Trial Outcomes & Findings for Patiromer for the Management of Hyperkalemia in Subjects Receiving RAASi Medications for the Treatment of Heart Failure (DIAMOND) (NCT NCT03888066)
NCT ID: NCT03888066
Last Updated: 2023-02-24
Results Overview
Adjusted mean changes in serum K+ from Baseline.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1195 participants
Primary outcome timeframe
Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
Results posted on
2023-02-24
Participant Flow
From a total of 1642 screened participants, 1195 entered the Run-in Phase. The Run-in Phase Set includes participants who signed the informed consent and received at least 1 dose of patiromer during the Run-in Phase but were not eligible to be randomized. A total of 1168 participants received patiromer during Run-in Phase, and 878 of these participants were randomized to receive patiromer or placebo during the Treatment Phase
Participant milestones
| Measure |
Patiromer
Randomized participants who received a daily dose of patiromer, with possible dose adjustments based on subsequent local serum potassium level, during the Treatment Phase.
The starting dose of patiromer was 1 packet/day taken either with food or without food. Based upon the K+ management algorithms, patiromer was to be increased by 1 packet per day in intervals of at least 1 week (±3 days). If hypokalemia developed during the Treatment Phase, then the study drug was to be down titrated (lowest acceptable dose was 0 packets/day) until local serum K+ ≥4.0 mEq/l. Doses of patiromer were 0 packets/day, 1 packet/day, 2 packets/day, and 3 packets/day (maximum dose).
mEq/l = Milliequivalents Per Liter
|
Placebo
Randomized participants who received a daily dose of placebo, with possible dose adjustments based on subsequent local serum potassium level, during the Treatment Phase.
The starting dose of placebo was 1 packet/day taken either with food or without food. Based upon the K+ management algorithms, placebo was to be increased by 1 packet per day in intervals of at least 1 week (±3 days). If hypokalemia developed during the Treatment Phase, then the study drug was to be down-titrated (lowest acceptable dose was 0 packets/day) until local serum K+ ≥4.0 mEq/l. Doses of placebo were 0 packets/day, 1 packet/day, 2 packets/day, and 3 packets/day (maximum dose).
mEq/l = Milliequivalents Per Liter
|
|---|---|---|
|
Run-in Phase
STARTED
|
1195
|
0
|
|
Run-in Phase
COMPLETED
|
878
|
0
|
|
Run-in Phase
NOT COMPLETED
|
317
|
0
|
|
Treatment Phase (Overall Study)
STARTED
|
439
|
439
|
|
Treatment Phase (Overall Study)
COMPLETED
|
360
|
367
|
|
Treatment Phase (Overall Study)
NOT COMPLETED
|
79
|
72
|
Reasons for withdrawal
| Measure |
Patiromer
Randomized participants who received a daily dose of patiromer, with possible dose adjustments based on subsequent local serum potassium level, during the Treatment Phase.
The starting dose of patiromer was 1 packet/day taken either with food or without food. Based upon the K+ management algorithms, patiromer was to be increased by 1 packet per day in intervals of at least 1 week (±3 days). If hypokalemia developed during the Treatment Phase, then the study drug was to be down titrated (lowest acceptable dose was 0 packets/day) until local serum K+ ≥4.0 mEq/l. Doses of patiromer were 0 packets/day, 1 packet/day, 2 packets/day, and 3 packets/day (maximum dose).
mEq/l = Milliequivalents Per Liter
|
Placebo
Randomized participants who received a daily dose of placebo, with possible dose adjustments based on subsequent local serum potassium level, during the Treatment Phase.
