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

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ClinicalTrials.gov Identifier: NCT01130597
Recruitment Status : Completed
First Posted : May 26, 2010
Results First Posted : January 28, 2016
Last Update Posted : January 28, 2016
Sponsor:
Information provided by (Responsible Party):
Relypsa, Inc.

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Condition Heart Failure
Interventions Drug: patiromer
Drug: spironolactone
Enrollment 63
Recruitment Details  
Pre-assignment Details 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).
Arm/Group Title Patiromer
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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.

Period Title: Overall Study
Started 63
Completed 56
Not Completed 7
Reason Not Completed
Protocol-specified (High K+)             1
Adverse Event             4
Death             1
Protocol Violation             1
Arm/Group Title Patiromer
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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 Number of Baseline Participants 63
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[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 63 participants
<=18 years
0
   0.0%
Between 18 and 65 years
17
  27.0%
>=65 years
46
  73.0%
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 63 participants
70.8
(53 to 86)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 63 participants
Female
24
  38.1%
Male
39
  61.9%
1.Primary Outcome
Title Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at the End of Treatment
Hide Description [Not Specified]
Time Frame 56 days
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[Not Specified]
Arm/Group Title Patiromer
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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 Number of Participants Analyzed 63
Measure Type: Number
Unit of Measure: percentage of participants
90.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Patiromer
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage of Participants
Estimated Value 90.5
Confidence Interval (2-Sided) 95%
80.4 to 96.4
Estimation Comments Clopper-Pearson was used to arrive at the 95% Confidence Interval
2.Secondary Outcome
Title Percentage of Participants With Serum Potassium in the Range of 3.5 – 5.5 mEq/L at Week 4
Hide Description [Not Specified]
Time Frame 28 Days
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Participants with available data at Week 4.
Arm/Group Title Patiromer
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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 Number of Participants Analyzed 61
Measure Type: Number
Unit of Measure: percentage of participants
96.7
3.Secondary Outcome
Title Percentage of Participants With Serum Potassium in the Range of 3.5 – 5.5 mEq/L at Week 8
Hide Description [Not Specified]
Time Frame 56 Days
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Hide Analysis Population Description
Participants with available data at Week 8.
Arm/Group Title Patiromer
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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 Number of Participants Analyzed 57
Measure Type: Number
Unit of Measure: percentage of participants
93.0
4.Secondary Outcome
Title Percentage of Participants With Serum Potassium in the Range of 4.0 – 5.1 mEq/L at Week 4
Hide Description [Not Specified]
Time Frame 28 Days
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Hide Analysis Population Description
Participants with available data at Week 4.
Arm/Group Title Patiromer
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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 Number of Participants Analyzed 61
Measure Type: Number
Unit of Measure: percentage of participants
78.7
5.Secondary Outcome
Title Percentage of Participants With Serum Potassium in the Range of 4.0 – 5.1 mEq/L at Week 8
Hide Description [Not Specified]
Time Frame 56 Days
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Hide Analysis Population Description
Participants with available data at Week 8.
Arm/Group Title Patiromer
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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 Number of Participants Analyzed 57
Measure Type: Number
Unit of Measure: percentage of participants
86.0
6.Secondary Outcome
Title Percentage of Participants With Serum Potassium in the Range of 4.0 – 5.1 mEq/L at the End of Treatment
Hide Description [Not Specified]
Time Frame 56 Days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Patiromer
Hide Arm/Group Description:

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 Number of Participants Analyzed 63
Measure Type: Number
Unit of Measure: percentage of participants
84.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Patiromer
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage of Participants
Estimated Value 84.1
Confidence Interval (2-Sided) 95%
72.7 to 92.1
Estimation Comments Clopper-Pearson was used to arrive at the 95% Confidence Interval
7.Secondary Outcome
Title Mean Dose of Patiromer at End of Treatment
Hide Description [Not Specified]
Time Frame 56 Days
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Patiromer
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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 Number of Participants Analyzed 63
Mean (Standard Deviation)
Unit of Measure: grams
22.5  (7.8)
8.Secondary Outcome
Title Percentage of Participants Requiring Patiromer Uptitration
Hide Description [Not Specified]
Time Frame 56 Days
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[Not Specified]
Arm/Group Title Patiromer
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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 Number of Participants Analyzed 63
Measure Type: Number
Unit of Measure: percentage of participants
33.3
9.Secondary Outcome
Title Percentage of Participants Requiring Patiromer Downtitration
Hide Description [Not Specified]
Time Frame 56 Days
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Patiromer
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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 Number of Participants Analyzed 63
Measure Type: Number
Unit of Measure: percentage of participants
12.7
10.Secondary Outcome
Title Median Time to First Patiromer Dose Titration
Hide Description [Not Specified]
Time Frame 56 Days
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[Not Specified]
Arm/Group Title Patiromer
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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 Number of Participants Analyzed 63
Median (95% Confidence Interval)
Unit of Measure: days
21
(14.0 to 36.0)
11.Secondary Outcome
Title Mean Number of Patiromer Titrations
Hide Description [Not Specified]
Time Frame 56 Days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Patiromer
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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 Number of Participants Analyzed 63
Mean (Standard Deviation)
Unit of Measure: patiromer titrations
1.3  (1.1)
12.Secondary Outcome
Title Mean Patiromer Dose at Week 1
Hide Description [Not Specified]
Time Frame Up to Week 1
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Patiromer
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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 Number of Participants Analyzed 63
Mean (Standard Deviation)
Unit of Measure: grams
20.0  (0.0)
13.Secondary Outcome
Title Mean Patiromer Dose at Week 4
Hide Description [Not Specified]
Time Frame Up to Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Patiromer
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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 Number of Participants Analyzed 63
Mean (Standard Deviation)
Unit of Measure: grams
21.9  (8.5)
14.Secondary Outcome
Title Mean Patiromer Dose at Week 8
Hide Description [Not Specified]
Time Frame Up to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Patiromer
Hide Arm/Group Description:

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 Number of Participants Analyzed 63
Mean (Standard Deviation)
Unit of Measure: grams
23.0  (12.4)
15.Secondary Outcome
Title Mean Change From Baseline in Serum Potassium to End of Treatment
Hide Description [Not Specified]
Time Frame 56 Days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Patiromer
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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 Number of Participants Analyzed 63
Mean (Standard Deviation)
Unit of Measure: mEq/L
-0.13  (0.686)
16.Secondary Outcome
Title Percentage of Participants Discontinuing Due to Hyperkalemia (Serum Potassium > 5.5 mEq/L)
Hide Description [Not Specified]
Time Frame 56 Days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Patiromer
Hide Arm/Group Description:

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 Number of Participants Analyzed 63
Measure Type: Number
Unit of Measure: percentage of participants
1.6
17.Secondary Outcome
Title Percentage of Patients Whose Spironolactone Dose Was Increased Up to 50 mg/Day
Hide Description [Not Specified]
Time Frame 56 Days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Patiromer
Hide Arm/Group Description:

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 Number of Participants Analyzed 63
Measure Type: Number
Unit of Measure: percentage of participants
100
18.Secondary Outcome
Title Change in Urine Albumin to Creatinine Ratio (ACR) From Baseline to Week 4 Among Participants With ACR ≥ 30 mg/g at Baseline
Hide Description [Not Specified]
Time Frame Baseline and Day 28
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Hide Analysis Population Description
Participants with urine ACR ≥ 30 mg/g at baseline and available data at Week 4
Arm/Group Title Patiromer
Hide Arm/Group Description:

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 Number of Participants Analyzed 31
Mean (Standard Error)
Unit of Measure: mg/g
-291.01  (130.7973)
19.Secondary Outcome
Title Change in ACR From Baseline to Week 8 Among Participants With Urine ACR ≥ 30 mg/g at Baseline
Hide Description [Not Specified]
Time Frame Baseline and Day 56
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with urine ACR ≥ 30 mg/g at baseline and available data at Week 8
Arm/Group Title Patiromer
Hide Arm/Group Description:

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 Number of Participants Analyzed 30
Mean (Standard Error)
Unit of Measure: mg/g
-291.06  (141.5644)
Time Frame Up to 7 days after Day 56 or last patiromer dose, whichever was earlier.
Adverse Event Reporting Description Participants who received at least one dose of trial medication.
 
Arm/Group Title Patiromer
Hide Arm/Group Description

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.

All-Cause Mortality
Patiromer
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Patiromer
Affected / at Risk (%)
Total   6/63 (9.52%) 
Cardiac disorders   
Acute myocardial infarction  1  1/63 (1.59%) 
General disorders   
Sudden cardiac death  1  1/63 (1.59%) 
Sudden death  1 [1]  1/63 (1.59%) 
Infections and infestations   
Pneumonia  1  1/63 (1.59%) 
Staphylococcal sepsis  1  1/63 (1.59%) 
Subcutaneous abscess  1  1/63 (1.59%) 
Metabolism and nutrition disorders   
Diabetes mellitus  1  1/63 (1.59%) 
Renal and urinary disorders   
Azotaemia  1  1/63 (1.59%) 
Renal failure acute  1  3/63 (4.76%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.0
[1]
Sudden death occurred during the follow up period, after completing the study.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Patiromer
Affected / at Risk (%)
Total   4/63 (6.35%) 
Gastrointestinal disorders   
Abdominal discomfort  1  4/63 (6.35%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.0
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.
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.
Results Point of Contact
Name/Title: Medical Information
Organization: Relypsa, Inc.
Phone: 1-844-relypsa
Responsible Party: Relypsa, Inc.
ClinicalTrials.gov Identifier: NCT01130597     History of Changes
Other Study ID Numbers: RLY5016-204
First Submitted: May 24, 2010
First Posted: May 26, 2010
Results First Submitted: November 11, 2015
Results First Posted: January 28, 2016
Last Update Posted: January 28, 2016