Evaluation of Patiromer in Heart Failure Patients | NCT00868439

Status Module

Name	Class
Medpace, Inc.	INDUSTRY

Description Module

Label	Type	Description	Intervention Names
patiromer	Active Comparator		Drug: patiromer
placebo	Placebo Comparator		Drug: placebo

Name	Type	Description	Arm Group Labels	Other Names
patiromer	Drug	Active investigational drug	patiromer	RLY5016

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

Measure	Description	Time Frame
Proportion of Participants With a Serum Potassium Level During the 28-day Treatment Period That Was > 5.5 mEq/L.	Analysis based on central laboratory data.	28 Days
Proportion of Participants Discontinuing the Study Due to Serum Potassium Elevation (Serum K+ > 5.5 mEq/L).

Eligibility Module

Eligibility Criteria

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

Name	Affiliation	Role
Director Clinical Operations	Relypsa, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Investigator Site 029		Miami	Florida	33176	United States
Investigator Site 031

PubMed Identifier	Type	Citation	Retractions
21208974	Result	Pitt B, Anker SD, Bushinsky DA, Kitzman DW, Zannad F, Huang IZ; PEARL-HF Investigators. Evaluation of the efficacy and safety of RLY5016, a polymeric potassium binder, in a double-blind, placebo-controlled study in patients with chronic heart failure (the PEARL-HF) trial. Eur Heart J. 2011 Apr;32(7):820-8. doi: 10.1093/eurheartj/ehq502. Epub 2011 Jan 5.
32588430

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Patiromer	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Patiromer	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.
BG001	Placebo	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.
BG002	Total	Total of all reporting groups

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

Change From Baseline in Serum Potassium to the End of the 28-day Treatment Period.

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

Posted

Least Squares Mean

Standard Error

mEq/L

Baseline and Day 28

ID	Title	Description
OG000	Patiromer	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.
OG001	Placebo	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.

Units	Counts
Participants	OG00055 OG00149

Title

Denominators

Categories

Title	Measurements
	OG000-0.21± 0.066 OG0010.23± 0.072

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		ANCOVA		< 0.001						2-Sided								Superiority or Other (legacy)

Secondary

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

Analysis based on central laboratory data.

Posted

Number

percentage of participants

28 Days

ID	Title	Description
OG000	Patiromer	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.
OG001	Placebo	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.

Secondary

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

Analysis based on local laboratory data.

Posted

Number

percentage of participants

28 Days

ID	Title	Description
OG000	Patiromer	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.
OG001	Placebo	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.

Secondary

Proportion of Participants Whose Spironolactone Dose Was Increased.

Posted

Number

percentage of participants

28 Days

ID	Title	Description
OG000	Patiromer	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.
OG001	Placebo	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.

Secondary

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

Analysis was determined using LOCF.

Posted

Number

percentage of participants

Baseline and Day 28

ID	Title	Description
OG000	Patiromer	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.
OG001	Placebo	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.

Secondary

Time to First Elevated Serum K+ > 5.5 mEq/L.

Posted

Median

95% Confidence Interval

days

28 Days

ID	Title	Description
OG000	Patiromer	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.
OG001	Placebo	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.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Patiromer	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.			2	56	11	56
EG001	Placebo	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.			2	49	1	49

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Coronary artery disease	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0002 affected56 at risk EG0010 affected49 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected56 at risk EG0010 affected49 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected56 at risk EG0010 affected49 at risk
Sudden cardiac death	General disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected56 at risk EG0011 affected49 at risk
Gout	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected56 at risk EG0011 affected49 at risk

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0003 affected56 at risk EG0010 affected49 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0003 affected56 at risk EG0011 affected49 at risk
Flatulence	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0004 affected56 at risk EG0010 affected49 at risk
Blood urea increased	Investigations	MedDRA (12.0)	Systematic Assessment	EG0003 affected56 at risk EG0010 affected49 at risk

ID	Term
D006947	Hyperkalemia
D006333	Heart Failure
D051436	Renal Insufficiency, Chronic

ID	Term
D014883	Water-Electrolyte Imbalance
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D006331	Heart Diseases
D002318	Cardiovascular Diseases
D051437	Renal Insufficiency
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms