Evaluation of Patiromer in Heart Failure Patients (PEARL-HF)

This study has been completed.
Sponsor:
Collaborator:
Medpace, Inc.
Information provided by (Responsible Party):
Relypsa, Inc.
ClinicalTrials.gov Identifier:
NCT00868439
First received: March 23, 2009
Last updated: January 25, 2016
Last verified: January 2016
Results First Received: November 11, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Conditions: Hyperkalemia
Heart Failure
Interventions: Drug: patiromer
Drug: placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
120 subjects were randomized in Part 1 of the study (60 to each treatment group). Of these, 120 randomized subjects, 105 received either RLY5016 Powder for Suspension (n = 56) or placebo (n = 49).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Eligible participants ≥ 18 y/o, had history of chronic HF, clinically initiated spironolactone therapy, serum K+ = 4.3 – 5.1 mEq/L at screening and baseline, and either had 1) CKD, w/ eGFR < 60 mL/min and receiving HF therapies or 2) documented history of hyperkalemia led to discontinuation w/ aldosterone antagonist w/in 6 months prior to baseline.

Reporting Groups
  Description
Patiromer

Spironolactone + Patiromer

Participants received patiromer (15 g twice daily [BID]).

Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was > 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was > 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant’s serum potassium level was confirmed to be ≤ 3.5 mEq/L or > 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.

Placebo

Spironolactone + Placebo

Participants received placebo (twice daily [BID]).

Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was > 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was > 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant’s serum potassium level was confirmed to be ≤ 3.5 mEq/L or > 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.


Participant Flow:   Overall Study
    Patiromer     Placebo  
STARTED     56     49  
COMPLETED     48     40  
NOT COMPLETED     8     9  
Adverse Event                 4                 3  
Prot-Specified W/D Criteria (Serum K+)                 2                 3  
Death                 0                 1  
Protocol Violation                 1                 1  
Physician Decision                 1                 0  
Withdrawal by Subject                 0                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
One participant received one dose of patiromer and did not return to the clinic in a timely manner; the participant was terminated from the study for protocol noncompliance, and because the participant did not have post-treatment efficacy data, the participant was excluded from the Full Analysis Set but retained in the Safety Analysis Set.

Reporting Groups
  Description
Patiromer

Spironolactone + Patiromer

Participants received patiromer (15 g twice daily [BID]).

Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was > 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was > 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant’s serum potassium level was confirmed to be ≤ 3.5 mEq/L or > 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.

Placebo

Spironolactone + Placebo

Participants received placebo (twice daily [BID]).

Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant’s serum potassium (based on local laboratory determination) was > 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was > 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant’s serum potassium level was confirmed to be ≤ 3.5 mEq/L or > 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.

Total Total of all reporting groups

Baseline Measures
    Patiromer     Placebo     Total  
Number of Participants  
[units: participants]
  55     49     104  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     16     14     30  
>=65 years     39     35     74  
Age  
[units: years]
Mean (Standard Deviation)
  68.3  (8.66)     68.2  (10.46)     68.3  (9.50)  
Gender  
[units: participants]
     
Female     26     15     41  
Male     29     34     63  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in Serum Potassium to the End of the 28-day Treatment Period.   [ Time Frame: Baseline and Day 28 ]

2.  Secondary:   Proportion of Participants With a Serum Potassium Level During the 28-day Treatment Period That Was > 5.5 mEq/L.   [ Time Frame: 28 Days ]

3.  Secondary:   Proportion of Participants Discontinuing the Study Due to Serum Potassium Elevation (Serum K+ > 5.5 mEq/L).   [ Time Frame: 28 Days ]

4.  Secondary:   Proportion of Participants Whose Spironolactone Dose Was Increased.   [ Time Frame: 28 Days ]

5.  Secondary:   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   [ Time Frame: Baseline and Day 28 ]

6.  Secondary:   Time to First Elevated Serum K+ > 5.5 mEq/L.   [ Time Frame: 28 Days ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Medical Information
Organization: Relypsa, Inc.
phone: 1-844-relypsa
e-mail: medinfo@relypsa.com


Publications of Results:

Responsible Party: Relypsa, Inc.
ClinicalTrials.gov Identifier: NCT00868439     History of Changes
Other Study ID Numbers: RLY5016-202
Study First Received: March 23, 2009
Results First Received: November 11, 2015
Last Updated: January 25, 2016
Health Authority: United States: Food and Drug Administration
Czech Republic: State Institute for Drug Control
Germany: Federal Institute for Drugs and Medical Devices
Poland: Ministry of Health
Georgia: Ministry of Health
Russia: Ministry of Health of the Russian Federation
United States: Institutional Review Board
Czech Republic: Ethics Committee
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Poland: Ethics Committee
Russia: Ethics Committee
Ukraine: Ethics Committee
Ukraine: State Pharmacological Center - Ministry of Health