The starting dose of placebo was 1 packet/day taken either with food or without food. Based upon the K+ management algorithms, placebo was to be increased by 1 packet per day in intervals of at least 1 week (±3 days). If hypokalemia developed during the Treatment Phase, then the study drug was to be down-titrated (lowest acceptable dose was 0 packets/day) until local serum K+ ≥4.0 mEq/l. Doses of placebo were 0 packets/day, 1 packet/day, 2 packets/day, and 3 packets/day (maximum dose).
mEq/l = Milliequivalents Per Liter
|
|---|---|---|
|
Run-in Phase
Randomization Criterion #1
|
24
|
0
|
|
Run-in Phase
Randomization Criteria #1, #2
|
5
|
0
|
|
Run-in Phase
Randomization Criteria #1, #2 #4; AE; 1 Wk After 3 Patiromer Packets/Day, sK+ >5.0 Meq/L
|
1
|
0
|
|
Run-in Phase
Randomization Criteria #1, #3
|
1
|
0
|
|
Run-in Phase
Randomization Criteria #1, #4
|
1
|
0
|
|
Run-in Phase
Randomization Crit #1, #4; Withdraw By Subject; 1 Wk After 3 Patiromer Packets/Day, sK+ >5.0 Meq/L
|
1
|
0
|
|
Run-in Phase
Randomization Criteria #1, #4; 1 Wk After 3 Patiromer Packets/Day, sK+ >5.0 Meq/L
|
1
|
0
|
|
Run-in Phase
Randomization Criterion #1; AE
|
4
|
0
|
|
Run-in Phase
Randomization Criterion #1; AE; 1 Wk After 3 Patiromer Packets/Day, sK+ >5.0 Meq/L
|
1
|
0
|
|
Run-in Phase
Randomization Criterion #1; 1 Wk After 3 Patiromer Packets/Day, sK+ >5.0 Meq/L
|
2
|
0
|
|
Run-in Phase
Randomization Criterion #2
|
5
|
0
|
|
Run-in Phase
Randomization Criteria #2, #3
|
1
|
0
|
|
Run-in Phase
Randomization Criteria #2, #3, #4
|
1
|
0
|
|
Run-in Phase
Randomization Criteria #2, #4
|
4
|
0
|
|
Run-in Phase
Randomization Criterion #3
|
11
|
0
|
|
Run-in Phase
Randomization Criteria #3, #4
|
1
|
0
|
|
Run-in Phase
Randomization Criteria #3, #4; 2 Wks After Taking Min 0 Packet/Day, sK+ Is < 4.0 Meq/L
|
2
|
0
|
|
Run-in Phase
Randomization Criterion #3; 1 Wk After 3 Patiromer Packets/Day, sK+ >5.0 Meq/L
|
1
|
0
|
|
Run-in Phase
Randomization Criterion #4
|
3
|
0
|
|
Run-in Phase
Randomization Criterion #3; Physician Decision
|
1
|
0
|
|
Run-in Phase
Randomization Criterion #4; AE
|
4
|
0
|
|
Run-in Phase
Randomization Criterion #4; AE; 2 Wks After Taking Min 0 Packet/Day, sK+ Is < 4.0 Meq/L
|
1
|
0
|
|
Run-in Phase
Randomization Criterion #3; Exceeded 12 Weeks Of Run In
|
1
|
0
|
|
Run-in Phase
Randomization Criterion #4; 1 Wk After 3 Patiromer Packets/Day, sK+ >5.0 Meq/L
|
2
|
0
|
|
Run-in Phase
Randomization Criterion #4; 2 Wks After Taking Min 0 Packet/Day, sK+ Is < 4.0 Meq/L
|
1
|
0
|
|
Run-in Phase
AE (Adverse Event)
|
17
|
0
|
|
Run-in Phase
AE; Withdrawal By Subject
|
3
|
0
|
|
Run-in Phase
AE; Withdrawal By Subject; 1 Wk After 3 Patiromer Packets/Day, sK+ >5.0 Meq/L
|
1
|
0
|
|
Run-in Phase
AE; 1 Wk After 3 Patiromer Packets/Day, sK+ >5.0 Meq/L
|
1
|
0
|
|
Run-in Phase
AE; 2 Wks After Taking Min 0 Packet/Day, sK+ Is < 4.0 Meq/L
|
2
|
0
|
|
Run-in Phase
Withdrawal by Subject
|
43
|
0
|
|
Run-in Phase
AE; Physician Decision
|
