Heart Failure，CongestivePhase 4RELIEHFNCT04142788
RELieving Increasing oEdema Due to Heart Failure
A Phase 4 study testing Patiromer in people with Heart Failure，Congestive, run by NHS Greater Glasgow and Clyde at 11 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure，Congestive
- What is being tested?
- Patiromer
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 11 sitesUnited Kingdom
- Study dates
- 26 Aug 2020to 20 Dec 2022
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 33Show fewer
- 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
- 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
- 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
- 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
Who cannot join
- A, For the Screening Log \& Registry
- None
- 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
Show all 26Show fewer
- 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.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United Kingdom11 sites
Basildon University Hospital
Basildon
Blackpool Victoria Hospital
Blackpool
Princess of Wales Hospital
Bridgend
Royal Devon and Exeter Hospital
Exeter
Glasgow Royal Infirmary
Glasgow, Strathclyde, G4 0SF
Queen Elizabeth University Hospital
Glasgow
Castle Hill Hospital
Hull
Victoria Hospital
Kirkcaldy
Guy's and St Thomas's Hospital
London
King's College Hospital
London
St George's Hospital
London
About this study
Official title: A Phase IV, Registry-based, Randomised, Controlled, Open-label Trial Investigating the Potential for Patiromer-facilitated Use of Higher Doses of MRAs in Addition to Standard Care to Improve Congestion, Well-being, Morbidity and Mortality
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.
Read the 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
- Being tested
- Patiromer
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PatiromerDrug
Also called Veltassa
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.
| Study group | Role | What they receive |
|---|---|---|
| Standard dose MRA | No intervention | Participants in this arm will have titration to guideline-recommended doses of MRA attempted. |
| Patiromer and high dose MRA | Experimental | Participants assigned to patiromer may be titrated to 200mg/day spironolactone or the highest licensed dose of eplerenone (50mg/day). Receives: Drug: Patiromer |
What is being measured
The primary outcome is the main question the study is designed to answer.
"Congestion Index" on Day 60
To find out whether administering patiromer and higher-dose MRA improves evidence of congestion on Day 60 compared to standard care.
Measured: After 400 patients have been evaluated at Day 60
Morbidity/Mortality
Composite of time to need for parenteral diuretic therapy (subsequent to initial discharge) for worsening or recalcitrant heart failure, (re-)hospitalisation for worsening heart failure or non-cancer deaths.
Measured: Through study completion
Morbidity and Mortality
Composite of time to (re-)hospitalisation or death
Measured: Periodically up to 10 years
Secondary outcomes (22)
Dose of MRA
Dose of MRA achieved for all trial participants
Measured: Days 7 and 60
Congestion Index
Congestion Index score for all trial participants
Measured: Days 7 and 60
Days Dead or Hospitalised During the First 60 Days
Days dead or hospitalised during the first 60 days for all trial participants
Measured: Through 60 days
Quality of Life (EQ-5D)
Quality of Life using validated EQ-5D questionnaire for all trial participants (visual analogue score - min 0, max 100, higher means better outcome; calculated score min 0, max 1, higher means better outcome)
Measured: Days 7 and 60
Quality of Life Kansas City Cardiomyopathy Questionnaire (KCCQ-12)
Quality of Life using validated KCCQ-12 questionnaire for all trial participants (score - min 0, max 100; higher means better outcome)
Measured: Days 7 and 60
NYHA Class
NYHA class (I-IV) for all trial participants
Measured: Days 7 and 60
Patient Global Assessment
Patient Global Assessment to measure quality of life for all trial participants (ranges from markedly improved to markedly worsened; markedly improved means a better outcome)
Measured: Days 7 and 60
Reduced All-cause Mortality
All-cause mortality for all trial participants
Measured: Through study completion, up to 5 years
Reduced Non-cancer Mortality
Non-cancer mortality for all trial participants
Measured: Through study completion, up to 5 years
Reduced Cardiovascular Mortality
Cardiovascular mortality for all trial participants
Measured: Through study completion, up to 5 years
Reduced Mortality/Morbidity - HF/Non-cancer
