25	Investigator Site 404	St Petersburg		Russian Federation	197341
26	Investigator Site 412	St Petersburg		Russian Federation	198205
27	Investigator Site 405	St Petersburg		Russian Federation	199106
28	Investigator Site 507	Dnipropetrovsk		Ukraine	49023
29	Investigator Site 502	Kharkiv		Ukraine	61018
30	Investigator Site 509	Kharkiv		Ukraine	61176
31	Investigator Site 504	Kiev		Ukraine	03680
32	Investigator Site 506	Kiev		Ukraine	03680
33	Investigator Site 501	Kiev		Ukraine	04114

Sponsors and Collaborators

• Relypsa, Inc.
• Medpace, Inc.

Investigators

• Study Director: Director Clinical Operations, Relypsa, Inc.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Relypsa company website

Publications

None provided.

• Responsible Party: Relypsa, Inc.
• ClinicalTrials.gov Identifier: NCT00868439
• Other Study ID Numbers: RLY5016-202
• First Posted: Mar 25, 2009
• Last Update Posted: Jun 2, 2021
• Last Verified: May 1, 2021

• Keywords provided by Relypsa, Inc.: HF; Heart failure; hyperkalemia; chronic kidney disease; prevention of hyperkalemia in heart failure participants
• Additional relevant MeSH terms: Heart Failure; Hyperkalemia

Study Results

Participant Flow

Recruitment Details	120 subjects were randomized in Part 1 of the study (60 to each treatment group). Of these, 120 randomized subjects, 105 received either RLY5016 Powder for Suspension (n = 56) or placebo (n = 49).
Pre-assignment Detail	Eligible participants ≥ 18 y/o, had history of chronic HF, clinically initiated spironolactone therapy, serum K+ = 4.3 - 5.1 mEq/L at screening and baseline, and either had 1) CKD, w/ eGFR < 60 mL/min and receiving HF therapies or 2) documented history of hyperkalemia led to discontinuation w/ aldosterone antagonist w/in 6 months prior to baseline.

Arm/Group Title	Patiromer	Placebo
Arm/Group Description	Spironolactone + Patiromer Participants received patiromer (15 g twice daily [BID]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was > 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was > 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or > 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.	Spironolactone + Placebo Participants received placebo (twice daily [BID]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was > 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was > 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or > 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.
Period Title: Overall Study
STARTED	56	49
COMPLETED	48	40
NOT COMPLETED	8	9

Baseline Characteristics

Arm/Group Title	Patiromer	Placebo	Total
Arm/Group Description	Spironolactone + Patiromer Participants received patiromer (15 g twice daily [BID]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was > 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was > 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or > 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.	Spironolactone + Placebo Participants received placebo (twice daily [BID]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was > 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was > 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or > 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.	Total of all reporting groups
Overall Participants	55	49	104
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	16 29.1%	14 28.6%	30 28.8%
>=65 years	39 70.9%	35 71.4%	74 71.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.3 (8.66)	68.2 (10.46)	68.3 (9.50)
Sex: Female, Male (Count of Participants)
Female	26 47.3%	15 30.6%	41 39.4%
Male	29 52.7%	34 69.4%	63 60.6%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Serum Potassium to the End of the 28-day Treatment Period.
Time Frame	Baseline and Day 28

Outcome Measure Data

Analysis Population Description

Analysis was determined using Last Observation Carried Forward (LOCF).

Arm/Group Title	Patiromer	Placebo
Arm/Group Description	Spironolactone + Patiromer Participants received patiromer (15 g twice daily [BID]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was > 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was > 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or > 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.	Spironolactone + Placebo Participants received placebo (twice daily [BID]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was > 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was > 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or > 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.
Measure Participants	55	49
Least Squares Mean (Standard Error) [mEq/L]	-0.21 (0.066)	0.23 (0.072)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Patiromer, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	Proportion of Participants With a Serum Potassium Level During the 28-day Treatment Period That Was > 5.5 mEq/L.
Description	Analysis based on central laboratory data.
Time Frame	28 Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patiromer	Placebo
Arm/Group Description	Spironolactone + Patiromer Participants received patiromer (15 g twice daily [BID]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was > 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was > 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or > 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.	Spironolactone + Placebo Participants received placebo (twice daily [BID]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was > 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was > 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or > 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.
Measure Participants	55	49
Number [percentage of participants]	7.3 13.3%	24.5 50%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Patiromer, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	= 0.027
	Comments
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Proportion of Participants Discontinuing the Study Due to Serum Potassium Elevation (Serum K+ > 5.5 mEq/L).
Description	Analysis based on local laboratory data.
Time Frame	28 Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patiromer	Placebo
Arm/Group Description	Spironolactone + Patiromer Participants received patiromer (15 g twice daily [BID]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was > 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was > 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or > 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.	Spironolactone + Placebo Participants received placebo (twice daily [BID]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was > 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was > 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or > 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.
Measure Participants	55	49
Number [percentage of participants]	0 0%	6.1 12.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Patiromer, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	= 0.101
	Comments
	Method	Fisher Exact
	Comments