1
|
0
|
|
Run-in Phase
1 Wk After 3 Patiromer Packets/Day, sK+ >5.0 Meq/L
|
10
|
0
|
|
Run-in Phase
Withdrawal By Subject; Withdrawal Of Consent
|
1
|
0
|
|
Run-in Phase
2 Wks After Taking Min 0 Packet/Day, sK+ Is < 4.0 Meq/L
|
6
|
0
|
|
Run-in Phase
Death
|
1
|
0
|
|
Run-in Phase
Non-Compliance With Study Drug
|
2
|
0
|
|
Run-in Phase
Physician Decision
|
1
|
0
|
|
Run-in Phase
Protocol Violation
|
13
|
0
|
|
Run-in Phase
Sponsor Request
|
34
|
0
|
|
Run-in Phase
Study Terminated By Sponsor
|
71
|
0
|
|
Run-in Phase
Withdrawal Of Consent
|
1
|
0
|
|
Run-in Phase
Exceeded 12 Weeks Of Run In
|
2
|
0
|
|
Run-in Phase
Not treated with Patiromer during Run-in
|
27
|
0
|
|
Treatment Phase (Overall Study)
Protocol Violation
|
0
|
1
|
|
Treatment Phase (Overall Study)
Physician Decision
|
20
|
13
|
|
Treatment Phase (Overall Study)
Adverse Event
|
27
|
21
|
|
Treatment Phase (Overall Study)
Lost to Follow-up
|
1
|
0
|
|
Treatment Phase (Overall Study)
Consent withdrawn by subject
|
21
|
25
|
|
Treatment Phase (Overall Study)
End of study visit not completed/delayed
|
1
|
3
|
|
Treatment Phase (Overall Study)
Early study termination
|
0
|
1
|
|
Treatment Phase (Overall Study)
Treatment discontinuation
|
2
|
2
|
|
Treatment Phase (Overall Study)
Delayed visit and insufficient study
|
6
|
6
|
|
Treatment Phase (Overall Study)
Sponsor's decision
|
1
|
0
|
Baseline Characteristics
Patiromer for the Management of Hyperkalemia in Subjects Receiving RAASi Medications for the Treatment of Heart Failure (DIAMOND)
Baseline characteristics by cohort
| Measure |
Patiromer
n=439 Participants
Randomized participants who received a daily dose of patiromer, with possible dose adjustments based on subsequent local serum potassium level, during the Treatment Phase.
The starting dose of patiromer was 1 packet/day taken either with food or without food. Based upon the K+ management algorithms, patiromer was to be increased by 1 packet per day in intervals of at least 1 week (±3 days). If hypokalemia developed during the Treatment Phase, then the study drug was to be down titrated (lowest acceptable dose was 0 packets/day) until local serum K+ ≥4.0 mEq/l. Doses of patiromer were 0 packets/day, 1 packet/day, 2 packets/day, and 3 packets/day (maximum dose).
|
Placebo
n=439 Participants
Randomized participants who received a daily dose of placebo, with possible dose adjustments based on subsequent local serum potassium level, during the Treatment Phase.
The starting dose of placebo was 1 packet/day taken either with food or without food. Based upon the K+ management algorithms, placebo was to be increased by 1 packet per day in intervals of at least 1 week (±3 days). If hypokalemia developed during the Treatment Phase, then the study drug was to be down-titrated (lowest acceptable dose was 0 packets/day) until local serum K+ ≥4.0 mEq/l. Doses of placebo were 0 packets/day, 1 packet/day, 2 packets/day, and 3 packets/day (maximum dose).
