Clinical trial NCT00868439: Evaluation of Patiromer in Heart Failure Patients
Official title: A Multicenter, Randomized, Double-blind, Placebo-Controlled, Parallel-Group, Multiple-Dose Study to Evaluate the Effects of Patiromer in Heart Failure Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hyperkalemia
Heart Failure
Keywords: HF
Heart failure
hyperkalemia
chronic kidney disease
prevention of hyperkalemia in heart failure participants
Lead sponsor: Vifor Pharma
Sponsor class: INDUSTRY
Collaborators: name: Medpace, Inc.
First posted: 2009-03-25
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study was to assess the effects of patiromer on serum potassium participants with heart failure. This study also assessed the safety and tolerability of patiromer in participants with heart failure.

Detailed description: This was a double-blind, randomized, placebo-controlled, parallel-group, multiple-dose study in congestive heart failure participants. Depending on the outcome from the initial cohort of 100 participants (Part 1), a second cohort of 170 participants could have been enrolled (Part 2). Based on the results of Part 1 of the study, Part 2 was not conducted.

Participants were randomly assigned to and received patiromer (30 g/day) or placebo for up to 28 days. All participants also received spironolactone; the initial spironolactone dose was 25 mg daily and was increased to 50 mg daily for participants who had a serum potassium ≤ 5.1 mEq/L on treatment Day 14. Study visits occurred on treatment Days 3, 7, 14, 17, 21 and 28. A safety follow-up contact was made 7 days after administration of last dose of study drug.

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

Primary outcomes:
measure: Change From Baseline in Serum Potassium to the End of the 28-day Treatment Period.
timeFrame: Baseline and Day 28
Secondary outcomes:
measure: Proportion of Participants With a Serum Potassium Level During the 28-day Treatment Period That Was > 5.5 mEq/L.
timeFrame: 28 Days
measure: Proportion of Participants Discontinuing the Study Due to Serum Potassium Elevation (Serum K+ > 5.5 mEq/L).
timeFrame: 28 Days
measure: Proportion of Participants Whose Spironolactone Dose Was Increased.
timeFrame: 28 Days
measure: 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
timeFrame: Baseline and Day 28
measure: Time to First Elevated Serum K+ > 5.5 mEq/L.
timeFrame: 28 Days
Other outcomes:
Locations:
city: Miami
country: United States
facility: Investigator Site 029
state: Florida
city: Port Charlotte
country: United States
facility: Investigator Site 031
state: Florida
city: Peoria
country: United States
facility: Investigator Site 009
state: Illinois
city: Minneapolis
country: United States
facility: Investigator Site 018
state: Minnesota
city: Buffalo
country: United States
facility: Investigator Site 020
state: New York
city: Northport
country: United States
facility: Investigator Site 005
state: New York
city: Columbus
country: United States
facility: Investigator Site 022
state: Ohio
city: Dallas
country: United States
facility: Investigator Site 001
state: Texas
city: Salt Lake City
country: United States
facility: Investigator Site 019
state: Utah
city: Brno
country: Czechia
facility: Investigator Site 102
city: Prague
country: Czechia
facility: Investigator Site 104
city: Prague
country: Czechia
facility: Investigator Site 103
city: Tbilisi
country: Georgia
facility: Investigator Site 605
city: Tbilisi
country: Georgia
facility: Investigator Site 602
city: Tbilisi
country: Georgia
facility: Investigator Site 604
city: Tbilisi
country: Georgia
facility: Investigator Site 603
city: Gottingen
country: Germany
facility: Investigator Site 201
city: Heidelberg
country: Germany
facility: Investigator Site 202
city: Warsaw
country: Poland
facility: Investigator Site 305
city: Barnaul
country: Russian Federation
facility: Investigator Site 409
city: Kemerovo
country: Russian Federation
facility: Investigator Site 407
city: Moscow
country: Russian Federation
facility: Investigator Site 406
city: Moscow
country: Russian Federation
facility: Investigator Site 402
city: Moscow
country: Russian Federation
facility: Investigator Site 403
city: St Petersburg
country: Russian Federation
facility: Investigator Site 404
city: St Petersburg
country: Russian Federation
facility: Investigator Site 412
city: St Petersburg
country: Russian Federation
facility: Investigator Site 405
city: Dnipropetrovsk
country: Ukraine
facility: Investigator Site 507
city: Kharkiv
country: Ukraine
facility: Investigator Site 502
city: Kharkiv
country: Ukraine
facility: Investigator Site 509
city: Kiev
country: Ukraine
facility: Investigator Site 504
city: Kiev
country: Ukraine
facility: Investigator Site 506
city: Kiev
country: Ukraine
facility: Investigator Site 501
Study officials:
affiliation: Relypsa, Inc.
name: Director Clinical Operations
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Natale P, Palmer SC, Ruospo M, Saglimbene VM, Strippoli GF. Potassium binders for chronic hyperkalaemia in people with chronic kidney disease. Cochrane Database Syst Rev. 2020 Jun 26;6(6):CD013165. doi: 10.1002/14651858.CD013165.pub2.