RELieving Increasing oEdema Due to Heart Failure

NCT ID: NCT04142788

Last Updated: 2025-03-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-26
• Study Completion Date: 2022-12-20

Brief Summary

This trial will investigate the potential for patiromer-facilitated use of higher doses of mineralocorticoid antagonists in addition to standard care (compared to standard care alone) to improve congestion, well-being and mortality in people who have worsening congestion due to heart failure and hyperkalaemia.

Detailed Description

People with worsening congestive heart failure may benefit from treatment with higher doses of MRA if they are administered patiromer to treat or prevent hyperkalaemia.

Potential participants with worsening heart failure will be identified by their care teams and asked to participate in a research registry. If eligible, registry participants will be asked to take part in the RELIEHF randomised trial.

The randomised trial will investigate whether patiromer allows patients with worsening heart failure to be titrated to higher doses of MRA (predominantly spironolactone). Participants assigned to patiromer may be titrated to 200mg/day spironolactone or the highest licensed dose of eplerenone (50mg/day). Participants who are not assigned to patiromer should have titration to guideline-recommended doses of MRA attempted.

The registry and trial will take place in about 100 secondary care sites across the UK. At the end of the trial, participants will be followed through their electronic medical records via record linkage for up to 10 years

Conditions

Heart Failure，Congestive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Standard dose MRA

Participants in this arm will have titration to guideline-recommended doses of MRA attempted.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Patiromer and high dose MRA

Participants assigned to patiromer may be titrated to 200mg/day spironolactone or the highest licensed dose of eplerenone (50mg/day).

Group Type: EXPERIMENTAL

Patiromer

Intervention Type: DRUG

Patiromer (8.4g/day to 25.2g/day) and spironolactone (up to 200mg/day) or eplerenone (up to 50mg/day if spironolactone not acceptable). Treatments should be titrated to maintain serum potassium close to the target of 4.5mmol/L.

Interventions

Patiromer

Patiromer (8.4g/day to 25.2g/day) and spironolactone (up to 200mg/day) or eplerenone (up to 50mg/day if spironolactone not acceptable). Treatments should be titrated to maintain serum potassium close to the target of 4.5mmol/L.

Intervention Type: DRUG

Other Intervention Names

Veltassa

Eligibility Criteria

Inclusion Criteria

A. For the Screening Log (no follow-up envisaged nor linkage to electronic medical records)

1. ≥18 years

2. Heart failure in the investigators opinion (new onset or decompensated chronic heart failure)

3. Planned to receive>80mg/day of furosemide or equivalent (IV, SC or oral) in the next 24 hours.

4. Worsening symptoms & signs of congestion in the prior 10 days requiring at least one of the following:

1. hospitalisation

2. administration of intravenous diuretics

3. 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)

4. addition of a thiazide diuretic to treatment with a loop diuretic

B. For the Consented Registry (with linkage to electronic medical records)

1. Fulfils the criteria for the screening log

2. Able and willing to provide written informed consent for registry participation

C. For Randomised Trial Run-in

1. Fulfils criteria for the consented registry

2. Clinical diagnosis of heart failure for at least 4 weeks

3. Congestion as shown by at least one of the following:

1. Peripheral oedema

2. Raised venous pressure

3. Inferior vena cava diameter >20mm

4. Cardiac dysfunction documented by at least one of the following in the previous three years:

1. A LVEF<50%or a report of moderate or severe left ventricular dysfunction

2. Left atrial diameter >3.0cm/m2 (body surface area)

3. 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)

5. Able and willing to provide written informed consent for the randomised trial

D. For Randomisation

1. 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).

2. After ingestion of a test-dose of patiromer,

1. the patient is willing to continue in the trial

2. 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

1. 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)

2. Systolic BP <90mmHg

3. Uncorrected valve disease as the main cause of heart failure in the investigators opinion

4. Hepatic encephalopathy or known severe liver disease

5. Infection currently requiring intravenous antibiotics or temperature >38°C

6. Myocardial ischaemia currently requiring intravenous therapy or coronary intervention in the previous 7 days

7. Arrhythmia requiring urgent cardioversion or intravenous therapy

8. Severe hyperkalaemia requiring, in the investigator's opinion, intravenous treatment or a potassium-binding agent

9. The patient is already receiving a potassium-binding agent (this includes patiromer) or the treating physician has already decided to use one

10. Known hypersensitivity to patiromer or any of the excipients

11. Known intolerance to both spironolactone and eplerenone (not including hyperkalaemia)

12. 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)

13. 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

14. 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

15. The combination of an angiotensin converting enzyme (ACE) inhibitor and an angiotensin receptor blocker (ARB)

16. Rare hereditary problems of galactose or fructose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption

17. Known amyloid heart disease

18. Cancer likely to cause death or major disability within the next three years

19. Patients requiring mechanical circulatory support and

20. 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Glasgow

OTHER

Sponsor Role: collaborator

NHS Greater Glasgow and Clyde

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John Cleland

Role: PRINCIPAL_INVESTIGATOR

University of Glasgow

Locations

Glasgow Royal Infirmary

Glasgow, Strathclyde, United Kingdom

Basildon University Hospital

Basildon, , United Kingdom

Blackpool Victoria Hospital

Blackpool, , United Kingdom

Princess of Wales Hospital

Bridgend, , United Kingdom

Royal Devon and Exeter Hospital

Exeter, , United Kingdom

Queen Elizabeth University Hospital

Glasgow, , United Kingdom

Castle Hill Hospital

Hull, , United Kingdom

Victoria Hospital

Kirkcaldy, , United Kingdom

Guy's and St Thomas's Hospital

London, , United Kingdom

King's College Hospital

London, , United Kingdom

St George's Hospital

London, , United Kingdom

Countries

United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-003662-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GN17CA082

Identifier Type: -

Identifier Source: org_study_id