4. Secondary Outcome

Title	Proportion of Participants Whose Spironolactone Dose Was Increased.
Time Frame	28 Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patiromer	Placebo
Arm/Group Description	Spironolactone + Patiromer Participants received patiromer (15 g twice daily [BID]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was > 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was > 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or > 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.	Spironolactone + Placebo Participants received placebo (twice daily [BID]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was > 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was > 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or > 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.
Measure Participants	55	49
Number [percentage of participants]	90.9 165.3%	73.5 150%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Patiromer, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.022
	Comments
	Method	Fisher Exact
	Comments

5. Secondary Outcome

Title	Proportion of Participants With an Increase in Serum Potassium Level From Baseline to the End of the 28-day Treatment Period That Was ≥ 0.5 mEq/L
Time Frame	Baseline and Day 28

Outcome Measure Data

Analysis Population Description

Analysis was determined using LOCF.

Arm/Group Title	Patiromer	Placebo
Arm/Group Description	Spironolactone + Patiromer Participants received patiromer (15 g twice daily [BID]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was > 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was > 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or > 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.	Spironolactone + Placebo Participants received placebo (twice daily [BID]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was > 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was > 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or > 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.
Measure Participants	55	49
Number [percentage of participants]	12.7 23.1%	24.5 50%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Patiromer, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	= 0.136
	Comments
	Method	Fisher Exact
	Comments

6. Secondary Outcome

Title	Time to First Elevated Serum K+ > 5.5 mEq/L.
Time Frame	28 Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patiromer	Placebo
Arm/Group Description	Spironolactone + Patiromer Participants received patiromer (15 g twice daily [BID]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was > 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was > 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or > 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.	Spironolactone + Placebo Participants received placebo (twice daily [BID]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was > 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was > 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or > 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.
Measure Participants	55	49
Median (95% Confidence Interval) [days]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Patiromer, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	= 0.015
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Time Frame	Up to 7 days after Day 28 or last patiromer dose, whichever was earlier.
Adverse Event Reporting Description	Randomized participants who received at least one dose of trial medication.
Arm/Group Title	Patiromer		Placebo
Arm/Group Description	Spironolactone + Patiromer Participants received patiromer (15 g twice daily [BID]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was > 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was > 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or > 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.		Spironolactone + Placebo Participants received placebo (twice daily [BID]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was > 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was > 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or > 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.
All Cause Mortality
	Patiromer		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Patiromer		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/56 (3.6%)		2/49 (4.1%)
Cardiac disorders
Coronary artery disease	2/56 (3.6%)		0/49 (0%)
Acute myocardial infarction	1/56 (1.8%)		0/49 (0%)
Atrial fibrillation	1/56 (1.8%)		0/49 (0%)
General disorders
Sudden cardiac death	0/56 (0%)		1/49 (2%)
Metabolism and nutrition disorders
Gout	0/56 (0%)		1/49 (2%)
Other (Not Including Serious) Adverse Events
	Patiromer		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/56 (19.6%)		1/49 (2%)
Gastrointestinal disorders
Constipation	3/56 (5.4%)		0/49 (0%)
Diarrhoea	3/56 (5.4%)		1/49 (2%)
Flatulence	4/56 (7.1%)		0/49 (0%)
Investigations
Blood urea increased	3/56 (5.4%)		0/49 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Our agreements generally provide that PI cannot publish single site data before publication of the multi-site publication, unless 1 year has elapsed since completion of the study at all sites. Thereafter, PI may publish provided that PI shall: provide a copy of the publication to sponsor at least 60 days in advance of submission for publication; delete sponsor's confidential information as requested; and delay publication up to an additional 90 days to permit protection of intellectual property.