A placebo controlled Study of Patiromer for the Management of high potassium serum levels in Subjects Receiving a certain group of medications called Renin-Angiotensin-Aldosterone System Inhibitor for treatment of Heart failure.
- Conditions
- Management of hyperkalemia due to renin-angiotension-aldosterone system medications in patients treated for heart failure.MedDRA version: 21.0Level: PTClassification code 10005725Term: Blood potassium increasedSystem Organ Class: 10022891 - InvestigationsTherapeutic area: Not possible to specify
- Registration Number
- EUCTR2018-005030-38-HU
- Lead Sponsor
- Relypsa, Inc., a Vifor Company
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 2388
1. Subject provides written informed consent prior to study participation
2. Age at least 18 years or greater
3. History of New York Heart Association (NYHA) Class II–IV HF
4. Left ventricular ejection fraction <40%, measured by any echocardiographic,
radionuclide, or computerized tomography method in the last 12 months without
subsequent measured ejection fraction =40% during this interval)
5. Receiving any dose of a beta blocker (BB) for the treatment of HF or unable to
tolerate BB (reason documented)
6.Estimated glomerular filtration rate (eGFR) =30 mL/min/1.73 m2 at Screening
(based on a single local laboratory calculation using the Chronic Kidney Disease
Epidemiology Collaboration (CKD-EPI) equation; see Section 9.2 of the protocol)
7. Hyperkalemia at Screening (defined by 2 local serum K+ values of >5.0 mEq/L
each obtained from a separate venipuncture, e.g., one in each arm) while receiving ACEi, ARB, ARNi, and/or MRA,
OR
Normokalemia at Screening (serum K+ 4.0–5.0 mEq/L) with a history of hyperkalemia documented by a usual care serum K+ measurement >5.0 mEq/L while on RAASi treatment in the 12 months prior to Screening with a subsequent dose decrease or discontinuation of one or more RAASi medications
8. Females of child-bearing potential must be non-lactating, must have a negative
pregnancy test at Screening, and must agree to continue using contraception (see Section 9.8 of the protocol) throughout the study and for 4 weeks after study completion
9. Hospitalization for HF or equivalent (e.g., urgent emergency room or outpatient visit for worsening HF during which the patient received intravenous medications for the treatment of HF) within last 12 months
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1194
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1194
1.Current acute decompensated HF. Subjects with a discharge from a hospitalization for acute decompensation of HF at least 4 weeks before Screening
may be included
2. Symptomatic hypotension or systolic blood pressure <90 mmHg
3. Significant primary aortic or mitral valvular heart disease (except mitral
regurgitation due to left ventricular dilatation)
4. Heart transplantation or planned heart transplantation (i.e., currently on a heart transplant list) during the study period
5. Diagnosis of peripartum or chemotherapy-induced cardiomyopathy or acute
myocarditis in the previous 12 months
6. Implantation of a cardiac resynchronization therapy device in the previous
4 weeks
7. Restrictive, constrictive, hypertrophic, or obstructive cardiomyopathy
8. Untreated ventricular arrhythmia with syncope in the previous 4 weeks
9. History of, or current diagnosis of, a severe swallowing disorder, moderate-to-severe gastroparesis, or major gastrointestinal (GI) surgery (e.g., bariatric surgery or large bowel resection)
10. A major CV event within 4 weeks prior to Screening, including acute myocardial infarction, stroke (or transient ischemic attack), a life-threatening atrial or ventricular arrhythmia, or resuscitated cardiac arrest.
11. Brain natriuretic peptide (BNP) <125 pcg/mL or N-terminal pro b-type brain
natriuretic peptide (NT-proBNP) of <500 pcg/mL
12. Liver enzymes (alanine aminotransferase, aspartate aminotransferase) >5 times upper limit of normal at Screening based on the local laboratory
13. Diagnosis or treatment of a malignancy in the past 2 years, excluding
non-melanoma skin cancer and carcinoma in situ of the cervix, or a condition
highly likely to transform into a malignancy during the study
14. Presence of any condition (e.g., drug/alcohol abuse; acute illness), in the opinion of the Investigator, that places the subject at undue risk, or prevents complete participation in the trial procedures, or potentially jeopardizes the quality of the study data
15. Use of any investigational product for an unapproved indication within 1 month prior to Screening or currently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
16. Known hypersensitivity to patiromer (RLY5016) or its components
17. Prior use of commercial patiromer or previous participation in a study assessing patiromer
18. Subjects currently being treated with or having taken any one of the following medications in the 7 days prior to Screening: sodium or calcium polystyrene sulfonate or sodium zirconium cyclosilicate
19. An employee of Relypsa, Vifor Pharma, investigational site or the contract
research organization (CRO)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine if patiromer treatment of subjects who developed hyperkalemia while receiving RAASi medications will result in continued use of RAASi medications in accordance with heart failure (HF) treatment guidelines and thereby decrease the occurrence of the combined endpoint of cardiovascular (CV) death and CV hospitalization events compared with placebo treatment.;Secondary Objective: Not applicable. ;Primary end point(s): Time to first occurrence of CV death or CV hospitalization (or equivalent in outpatient clinic);Timepoint(s) of evaluation of this end point: See endpoint description.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): •Proportion of subjects on =50% of guideline-recommended target dose of ACEi,<br>ARB, or ARNi and =50% of guideline-recommended target dose of MRA at the<br>End of Study (EoS) Visit<br>• Total HF hospitalizations (or equivalent in outpatient clinic)<br>• Patient reported outcome: Kansas City Cardiomyopathy Questionnaire (KCCQ);Timepoint(s) of evaluation of this end point: See endpoint description.