RELieving Increasing oEdema Due to Heart Failure (RELIEHF)
Heart Failure,Congestive
About this trial
This is an interventional treatment trial for Heart Failure,Congestive
Eligibility Criteria
Inclusion Criteria
A. For the Screening Log (no follow-up envisaged nor linkage to electronic medical records)
- ≥18 years
- Heart failure in the investigators opinion (new onset or decompensated chronic heart failure)
- Planned to receive>80mg/day of furosemide or equivalent (IV, SC or oral) in the next 24 hours.
Worsening symptoms & signs of congestion in the prior 10 days requiring at least one of the following:
- hospitalisation
- administration of intravenous diuretics
- an increase in the dose of loop diuretic by at least 40mg/day of furosemide (or equivalent) to a total of at least 80mg/day of furosemide (or equivalent)
- addition of a thiazide diuretic to treatment with a loop diuretic
B. For the Consented Registry (with linkage to electronic medical records)
- Fulfils the criteria for the screening log
- Able and willing to provide written informed consent for registry participation
C. For Randomised Trial Run-in
- Fulfils criteria for the consented registry
- Clinical diagnosis of heart failure for at least 4 weeks
Congestion as shown by at least one of the following:
- Peripheral oedema
- Raised venous pressure
- Inferior vena cava diameter >20mm
Cardiac dysfunction documented by at least one of the following in the previous three years:
- A LVEF<50%or a report of moderate or severe left ventricular dysfunction
- Left atrial diameter >3.0cm/m2 (body surface area)
- Elevated BNP or NT-proBNP (BNP >150ng/L if in sinus rhythm or >450ng/L if not in sinus rhythm; NT-proBNP >500ng/L if in sinus rhythm and >1500ng/L if not in sinus rhythm)
- Able and willing to provide written informed consent for the randomised trial
D. For Randomisation
Serum potassium >5.0mmol/L
- Patients with a serum potassium >5.0mmol/L may be randomised immediately unless they have severe hyperkalaemia requiring, in the investigators opinion, intravenous treatment or a potassium binding agent.
- Severe hyperkalaemia should be managed according to the UK Renal Association guidelines of 2014 (https://renal.org/wp-content/uploads/2017/06/hyperkalaemia-guideline-1.pdf). Participants may be reconsidered for the trial once such interventions are no longer considered necessary.
- Patients with a serum potassium ≤5.0mmol/L should be initiated on spironolactone or have the dose increased up to 100mg/day and randomised only if serum potassium exceeds 5.0mmol/L. Those intolerant of or unwilling to take spironolactone should be offered eplerenone titrated to a maximum dose of 50mg/day.
- A run-in period of up to 35 days is permitted (the run-in period will usually occur during hospitalisation or a course of day-care or intense management).
After ingestion of a test-dose of patiromer,
- the patient is willing to continue in the trial
the investigator considers the patient can follow instructions on preparing patiromer
Exclusion criteria
A, For the Screening Log & Registry
- None
B. For the Randomised Trial
- eGFR <30ml/minute/1.73m2 (if clinically appropriate, the dose of other agents such as loop diuretics, ACE inhibitors, angiotensin receptor blockers, beta-blockers and sacubitril-valsartan may be adjusted to allow eGFR to increase)
- Systolic BP <90mmHg
- Uncorrected valve disease as the main cause of heart failure in the investigators opinion
- Hepatic encephalopathy or known severe liver disease
- Infection currently requiring intravenous antibiotics or temperature >38°C
- Myocardial ischaemia currently requiring intravenous therapy or coronary intervention in the previous 7 days
- Arrhythmia requiring urgent cardioversion or intravenous therapy
- Severe hyperkalaemia requiring, in the investigator's opinion, intravenous treatment or a potassium-binding agent
- The patient is already receiving a potassium-binding agent (this includes patiromer) or the treating physician has already decided to use one
- Known hypersensitivity to patiromer or any of the excipients
- Known intolerance to both spironolactone and eplerenone (not including hyperkalaemia)
- Known hypersensitivity to the active substance or excipients of spironolactone and eplerenone as per the current Summary of Product Characteristics (Note: actual medicine supplied to participants will vary depending on local arrangements)
- Women of childbearing potential. For the purposes of this trial this means any woman aged <60 years unless they have had a hysterectomy or bilateral tubal ligation or are aged >50 years and have undergone the menopause and had amenorrhea for at least 3 years
Patients taking the following systemic medicines:
- strong inhibitors of CYP 3A4 (e.g. itraconazole, ketoconazole, ritonavir, nelfinavir, clarithromycin, telithromycin and nefazodone)
- Lithium
- Tacrolimus or Cyclosporin
- The combination of an angiotensin converting enzyme (ACE) inhibitor and an angiotensin receptor blocker (ARB)
- Rare hereditary problems of galactose or fructose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
- Known amyloid heart disease
- Cancer likely to cause death or major disability within the next three years
- Patients requiring mechanical circulatory support and
- Patients who do not develop a serum potassium >5.0mmol/L despite receiving up to 100mg/day of spironolactone or 50mg/day of eplerenone during the run in phase.
Sites / Locations
- Glasgow Royal Infirmary
- Basildon University Hospital
- Blackpool Victoria Hospital
- Princess of Wales Hospital
- Royal Devon and Exeter Hospital
- Queen Elizabeth University Hospital
- Castle Hill Hospital
- Victoria Hospital
- Guy's and St Thomas's Hospital
- King's College Hospital
- St George's Hospital
Arms of the Study
Arm 1
Arm 2
No Intervention
Experimental
Standard dose MRA
Patiromer and high dose MRA
Participants in this arm will have titration to guideline-recommended doses of MRA attempted.
Participants assigned to patiromer may be titrated to 200mg/day spironolactone or the highest licensed dose of eplerenone (50mg/day).