|
Total
n=878 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
181 Participants
n=5 Participants
|
169 Participants
n=7 Participants
|
350 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
258 Participants
n=5 Participants
|
270 Participants
n=7 Participants
|
528 Participants
n=5 Participants
|
|
Age, Continuous
|
66.6 years
STANDARD_DEVIATION 10.0 • n=5 Participants
|
67.1 years
STANDARD_DEVIATION 9.9 • n=7 Participants
|
66.9 years
STANDARD_DEVIATION 10.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
112 Participants
n=5 Participants
|
126 Participants
n=7 Participants
|
238 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
327 Participants
n=5 Participants
|
313 Participants
n=7 Participants
|
640 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
56 Participants
n=5 Participants
|
57 Participants
n=7 Participants
|
113 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
381 Participants
n=5 Participants
|
379 Participants
n=7 Participants
|
760 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Region of Enrollment
Argentina
|
16 participants
n=5 Participants
|
16 participants
n=7 Participants
|
32 participants
n=5 Participants
|
|
Region of Enrollment
Belgium
|
0 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Region of Enrollment
Brazil
|
6 participants
n=5 Participants
|
10 participants
n=7 Participants
|
16 participants
n=5 Participants
|
|
Region of Enrollment
Bulgaria
|
43 participants
n=5 Participants
|
48 participants
n=7 Participants
|
91 participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Region of Enrollment
Czechia
|
2 participants
n=5 Participants
|
7 participants
n=7 Participants
|
9 participants
n=5 Participants
|
|
Region of Enrollment
France
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Region of Enrollment
Georgia
|
139 participants
n=5 Participants
|
118 participants
n=7 Participants
|
257 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
4 participants
n=5 Participants
|
2 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Region of Enrollment
Hungary
|
8 participants
n=5 Participants
|
11 participants
n=7 Participants
|
19 participants
n=5 Participants
|
|
Region of Enrollment
Israel
|
8 participants
n=5 Participants
|
4 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
3 participants
n=5 Participants
|
4 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
Region of Enrollment
Mexico
|
6 participants
n=5 Participants
|
4 participants
n=7 Participants
|
10 participants
n=5 Participants
|
|
Region of Enrollment
Netherlands
|
3 participants
n=5 Participants
|
1 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
37 participants
n=5 Participants
|
43 participants
n=7 Participants
|
80 participants
n=5 Participants
|
|
Region of Enrollment
Russia
|
37 participants
n=5 Participants
|
42 participants
n=7 Participants
|
79 participants
n=5 Participants
|
|
Region of Enrollment
Serbia
|
3 participants
n=5 Participants
|
5 participants
n=7 Participants
|
8 participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
11 participants
n=5 Participants
|
14 participants
n=7 Participants
|
25 participants
n=5 Participants
|
|
Region of Enrollment
Ukraine
|
81 participants
n=5 Participants
|
75 participants
n=7 Participants
|
156 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
30 participants
n=5 Participants
|
32 participants
n=7 Participants
|
62 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for PlaceboAdjusted mean changes in serum K+ from Baseline.
Outcome measures
| Measure |
Patiromer
n=439 Participants
Randomized participants who received a daily dose of patiromer, with possible dose adjustments based on subsequent local serum potassium level, during the Treatment Phase.
The starting dose of patiromer was 1 packet/day taken either with food or without food. Based upon the K+ management algorithms, patiromer was to be increased by 1 packet per day in intervals of at least 1 week (±3 days). If hypokalemia developed during the Treatment Phase, then the study drug was to be down titrated (lowest acceptable dose was 0 packets/day) until local serum K+ ≥4.0 mEq/l. Doses of patiromer were 0 packets/day, 1 packet/day, 2 packets/day, and 3 packets/day (maximum dose).
|
Placebo
n=439 Participants
Randomized participants who received a daily dose of placebo, with possible dose adjustments based on subsequent local serum potassium level, during the Treatment Phase.
The starting dose of placebo was 1 packet/day taken either with food or without food. Based upon the K+ management algorithms, placebo was to be increased by 1 packet per day in intervals of at least 1 week (±3 days). If hypokalemia developed during the Treatment Phase, then the study drug was to be down-titrated (lowest acceptable dose was 0 packets/day) until local serum K+ ≥4.0 mEq/l. Doses of placebo were 0 packets/day, 1 packet/day, 2 packets/day, and 3 packets/day (maximum dose).
|
|---|---|---|
|
Changes in Serum K+ Levels From Baseline
|
0.029 Milliequivalents Per Liter (mEq/l)
Standard Error 0.019
|
0.127 Milliequivalents Per Liter (mEq/l)
Standard Error 0.019
|
SECONDARY outcome
Timeframe: From Day 1/Baseline to week 90Cumulative incidence of the first event of hyperkalemia with a serum K+ value \>5.5 mEq/l taking death as competing and calculated as CIF Estimates (95% CI) over time. Aalen-Johansen estimators of the cumulative incidence function with death as a competing event. CIF = cumulative incidence function; mEq/l = Milliequivalents Per Liter
Outcome measures
| Measure |
Patiromer
n=439 Participants
Randomized participants who received a daily dose of patiromer, with possible dose adjustments based on subsequent local serum potassium level, during the Treatment Phase.
