Trial Outcomes & Findings for RELieving Increasing oEdema Due to Heart Failure (NCT NCT04142788)
NCT ID: NCT04142788
Last Updated: 2025-03-04
Results Overview
To find out whether administering patiromer and higher-dose MRA improves evidence of congestion on Day 60 compared to standard care.
TERMINATED
PHASE4
19 participants
After 400 patients have been evaluated at Day 60
2025-03-04
Participant Flow
Participants were screened across 12 sites between 13/03/2020 and 16/03/2022. The first participant to the registry was consented on 26/08/2020 and the last participant was consented to the registry on 17/03/2022. Participants to the trial that successfully completed run-in were randomised between 14/10/2021 and 16/03/2022.
139 participants entered the registry but the trial was stopped because of low recruitment into the run-in phase (due, in part at least, the COVID pandemic), and because of the 19 patients who did enter the run-in phase, despite receiving up to spironolactone 100mg/day or eplerenone 50mg/day, only 4 patients developed a serum potassium \>5.0 mmol/L, which was a requirement to enter the randomised phase of the trial.
Participant milestones
| Measure |
Standard Dose MRA
Participants in this arm will have titration to guideline-recommended doses of MRA attempted.
|
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).
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.
|
|---|---|---|
|
Overall Study
STARTED
|
2
|
2
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
2
|
2
|
Reasons for withdrawal
| Measure |
Standard Dose MRA
Participants in this arm will have titration to guideline-recommended doses of MRA attempted.
|
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).
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.
|
|---|---|---|
|
Overall Study
Trial terminated prematurely
|
2
|
2
|
Baseline Characteristics
RELieving Increasing oEdema Due to Heart Failure
Baseline characteristics by cohort
| Measure |
Standard Dose MRA
n=2 Participants
Participants in this arm will have titration to guideline-recommended doses of MRA attempted.
|
Patiromer and High Dose MRA
n=2 Participants
Participants assigned to patiromer may be titrated to 200mg/day spironolactone or the highest licensed dose of eplerenone (50mg/day).
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.
|
Total
n=4 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
Age group (years) · <50
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Customized
Age group (years) · 50-60
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Age, Customized
Age group (years) · >60
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Ethnicity · White
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Ethnicity · Mixed/Multiple ethnic groups
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Ethnicity · Asian/Asian British
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Ethnicity · Black/African/Caribbean/Black British
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Ethnicity · Other ethnic group
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom · Scotland
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom · England
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom · Wales
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: After 400 patients have been evaluated at Day 60Population: Data were not collected due to early termination of the study.
To find out whether administering patiromer and higher-dose MRA improves evidence of congestion on Day 60 compared to standard care.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Through study completionPopulation: Data were not collected due to early termination of the study.
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.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Periodically up to 10 yearsPopulation: Data were not collected due to early termination of the study.
Composite of time to (re-)hospitalisation or death
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Days 7 and 60Population: Data were not collected due to early termination of the study.
Dose of MRA achieved for all trial participants
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Days 7 and 60Population: Data were not collected due to early termination of the study.
Congestion Index score for all trial participants
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Through 60 daysPopulation: Data were not collected due to early termination of the study.
Days dead or hospitalised during the first 60 days for all trial participants
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Days 7 and 60Population: Data were not collected due to early termination of the study.
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)
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Days 7 and 60Population: Data were not collected due to early termination of the study.
Quality of Life using validated KCCQ-12 questionnaire for all trial participants (score - min 0, max 100; higher means better outcome)
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Days 7 and 60Population: Data were not collected due to early termination of the study.
NYHA class (I-IV) for all trial participants
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Days 7 and 60Population: Data were not collected due to early termination of the study.
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)
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Through study completion, up to 5 yearsPopulation: Data were not collected due to early termination of the study.
All-cause mortality for all trial participants
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Through study completion, up to 5 yearsPopulation: Data were not collected due to early termination of the study.
Non-cancer mortality for all trial participants
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Through study completion, up to 5 yearsPopulation: Data were not collected due to early termination of the study.
Cardiovascular mortality for all trial participants
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: During first yearPopulation: Data were not collected due to early termination of the study.
