Trial Outcomes & Findings for Evaluation of Patiromer Titration in Heart Failure Patients With Chronic Kidney Disease (NCT NCT01130597)

NCT ID: NCT01130597

Last Updated: 2021-05-12

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 63 participants
• Primary outcome timeframe: 56 days
• Results posted on: 2021-05-12

Participant Flow

Eligible participants were ≥ 18 years old, had a history of chronic HF, were clinically indicated to initiate spironolactone therapy, had a serum potassium measurement of 4.3 - 5.1 mEq/L at screening and baseline, had CKD (eGFR < 60 mL/min/1.73 m2 at screening), and were taking one or more HF therapies (ACEIs, ARBs, or BBs).

Participant milestones

Measure	Patiromer Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed.
Overall Study STARTED	63
Overall Study COMPLETED	56
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Measure	Patiromer Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed.
Overall Study Protocol-specified (High K+)	1
Overall Study Adverse Event	4
Overall Study Death	1
Overall Study Protocol Violation	1

Baseline Characteristics

Evaluation of Patiromer Titration in Heart Failure Patients With Chronic Kidney Disease

Baseline characteristics by cohort

Measure	Patiromer n=63 Participants Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	17 Participants n=5 Participants
Age, Categorical >=65 years	46 Participants n=5 Participants
Age, Continuous	70.8 years n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants
Sex: Female, Male Male	39 Participants n=5 Participants

PRIMARY outcome

Timeframe: 56 days

Outcome measures

Measure

Patiromer n=63 Participants Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed.

Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at the End of Treatment

90.5 percentage of participants

SECONDARY outcome

Timeframe: 28 Days

Population: Participants with available data at Week 4.

Outcome measures

Measure

Patiromer n=61 Participants Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed.

Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at Week 4

96.7 percentage of participants

SECONDARY outcome

Timeframe: 56 Days

Population: Participants with available data at Week 8.

Outcome measures

Measure

Patiromer n=57 Participants Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed.

Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at Week 8

93.0 percentage of participants

SECONDARY outcome

Timeframe: 28 Days

Population: Participants with available data at Week 4.

Outcome measures

Measure

Patiromer n=61 Participants Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed.

Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at Week 4

78.7 percentage of participants

SECONDARY outcome

Timeframe: 56 Days

Population: Participants with available data at Week 8.

Outcome measures

Measure

Patiromer n=57 Participants Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed.

Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at Week 8

86.0 percentage of participants

SECONDARY outcome

Timeframe: 56 Days

Outcome measures

Measure

Patiromer n=63 Participants Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed.

Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at the End of Treatment

84.1 percentage of participants

SECONDARY outcome

Timeframe: 56 Days

Outcome measures

Measure

Patiromer n=63 Participants Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed.

Mean Dose of Patiromer at End of Treatment

22.5 grams Standard Deviation 7.8

SECONDARY outcome

Timeframe: 56 Days

Outcome measures

Measure

Patiromer n=63 Participants Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed.

Percentage of Participants Requiring Patiromer Uptitration

33.3 percentage of participants

SECONDARY outcome

Timeframe: 56 Days

Outcome measures

Measure

Patiromer n=63 Participants Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed.

Percentage of Participants Requiring Patiromer Downtitration

12.7 percentage of participants

SECONDARY outcome

Timeframe: 56 Days

Outcome measures

Measure

Patiromer n=63 Participants Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed.

Median Time to First Patiromer Dose Titration

21 days Interval 14.0 to 36.0

SECONDARY outcome

Timeframe: 56 Days

Outcome measures

Measure

Patiromer n=63 Participants Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed.

Mean Number of Patiromer Titrations

1.3 patiromer titrations Standard Deviation 1.1

SECONDARY outcome

Timeframe: Up to Week 1

Outcome measures

Measure

Patiromer n=63 Participants Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed.

Mean Patiromer Dose at Week 1

20.0 grams Standard Deviation 0.0

SECONDARY outcome

Timeframe: Up to Week 4

Outcome measures

Measure

Patiromer n=63 Participants Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed.