The starting dose of patiromer was 1 packet/day taken either with food or without food. Based upon the K+ management algorithms, patiromer was to be increased by 1 packet per day in intervals of at least 1 week (±3 days). If hypokalemia developed during the Treatment Phase, then the study drug was to be down titrated (lowest acceptable dose was 0 packets/day) until local serum K+ ≥4.0 mEq/l. Doses of patiromer were 0 packets/day, 1 packet/day, 2 packets/day, and 3 packets/day (maximum dose).
|
Placebo
n=439 Participants
Randomized participants who received a daily dose of placebo, with possible dose adjustments based on subsequent local serum potassium level, during the Treatment Phase.
The starting dose of placebo was 1 packet/day taken either with food or without food. Based upon the K+ management algorithms, placebo was to be increased by 1 packet per day in intervals of at least 1 week (±3 days). If hypokalemia developed during the Treatment Phase, then the study drug was to be down-titrated (lowest acceptable dose was 0 packets/day) until local serum K+ ≥4.0 mEq/l. Doses of placebo were 0 packets/day, 1 packet/day, 2 packets/day, and 3 packets/day (maximum dose).
|
|---|---|---|
|
CIF Estimates of the Time to First Hyperkalemia Event With Serum K+ Level > 5.5 mEq/l Over Time
Week 78
|
0.30 Probability
Interval 0.22 to 0.4
|
0.34 Probability
Interval 0.26 to 0.42
|
|
CIF Estimates of the Time to First Hyperkalemia Event With Serum K+ Level > 5.5 mEq/l Over Time
Week 1
|
0.02 Probability
Interval 0.01 to 0.04
|
0.04 Probability
Interval 0.03 to 0.06
|
|
CIF Estimates of the Time to First Hyperkalemia Event With Serum K+ Level > 5.5 mEq/l Over Time
Week 2
|
0.04 Probability
Interval 0.02 to 0.06
|
0.08 Probability
Interval 0.06 to 0.11
|
|
CIF Estimates of the Time to First Hyperkalemia Event With Serum K+ Level > 5.5 mEq/l Over Time
Week 6
|
0.05 Probability
Interval 0.03 to 0.07
|
0.10 Probability
Interval 0.08 to 0.13
|
|
CIF Estimates of the Time to First Hyperkalemia Event With Serum K+ Level > 5.5 mEq/l Over Time
Week 18
|
0.08 Probability
Interval 0.06 to 0.12
|
0.14 Probability
Interval 0.11 to 0.18
|
|
CIF Estimates of the Time to First Hyperkalemia Event With Serum K+ Level > 5.5 mEq/l Over Time
Week 30
|
0.13 Probability
Interval 0.1 to 0.17
|
0.20 Probability
Interval 0.15 to 0.24
|
|
CIF Estimates of the Time to First Hyperkalemia Event With Serum K+ Level > 5.5 mEq/l Over Time
Week 42
|
0.17 Probability
Interval 0.12 to 0.22
|
0.24 Probability
Interval 0.19 to 0.29
|
|
CIF Estimates of the Time to First Hyperkalemia Event With Serum K+ Level > 5.5 mEq/l Over Time
Week 54
|
0.21 Probability
Interval 0.15 to 0.27
|
0.29 Probability
Interval 0.23 to 0.35
|
|
CIF Estimates of the Time to First Hyperkalemia Event With Serum K+ Level > 5.5 mEq/l Over Time
Week 66
|
0.25 Probability
Interval 0.18 to 0.32
|
0.34 Probability
Interval 0.26 to 0.42
|
|
CIF Estimates of the Time to First Hyperkalemia Event With Serum K+ Level > 5.5 mEq/l Over Time
Week 90
|
0.34 Probability
Interval 0.23 to 0.44
|
0.34 Probability
Interval 0.26 to 0.42
|
SECONDARY outcome
Timeframe: From Day 1/Baseline to week 102Cumulative incidence of the reduction of the MRA dose below target dose calculated as CIF Estimates (95% CI) over time. Note: The reduction below the MRA target dose must last for at least 14 days (orless if at the end of study) to confirm this endpoint. CIF = cumulative incidence function; mEq/l = Milliequivalents Per Liter
Outcome measures
| Measure |
Patiromer
n=439 Participants
Randomized participants who received a daily dose of patiromer, with possible dose adjustments based on subsequent local serum potassium level, during the Treatment Phase.