Days lost to hospitalisation for heart failure or non-cancer deaths over 12 months for all trial participants
Measured: During first year
Reduced Mortality/Morbidity - Any
Days lost to any hospitalisation or any death over 12 months for all trial participants
Measured: During first year
QALY
Quality adjusted life-years for duration of the trial for all trial participants
Measured: Through study completion, up to 5 years
Proportion Alive and Well at 12 Months
Proportion alive and well at 12 months (well-being defined by KCCQ-12 score) for all trial participants
Measured: At 12 months
Dose of MRA
Dose of MRA for all trial participants
Measured: At 6 months and 12 months
Dose of Oral Diuretics Other Than MRA
Dose of oral diuretics other than MRA for all trial participants
Measured: At 6 months and 12 months
NYHA Class
NYHA class (I-IV) for all trial participants
Measured: At 6 months and 12 months
Patient Global Assessment
Patient Global Assessment to measure quality of life for all trial participants
Measured: At 6 months and 12 months
Participant Characteristics and Assessment of Morbidity and Mortality
Time to cardiovascular (re-)hospitalisation or non-cancer death for registry/trial participants
Measured: Periodically up to 10 years
Participant Characteristics/Assessment of Morbidity/Mortality
Time to heart failure (re-)hospitalisation or non-cancer death for registry/trial participants
Measured: Periodically up to 10 years
Characteristics and Assessment of Morbidity/Mortality
Incidence rate for hospitalisation for registry/trial participants
Measured: Periodically up to 10 years
Characteristics/Assessment of Morbidity/Mortality
Time to death (all-causes, cardiovascular causes, heart failure causes, cancer causes, and other) for registry and trial participants
Measured: Periodically up to 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2019
- Study start26 Aug 2020
- Primary completion20 Dec 2022
- Study completion20 Dec 2022
Why it stopped: The study was stopped due to low recruitment, which the Steering Committee and funder agreed could not be rectified.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Heart Failure，CongestiveStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- NHS Greater Glasgow and Clyde
- Sponsor type
- University, hospital or other
- Collaborators
- University of Glasgow
- Responsible party
- Sponsor
- Investigators
- John Cleland, Principal investigator, University of Glasgow
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04142788
- Sponsor's protocol ID
- GN17CA082
- Other IDs
- 2018-003662-14, 2018
- Acronym
- RELIEHF
- Status last verified
- Dec 2024
- First submitted
- 8 Oct 2019
- Last updated
- 4 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IV, Registry-based, Randomised, Controlled, Open-label Trial Investigating the Potential for Patiromer-facilitated Use of Higher Doses of MRAs in Addition to Standard Care to Improve Congestion, Well-being, Morbidity and Mortality
- ClinicalTrials.gov ID
- NCT04142788
- Acronym / sponsor ID
- RELIEHF / GN17CA082
- Conditions
- Heart Failure，Congestive
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was stopped due to low recruitment, which the Steering Committee and funder agreed could not be rectified.
- Enrolment
- 19 participants (actual)
- Lead sponsor
- NHS Greater Glasgow and ClydeUniversity, hospital or other
- Collaborators
- University of Glasgow
- Study start
- 26 Aug 2020 (actual)
- Primary completion
- 20 Dec 2022 (actual)
- Study completion
- 20 Dec 2022 (actual)
- First posted
- 29 Oct 2019 (actual)
- Results
- Posted 4 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard dose MRA | No intervention | –Participants in this arm will have titration to guideline-recommended doses of MRA attempted. |
| Patiromer and high dose MRA | Experimental | Drug: PatiromerParticipants assigned to patiromer may be titrated to 200mg/day spironolactone or the highest licensed dose of eplerenone (50mg/day). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (33 listed)
- 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:
Key exclusion criteria (26 listed)
- A, For the Screening Log \& Registry
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PatiromerAlso: VeltassaPatiromer (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. | Drug | Patiromer and high dose MRA |
Primary outcome
"Congestion Index" on Day 60
Time frame: After 400 patients have been evaluated at Day 60
To find out whether administering patiromer and higher-dose MRA improves evidence of congestion on Day 60 compared to standard care.