Days lost to hospitalisation for heart failure or non-cancer deaths over 12 months for all trial participants
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: During first yearPopulation: Data were not collected due to early termination of the study.
Days lost to any hospitalisation or any death over 12 months for all trial participants
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Through study completion, up to 5 yearsPopulation: Data were not collected due to early termination of the study.
Quality adjusted life-years for duration of the trial for all trial participants
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: At 12 monthsPopulation: Data were not collected due to early termination of the study.
Proportion alive and well at 12 months (well-being defined by KCCQ-12 score) for all trial participants
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: At 6 months and 12 monthsPopulation: Data were not collected due to early termination of the study.
Dose of MRA for all trial participants
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: At 6 months and 12 monthsPopulation: Data were not collected due to early termination of the study.
Dose of oral diuretics other than MRA for all trial participants
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: At 6 months and 12 monthsPopulation: Data were not collected due to early termination of the study.
NYHA class (I-IV) for all trial participants
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: At 6 months and 12 monthsPopulation: Data were not collected due to early termination of the study.
Patient Global Assessment to measure quality of life for all trial participants
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Periodically up to 10 yearsPopulation: Data were not collected due to early termination of the study.
Time to cardiovascular (re-)hospitalisation or non-cancer death for registry/trial participants
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Periodically up to 10 yearsPopulation: Data were not collected due to early termination of the study.
Time to heart failure (re-)hospitalisation or non-cancer death for registry/trial participants
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Periodically up to 10 yearsPopulation: Data were not collected due to early termination of the study.
Incidence rate for hospitalisation for registry/trial participants
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Periodically up to 10 yearsPopulation: Data were not collected due to early termination of the study.
Time to death (all-causes, cardiovascular causes, heart failure causes, cancer causes, and other) for registry and trial participants
Outcome measures
Outcome data not reported
Adverse Events
Run-in and Not Randomised
Standard Dose MRA
Patiromer and High Dose MRA
Serious adverse events
| Measure |
Run-in and Not Randomised
n=15 participants at risk
Participants with a serum potassium \<=5.0mmol/L who are not currently receiving an MRA will first be given spironolactone (or eplerenone#) 25mg once daily and randomised to patiromer or not, if and when their serum potassium is \>5.0mmol/L. If serum potassium does not exceed 5.0mmol/L within 72 hours, the dose of spironolactone may be increased to 50mg/day and after a further 72 hours to 100mg/day. Those intolerant of or unwilling to take spironolactone should be offered eplerenone (maximum dose 50mg/day).
Participants with a serum potassium \<=5.0mmol/L who are currently receiving an MRA at a dose of \<50mg/day will be initiated on spironolactone 50mg once daily (or eplerenone#) or if currently already receiving 50mg/day, spironolactone 100mg/day (the maximum dose of eplerenone is 50mg/day). They will be randomised to receive patiromer or not, only once their serum potassium is \>5.0mmol/L.
\[# only those intolerant of, or unwilling to take, spironolactone should be offered eplerenone\]
|
Standard Dose MRA
n=2 participants at risk
Participants in this arm will have titration to guideline-recommended doses of MRA attempted.
|
Patiromer and High Dose MRA
n=2 participants at risk
Participants assigned to patiromer may be titrated to 200mg/day spironolactone or the highest licensed dose of eplerenone (50mg/day).
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.
|
|---|---|---|---|
|
Renal and urinary disorders
Acute kidney injury
|
6.7%
1/15 • Number of events 1 • 15 months due to early study termination
Serious Adverse Event data were collected for all individuals entering run-in, regardless of whether or not they were subsequently randomised. Other \[non-serious\] adverse events were not collected as part of the study for the Run-in and Not Randomised Arm.
|
50.0%
1/2 • Number of events 1 • 15 months due to early study termination
Serious Adverse Event data were collected for all individuals entering run-in, regardless of whether or not they were subsequently randomised. Other \[non-serious\] adverse events were not collected as part of the study for the Run-in and Not Randomised Arm.
