A Multicenter, Double-blind, Placebo-controlled, Randomized Withdrawal, Parallel Group Study of Patiromer for the Management of Hyperkalemia in Subjects Receiving Renin-Angiotensin-Aldosterone System Inhibitor (RAASi) Medications for the Treatment of Heart Failure (DIAMOND)
- Conditions
- Blood potassium increasedHyperkalemia / high potassium in the blood
- Registration Number
- NL-OMON55106
- Lead Sponsor
- Relypsa, Inc., a Vifor Company
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 82
1. Subject provides written informed consent prior to study participation
2. Age at least 18 years or greater
3. Current New York Heart Association (NYHA) Class II-IV
4. Left ventricular ejection fraction <=40%, measured by any echocardiographic,
radionuclide, magnetic resonance imaging (MRI), angiographic, 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 analysis of serum creatinine and
calculation using the Chronic Kidney Disease Epidemiology Collaboration
(CKD-EPI) equation; see Section 9.2)
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 or two
separate venipunctures in the same arm) while receiving ACEi, ARB, ARNi, and/or
MRA
OR
Normokalemia at Screening (defined by 2 local serum K+ >=4.0 <=5.0 mEq/L each
obtained from a separate venipuncture, e.g., one in each arm or two separate
venipunctures in the same arm) but 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 leading to a subsequent and permanent 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) throughout the study and for 4 weeks after
study completion
9. With hospitalization for HF or equivalent (e.g., emergency room or
outpatient visit for worsening HF during which the patient received intravenous
medications for the treatment of HF) within the last 12 months before Screening
a) Without atrial fibrillation at Screening, BNP level must be greater than 150
pcg/mL (18 pmol/L) or N-terminal pro b-type BNP (NT proBNP) must be greater
than 600 pcg/mL (71 pmol/L)
b) With atrial fibrillation at Screening, BNP level must be greater than 300
pcg/mL (35 pmol/L) or NT proBNP must be greater than 1,200 pcg/mL (142 pmol/L)
OR
Without hospitalization for HF or equivalent (e.g., emergency room or
outpatient visit for worsening HF during which the subject received intravenous
medications for the treatment of HF) within the last 12 months before Screening
a) Without atrial fibrillation at Screening, BNP level must be greater than 300
pcg/mL (35 pmol/L) or NT proBNP must be greater than 1,200 pcg/mL (142 pmol/L)
b) With atrial fibrillation at Screening, BNP level must be greater than 600
pcg/mL (71 pmol/L) or NT proBNP must be greater than 2400 pcg/mL (284 pmol/L)
1. Current acute decompensated HF within 4 weeks before Screening. Subjects
with a discharge from a hospitalization for acute decompensation of HF longer
than 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
secondary mitral regurgitation due to left ventricular dilatation)
4. Heart transplantation or planned heart transplantation (i.e., currently on a
heart transplant waiting 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 before Screening
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. Note: This exclusion criterion is included in the new Inclusion Criterion 9
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, prostate cancer with
Gleason score <7, 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 4
weeks 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. Note: This exclusion criterion is modified and partially incorporated in
Exclusion Criterion 18
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, or patiromer
19. An employee, spouse, or family member of the Sponsor (Relypsa, Vifor
Pharma), investigational site or the Contract Research Organization (CRO)
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Time to first occurrence of CV death or CV hospitalization</p><br>
- Secondary Outcome Measures
Name Time Method <p>• Proportion of subjects on >=50% of guideline-recommended target dose of ACEi,<br /><br>ARB, or ARNi and >=50% of guideline-recommended target dose of MRA at the EoS<br /><br>Visit<br /><br>• Total HF hospitalizations (or equivalent in outpatient clinic)<br /><br>• Change from randomization in the clinical summary score of Kansas City<br /><br>Cardiomyopathy Questionnaire (KCCQ) at 8 months</p><br>