Clinical trial NCT01130597: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure
Keywords: HF
Heart failure
hyperkalemia
chronic kidney disease
prevention of hyperkalemia in heart failure participants
Lead sponsor: Vifor Pharma
Sponsor class: INDUSTRY
First posted: 2010-05-26
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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 5.5 mEq/L on two consecutive scheduled study visits, despite titration of patiromer or spironolactone, were withdrawn from the study, permanently discontinued patiromer and spironolactone, and returned for a follow-up visit within 7 days.

Eligibility criteria: Inclusion Criteria:

1. Chronic HF clinically indicated to receive spironolactone therapy
2. Age 18 years or older
3. Local laboratory serum potassium values of 4.3 - 5.1 mEq/L at screening and baseline
4. CKD (estimated glomerular filtration rate \[eGFR\] \< 60 mL/min/1.73m2 at screening based on central lab creatinine measurement)
5. On at least one of the following HF therapies: ACEI, ARB, or BB
6. 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
7. 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
8. Provide their written informed consent prior to participation in the study

Exclusion Criteria:

1. History of bowel obstruction, swallowing disorders, severe gastrointestinal disorders or major gastrointestinal surgery
2. Uncorrected primary severe valvular disease, known obstructive or restrictive cardiomyopathy, uncontrolled or hemodynamically unstable arrhythmia
3. 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
4. Heart transplant recipient, or anticipated need for transplant during study participation
5. 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
6. Current dialysis participant, or anticipated need for dialysis during study participation
7. Prior kidney transplant, or anticipated need for transplant during study participation
8. Metastatic, late-stage or end-stage cancer with \< 12 months life expectancy or at risk for tumor lysis syndrome
9. History of alcoholism or drug/chemical abuse within 1 year
10. Sustained systolic blood pressure \> 180 or \< 90 mmHg
11. Liver enzymes \[alanine aminotransferase (ALT), aspartate aminotransferase (AST)\] \> 3 times upper limit of normal
12. 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
13. Use of any intravenous cardiac medications within 21 days prior to baseline, or their anticipated need during study participation
14. 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
15. Use of potassium sparing medication including aldosterone antagonists or potassium supplements in the last 21 days prior to baseline
16. Use of any investigational medication within 30 days or 5 half-lives, whichever is longer, prior to baseline
17. Participants who have taken investigational product in this study, or a previous patiromer study
18. Inability to consume the study medication, or, in the opinion of the Investigator, inability to comply with the protocol
19. 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

Primary outcomes:
measure: Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at the End of Treatment
timeFrame: 56 days
Secondary outcomes:
measure: Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at Week 4
timeFrame: 28 Days
measure: Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at Week 8
timeFrame: 56 Days
measure: Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at Week 4
timeFrame: 28 Days
measure: Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at Week 8
timeFrame: 56 Days
measure: Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at the End of Treatment
timeFrame: 56 Days
measure: Mean Dose of Patiromer at End of Treatment
timeFrame: 56 Days
measure: Percentage of Participants Requiring Patiromer Uptitration
timeFrame: 56 Days
measure: Percentage of Participants Requiring Patiromer Downtitration
timeFrame: 56 Days
measure: Median Time to First Patiromer Dose Titration
timeFrame: 56 Days
measure: Mean Number of Patiromer Titrations
timeFrame: 56 Days
measure: Mean Patiromer Dose at Week 1
timeFrame: Up to Week 1
measure: Mean Patiromer Dose at Week 4
timeFrame: Up to Week 4
measure: Mean Patiromer Dose at Week 8
timeFrame: Up to Week 8
measure: Mean Change From Baseline in Serum Potassium to End of Treatment
timeFrame: 56 Days
measure: Percentage of Participants Discontinuing Due to Hyperkalemia (Serum Potassium > 5.5 mEq/L)
timeFrame: 56 Days
measure: Percentage of Patients Whose Spironolactone Dose Was Increased Up to 50 mg/Day
timeFrame: 56 Days
measure: Change in Urine Albumin to Creatinine Ratio (ACR) From Baseline to Week 4 Among Participants With ACR ≥ 30 mg/g at Baseline
timeFrame: Baseline and Day 28
measure: Change in ACR From Baseline to Week 8 Among Participants With Urine ACR ≥ 30 mg/g at Baseline
timeFrame: Baseline and Day 56
Other outcomes:
Locations:
city: Tbilisi
country: Georgia
facility: Investigator Site 11
city: Tbilisi
country: Georgia
facility: Investigator Site 12
city: Tbilisi
country: Georgia
facility: Investigator Site 13
city: Tbilisi
country: Georgia
facility: Investigator Site 14
city: Tbilisi
country: Georgia
facility: Investigator Site 15
city: Tbilisi
country: Georgia
facility: Investigator Site 16
city: Tbilisi
country: Georgia
facility: Investigator Site 17
city: Tbilisi
country: Georgia
facility: Investigator Site 18
city: Golnik
country: Slovenia
facility: Investigator Site 25
city: Izola
country: Slovenia
facility: Investigator Site 27
city: Ljubljana
country: Slovenia
facility: Investigator Site 21
city: Maribor
country: Slovenia
facility: Investigator Site 22
city: Slovenj Gradec
country: Slovenia
facility: Investigator Site 26
Study officials:
affiliation: Relypsa, Inc.
name: Director Clinical Operations
role: STUDY_DIRECTOR
References:
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.