Morbidity/Mortality
Time frame: Through study completion
Composite of time to need for parenteral diuretic therapy (subsequent to initial discharge) for worsening or recalcitrant heart failure, (re-)hospitalisation for worsening heart failure or non-cancer deaths.
Morbidity and Mortality
Time frame: Periodically up to 10 years
Composite of time to (re-)hospitalisation or death
22 secondary outcomes
Dose of MRA
Time frame: Days 7 and 60
Congestion Index
Time frame: Days 7 and 60
Days Dead or Hospitalised During the First 60 Days
Time frame: Through 60 days
Quality of Life (EQ-5D)
Time frame: Days 7 and 60
Quality of Life Kansas City Cardiomyopathy Questionnaire (KCCQ-12)
Time frame: Days 7 and 60
NYHA Class
Time frame: Days 7 and 60
Patient Global Assessment
Time frame: Days 7 and 60
Reduced All-cause Mortality
Time frame: Through study completion, up to 5 years
Reduced Non-cancer Mortality
Time frame: Through study completion, up to 5 years
Reduced Cardiovascular Mortality
Time frame: Through study completion, up to 5 years
Reduced Mortality/Morbidity - HF/Non-cancer
Time frame: During first year
Reduced Mortality/Morbidity - Any
Time frame: During first year
QALY
Time frame: Through study completion, up to 5 years
Proportion Alive and Well at 12 Months
Time frame: At 12 months
Dose of MRA
Time frame: At 6 months and 12 months
Dose of Oral Diuretics Other Than MRA
Time frame: At 6 months and 12 months
NYHA Class
Time frame: At 6 months and 12 months
Patient Global Assessment
Time frame: At 6 months and 12 months
Participant Characteristics and Assessment of Morbidity and Mortality
Time frame: Periodically up to 10 years
Participant Characteristics/Assessment of Morbidity/Mortality
Time frame: Periodically up to 10 years
Characteristics and Assessment of Morbidity/Mortality
Time frame: Periodically up to 10 years
Characteristics/Assessment of Morbidity/Mortality
Time frame: Periodically up to 10 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Heart Failure，Congestive
RecruitingPhase 2/3
Efficacy, Safety, and Pharmacokinetics of Vericiguat in Pediatric Participants With Heart Failure Due to Left Ventricular Systolic Dysfunction (MK-1242-036)
Heart Failure, Left Ventricular Systolic Dysfunction
RecruitingPhase 1/2
HS235 Study in Overweight and Obese Participants With Combined Pre and Post-Capillary Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction
Pulmonary Hypertension, Heart Failure With Preserved Ejection Fraction
Active, not recruiting
Heart Failure Patient Management and Interventions Using Continuous Patient Monitoring Outside Hospitals and Real-world Data
Chronic Heart Failure, Heart Transplant Recipient
Enrolling by invitationObservational study
Multi-Scale Analysis of Phenotypes in Heart Failure (MAP-HEART)
Heart Failure
Not yet recruitingObservational study
Real-world Effectiveness and Safety of Savagen (Sacubitril/Valsartan) in Malaysian HFrEF Patients
Heart Failure With Reduced Ejection Fraction (HFrEF), Heart Failure
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Cleland principal investigator
University of Glasgow
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Patiromer in people with Heart Failure，Congestive, run by NHS Greater Glasgow and Clyde at 11 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 33 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
"Congestion Index" on Day 60 (time frame: After 400 patients have been evaluated at Day 60). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2025.