Mean Patiromer Dose at Week 4

21.9 grams Standard Deviation 8.5

SECONDARY outcome

Timeframe: Up to Week 8

Outcome measures

Measure

Patiromer n=63 Participants Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed.

Mean Patiromer Dose at Week 8

23.0 grams Standard Deviation 12.4

SECONDARY outcome

Timeframe: 56 Days

Outcome measures

Measure

Patiromer n=63 Participants Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed.

Mean Change From Baseline in Serum Potassium to End of Treatment

-0.13 mEq/L Standard Deviation 0.686

SECONDARY outcome

Timeframe: 56 Days

Outcome measures

Measure

Patiromer n=63 Participants Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed.

Percentage of Participants Discontinuing Due to Hyperkalemia (Serum Potassium > 5.5 mEq/L)

1.6 percentage of participants

SECONDARY outcome

Timeframe: 56 Days

Outcome measures

Measure

Patiromer n=63 Participants Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed.

Percentage of Patients Whose Spironolactone Dose Was Increased Up to 50 mg/Day

100 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Day 28

Population: Participants with urine ACR ≥ 30 mg/g at baseline and available data at Week 4

Outcome measures

Measure

Patiromer n=31 Participants Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed.

Change in Urine Albumin to Creatinine Ratio (ACR) From Baseline to Week 4 Among Participants With ACR ≥ 30 mg/g at Baseline

-291.01 mg/g Standard Error 130.7973

SECONDARY outcome

Timeframe: Baseline and Day 56

Population: Participants with urine ACR ≥ 30 mg/g at baseline and available data at Week 8

Outcome measures

Measure

Patiromer n=30 Participants Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed.

Change in ACR From Baseline to Week 8 Among Participants With Urine ACR ≥ 30 mg/g at Baseline

-291.06 mg/g Standard Error 141.5644

Adverse Events

Patiromer

Serious events: 6 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Patiromer n=63 participants at risk Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed.
Cardiac disorders Acute myocardial infarction	1.6% 1/63 • Up to 7 days after Day 56 or last patiromer dose, whichever was earlier. Participants who received at least one dose of trial medication.
General disorders Sudden cardiac death	1.6% 1/63 • Up to 7 days after Day 56 or last patiromer dose, whichever was earlier. Participants who received at least one dose of trial medication.
General disorders Sudden death	1.6% 1/63 • Up to 7 days after Day 56 or last patiromer dose, whichever was earlier. Participants who received at least one dose of trial medication.
Infections and infestations Pneumonia	1.6% 1/63 • Up to 7 days after Day 56 or last patiromer dose, whichever was earlier. Participants who received at least one dose of trial medication.
Infections and infestations Staphylococcal sepsis	1.6% 1/63 • Up to 7 days after Day 56 or last patiromer dose, whichever was earlier. Participants who received at least one dose of trial medication.
Infections and infestations Subcutaneous abscess	1.6% 1/63 • Up to 7 days after Day 56 or last patiromer dose, whichever was earlier. Participants who received at least one dose of trial medication.
Metabolism and nutrition disorders Diabetes mellitus	1.6% 1/63 • Up to 7 days after Day 56 or last patiromer dose, whichever was earlier. Participants who received at least one dose of trial medication.
Renal and urinary disorders Azotaemia	1.6% 1/63 • Up to 7 days after Day 56 or last patiromer dose, whichever was earlier. Participants who received at least one dose of trial medication.
Renal and urinary disorders Renal failure acute	4.8% 3/63 • Up to 7 days after Day 56 or last patiromer dose, whichever was earlier. Participants who received at least one dose of trial medication.

Other adverse events

Measure

Patiromer n=63 participants at risk Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed.

Gastrointestinal disorders Abdominal discomfort

6.3% 4/63 • Up to 7 days after Day 56 or last patiromer dose, whichever was earlier. Participants who received at least one dose of trial medication.

Additional Information

Medical Information

Relypsa, Inc.

Phone: 1-844-relypsa

Email: medinfo@relypsa.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER