Evaluation of Patiromer Titration in Heart Failure Patients With Chronic Kidney Disease
Primary Purpose
Heart Failure
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
patiromer
spironolactone
Sponsored by
About this trial
This is an interventional prevention trial for Heart Failure focused on measuring HF, Heart failure, hyperkalemia, chronic kidney disease, prevention of hyperkalemia in heart failure participants
Eligibility Criteria
Inclusion Criteria:
- Chronic HF clinically indicated to receive spironolactone therapy
- Age 18 years or older
- Local laboratory serum potassium values of 4.3 - 5.1 mEq/L at screening and baseline
- CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73m2 at screening based on central lab creatinine measurement)
- On at least one of the following HF therapies: ACEI, ARB, or BB
- 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
- Provide their written informed consent prior to participation in the study
Exclusion Criteria:
- History of bowel obstruction, swallowing disorders, severe gastrointestinal disorders or major gastrointestinal surgery
- Uncorrected primary severe 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 2 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 or at risk for tumor lysis syndrome
- History of alcoholism or drug/chemical abuse within 1 year
- Sustained systolic blood pressure > 180 or < 90 mmHg
- Liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST)] > 3 times upper limit of normal
- Loop and thiazide diuretics that have not been stable for at least 21 days prior to baseline or not anticipated to remain stable during study participation
- Use of any intravenous cardiac medications within 21 days prior to baseline, or their anticipated need during study participation
- Current use of polymer-based drugs (e.g., sevelamer, sodium polystyrene sulfonate, colesevelam, colestipol), phosphate binders (e.g., lanthanum carbonate), or other potassium binders, or their anticipated need during study participation
- Use of potassium sparing medication including aldosterone antagonists or potassium supplements in the last 21 days prior to baseline
- Use of any investigational medication within 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
Sites / Locations
- Investigator Site 11
- Investigator Site 12
- Investigator Site 13
- Investigator Site 14
- Investigator Site 15
- Investigator Site 16
- Investigator Site 17
- Investigator Site 18
- Investigator Site 25
- Investigator Site 27
- Investigator Site 21
- Investigator Site 22
- Investigator Site 26
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
patiromer
Arm Description
spironolactone + patiromer
Outcomes
Primary Outcome Measures
Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at the End of Treatment
Secondary Outcome Measures
Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at Week 4
Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at Week 8
Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at Week 4
Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at Week 8
Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at the End of Treatment
Mean Dose of Patiromer at End of Treatment
Percentage of Participants Requiring Patiromer Uptitration
Percentage of Participants Requiring Patiromer Downtitration
Median Time to First Patiromer Dose Titration
Mean Number of Patiromer Titrations
Mean Patiromer Dose at Week 1
Mean Patiromer Dose at Week 4
Mean Patiromer Dose at Week 8
Mean Change From Baseline in Serum Potassium to End of Treatment
Percentage of Participants Discontinuing Due to Hyperkalemia (Serum Potassium > 5.5 mEq/L)
Percentage of Patients Whose Spironolactone Dose Was Increased Up to 50 mg/Day
Change in Urine Albumin to Creatinine Ratio (ACR) From Baseline to Week 4 Among Participants With ACR ≥ 30 mg/g at Baseline
Change in ACR From Baseline to Week 8 Among Participants With Urine ACR ≥ 30 mg/g at Baseline
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01130597
Brief Title
Evaluation of Patiromer Titration in Heart Failure Patients With Chronic Kidney Disease
Official Title
A Multicenter, Open-Label, Single-Arm Study to Evaluate a Titration Regimen for Patiromer in Heart Failure Patients With Chronic Kidney Disease
Study Type
Interventional
2. Study Status
Record Verification Date
December 2015
Overall Recruitment Status
Completed
Study Start Date
May 2010 (undefined)
Primary Completion Date
September 2010 (Actual)
Study Completion Date
September 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Relypsa, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study was to evaluate the feasibility of individualized titration of patiromer according to serum potassium. This study also assessed the safety and tolerability of patiromer and the effects of patiromer on serum potassium in heart failure (HF) participants with chronic kidney disease (CKD).
Detailed Description
This was an open-label, single-arm study to evaluate a titration regimen for patiromer in approximately 63 HF participants with CKD receiving one or more of the following: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), or beta blockers (BBs). This study was considered to be exploratory.
Upon successful completion of screening evaluations (-10 to -5 days prior to enrollment), all eligible participants were assigned at Baseline (Day 0 visit) to an initial dose of patiromer (20 g/day) and spironolactone (25 mg/day).
Study visits for enrolled participants were scheduled for Days 3, 7, 14, 21, 28, 35, 42, 49 and 56. A follow-up visit occurred on Day 63.
At selected study visits, patiromer or spironolactone doses may have been titrated. The study dosing algorithm was designed to maintain an individual's serum potassium value in the range of 4.0 - 5.1 mEq/L (based on local lab data).
Any participant with a local laboratory serum potassium value < 3.5 or > 5.5 mEq/L on two consecutive scheduled study visits, despite titration of patiromer or spironolactone, were withdrawn from the study, permanently discontinued patiromer and spironolactone, and returned for a follow-up visit within 7 days.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
Keywords
HF, Heart failure, hyperkalemia, chronic kidney disease, prevention of hyperkalemia in heart failure participants
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
63 (Actual)
8. Arms, Groups, and Interventions
Arm Title
patiromer
Arm Type
Experimental
Arm Description
spironolactone + patiromer
Intervention Type
Drug
Intervention Name(s)
patiromer
Other Intervention Name(s)
RLY5016, Veltassa
Intervention Description
Active investigational drug
Intervention Type
Drug
Intervention Name(s)
spironolactone
Primary Outcome Measure Information:
Title
Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at the End of Treatment
Time Frame
56 days
Secondary Outcome Measure Information:
Title
Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at Week 4
Time Frame
28 Days
Title
Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at Week 8
Time Frame
56 Days
Title
Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at Week 4
Time Frame
28 Days
Title
Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at Week 8
Time Frame
56 Days
Title
Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at the End of Treatment
Time Frame
56 Days
Title
Mean Dose of Patiromer at End of Treatment
Time Frame
56 Days
Title
Percentage of Participants Requiring Patiromer Uptitration
Time Frame
56 Days
Title
Percentage of Participants Requiring Patiromer Downtitration
Time Frame
56 Days
Title
Median Time to First Patiromer Dose Titration
Time Frame
56 Days
Title
Mean Number of Patiromer Titrations
Time Frame
56 Days
Title
Mean Patiromer Dose at Week 1
Time Frame
Up to Week 1
Title
Mean Patiromer Dose at Week 4
Time Frame
Up to Week 4
Title
Mean Patiromer Dose at Week 8
Time Frame
Up to Week 8
Title
Mean Change From Baseline in Serum Potassium to End of Treatment
Time Frame
56 Days
Title
Percentage of Participants Discontinuing Due to Hyperkalemia (Serum Potassium > 5.5 mEq/L)
Time Frame
56 Days
Title
Percentage of Patients Whose Spironolactone Dose Was Increased Up to 50 mg/Day
Time Frame
56 Days
Title
Change in Urine Albumin to Creatinine Ratio (ACR) From Baseline to Week 4 Among Participants With ACR ≥ 30 mg/g at Baseline
Time Frame
Baseline and Day 28
Title
Change in ACR From Baseline to Week 8 Among Participants With Urine ACR ≥ 30 mg/g at Baseline
Time Frame
Baseline and Day 56
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Chronic HF clinically indicated to receive spironolactone therapy
Age 18 years or older
Local laboratory serum potassium values of 4.3 - 5.1 mEq/L at screening and baseline
CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73m2 at screening based on central lab creatinine measurement)
On at least one of the following HF therapies: ACEI, ARB, or BB
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
Provide their written informed consent prior to participation in the study
Exclusion Criteria:
History of bowel obstruction, swallowing disorders, severe gastrointestinal disorders or major gastrointestinal surgery
Uncorrected primary severe 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 2 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 or at risk for tumor lysis syndrome
History of alcoholism or drug/chemical abuse within 1 year
Sustained systolic blood pressure > 180 or < 90 mmHg
Liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST)] > 3 times upper limit of normal
Loop and thiazide diuretics that have not been stable for at least 21 days prior to baseline or not anticipated to remain stable during study participation
Use of any intravenous cardiac medications within 21 days prior to baseline, or their anticipated need during study participation
Current use of polymer-based drugs (e.g., sevelamer, sodium polystyrene sulfonate, colesevelam, colestipol), phosphate binders (e.g., lanthanum carbonate), or other potassium binders, or their anticipated need during study participation
Use of potassium sparing medication including aldosterone antagonists or potassium supplements in the last 21 days prior to baseline
Use of any investigational medication within 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Director Clinical Operations
Organizational Affiliation
Relypsa, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Investigator Site 11
City
Tbilisi
Country
Georgia
Facility Name
Investigator Site 12
City
Tbilisi
Country
Georgia
Facility Name
Investigator Site 13
City
Tbilisi
Country
Georgia
Facility Name
Investigator Site 14
City
Tbilisi
Country
Georgia
Facility Name
Investigator Site 15
City
Tbilisi
Country
Georgia
Facility Name
Investigator Site 16
City
Tbilisi
Country
Georgia
Facility Name
Investigator Site 17
City
Tbilisi
Country
Georgia
Facility Name
Investigator Site 18
City
Tbilisi
Country
Georgia
Facility Name
Investigator Site 25
City
Golnik
Country
Slovenia
Facility Name
Investigator Site 27
City
Izola
Country
Slovenia
Facility Name
Investigator Site 21
City
Ljubljana
Country
Slovenia
Facility Name
Investigator Site 22
City
Maribor
Country
Slovenia
Facility Name
Investigator Site 26
City
Slovenj Gradec
Country
Slovenia
12. IPD Sharing Statement
Citations:
PubMed Identifier
29369537
Citation
Pitt B, Bushinsky DA, Kitzman DW, Ruschitzka F, Metra M, Filippatos G, Rossignol P, Du Mond C, Garza D, Berman L, Lainscak M; Patiromer-204 Investigators. Evaluation of an individualized dose titration regimen of patiromer to prevent hyperkalaemia in patients with heart failure and chronic kidney disease. ESC Heart Fail. 2018 Jun;5(3):257-266. doi: 10.1002/ehf2.12265. Epub 2018 Jan 25.
Results Reference
derived
Links:
URL
http://www.relypsa.com
Description
Related Info
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Evaluation of Patiromer Titration in Heart Failure Patients With Chronic Kidney Disease
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