|
50.0%
1/2 • Number of events 1 • 15 months due to early study termination
Serious Adverse Event data were collected for all individuals entering run-in, regardless of whether or not they were subsequently randomised. Other \[non-serious\] adverse events were not collected as part of the study for the Run-in and Not Randomised Arm.
|
|
Investigations
Cystoscopy
|
0.00%
0/15 • 15 months due to early study termination
Serious Adverse Event data were collected for all individuals entering run-in, regardless of whether or not they were subsequently randomised. Other \[non-serious\] adverse events were not collected as part of the study for the Run-in and Not Randomised Arm.
|
0.00%
0/2 • 15 months due to early study termination
Serious Adverse Event data were collected for all individuals entering run-in, regardless of whether or not they were subsequently randomised. Other \[non-serious\] adverse events were not collected as part of the study for the Run-in and Not Randomised Arm.
|
50.0%
1/2 • Number of events 1 • 15 months due to early study termination
Serious Adverse Event data were collected for all individuals entering run-in, regardless of whether or not they were subsequently randomised. Other \[non-serious\] adverse events were not collected as part of the study for the Run-in and Not Randomised Arm.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
6.7%
1/15 • Number of events 1 • 15 months due to early study termination
Serious Adverse Event data were collected for all individuals entering run-in, regardless of whether or not they were subsequently randomised. Other \[non-serious\] adverse events were not collected as part of the study for the Run-in and Not Randomised Arm.
|
0.00%
0/2 • 15 months due to early study termination
Serious Adverse Event data were collected for all individuals entering run-in, regardless of whether or not they were subsequently randomised. Other \[non-serious\] adverse events were not collected as part of the study for the Run-in and Not Randomised Arm.
|
0.00%
0/2 • 15 months due to early study termination
Serious Adverse Event data were collected for all individuals entering run-in, regardless of whether or not they were subsequently randomised. Other \[non-serious\] adverse events were not collected as part of the study for the Run-in and Not Randomised Arm.
|
Other adverse events
| Measure |
Run-in and Not Randomised
n=15 participants at risk
Participants with a serum potassium \<=5.0mmol/L who are not currently receiving an MRA will first be given spironolactone (or eplerenone#) 25mg once daily and randomised to patiromer or not, if and when their serum potassium is \>5.0mmol/L. If serum potassium does not exceed 5.0mmol/L within 72 hours, the dose of spironolactone may be increased to 50mg/day and after a further 72 hours to 100mg/day. Those intolerant of or unwilling to take spironolactone should be offered eplerenone (maximum dose 50mg/day).
Participants with a serum potassium \<=5.0mmol/L who are currently receiving an MRA at a dose of \<50mg/day will be initiated on spironolactone 50mg once daily (or eplerenone#) or if currently already receiving 50mg/day, spironolactone 100mg/day (the maximum dose of eplerenone is 50mg/day). They will be randomised to receive patiromer or not, only once their serum potassium is \>5.0mmol/L.
\[# only those intolerant of, or unwilling to take, spironolactone should be offered eplerenone\]
|
Standard Dose MRA
n=2 participants at risk
Participants in this arm will have titration to guideline-recommended doses of MRA attempted.
|
Patiromer and High Dose MRA
n=2 participants at risk
Participants assigned to patiromer may be titrated to 200mg/day spironolactone or the highest licensed dose of eplerenone (50mg/day).
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.
|
|---|---|---|---|
|
Surgical and medical procedures
Cardioversion
|
—
0/0 • 15 months due to early study termination
Serious Adverse Event data were collected for all individuals entering run-in, regardless of whether or not they were subsequently randomised. Other \[non-serious\] adverse events were not collected as part of the study for the Run-in and Not Randomised Arm.
|
0.00%
0/2 • 15 months due to early study termination
Serious Adverse Event data were collected for all individuals entering run-in, regardless of whether or not they were subsequently randomised. Other \[non-serious\] adverse events were not collected as part of the study for the Run-in and Not Randomised Arm.
|
50.0%
1/2 • Number of events 1 • 15 months due to early study termination
Serious Adverse Event data were collected for all individuals entering run-in, regardless of whether or not they were subsequently randomised. Other \[non-serious\] adverse events were not collected as part of the study for the Run-in and Not Randomised Arm.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place