The starting dose of patiromer was 1 packet/day taken either with food or without food. Based upon the K+ management algorithms, patiromer was to be increased by 1 packet per day in intervals of at least 1 week (±3 days). If hypokalemia developed during the Treatment Phase, then the study drug was to be down titrated (lowest acceptable dose was 0 packets/day) until local serum K+ ≥4.0 mEq/l. Doses of patiromer were 0 packets/day, 1 packet/day, 2 packets/day, and 3 packets/day (maximum dose).
|
Placebo
n=439 Participants
Randomized participants who received a daily dose of placebo, with possible dose adjustments based on subsequent local serum potassium level, during the Treatment Phase.
The starting dose of placebo was 1 packet/day taken either with food or without food. Based upon the K+ management algorithms, placebo was to be increased by 1 packet per day in intervals of at least 1 week (±3 days). If hypokalemia developed during the Treatment Phase, then the study drug was to be down-titrated (lowest acceptable dose was 0 packets/day) until local serum K+ ≥4.0 mEq/l. Doses of placebo were 0 packets/day, 1 packet/day, 2 packets/day, and 3 packets/day (maximum dose).
|
|---|---|---|
|
CIF Estimates of the Reduction of the MRA Dose Below Target Dose Over Time
Week 18
|
0.10 Probability
Interval 0.08 to 0.14
|
0.15 Probability
Interval 0.12 to 0.19
|
|
CIF Estimates of the Reduction of the MRA Dose Below Target Dose Over Time
Week 30
|
0.14 Probability
Interval 0.1 to 0.18
|
0.19 Probability
Interval 0.15 to 0.23
|
|
CIF Estimates of the Reduction of the MRA Dose Below Target Dose Over Time
Week 1
|
0.02 Probability
Interval 0.01 to 0.04
|
0.04 Probability
Interval 0.03 to 0.07
|
|
CIF Estimates of the Reduction of the MRA Dose Below Target Dose Over Time
Week 2
|
0.03 Probability
Interval 0.02 to 0.05
|
0.08 Probability
Interval 0.06 to 0.11
|
|
CIF Estimates of the Reduction of the MRA Dose Below Target Dose Over Time
Week 6
|
0.06 Probability
Interval 0.04 to 0.08
|
0.12 Probability
Interval 0.09 to 0.15
|
|
CIF Estimates of the Reduction of the MRA Dose Below Target Dose Over Time
Week 42
|
0.16 Probability
Interval 0.12 to 0.21
|
0.23 Probability
Interval 0.18 to 0.28
|
|
CIF Estimates of the Reduction of the MRA Dose Below Target Dose Over Time
Week 54
|
0.19 Probability
Interval 0.14 to 0.24
|
0.26 Probability
Interval 0.2 to 0.32
|
|
CIF Estimates of the Reduction of the MRA Dose Below Target Dose Over Time
Week 66
|
0.22 Probability
Interval 0.16 to 0.29
|
0.27 Probability
Interval 0.21 to 0.33
|
|
CIF Estimates of the Reduction of the MRA Dose Below Target Dose Over Time
Week 78
|
0.27 Probability
Interval 0.2 to 0.35
|
0.29 Probability
Interval 0.22 to 0.36
|
|
CIF Estimates of the Reduction of the MRA Dose Below Target Dose Over Time
Week 90
|
0.27 Probability
Interval 0.2 to 0.35
|
0.29 Probability
Interval 0.22 to 0.36
|
|
CIF Estimates of the Reduction of the MRA Dose Below Target Dose Over Time
Week 102
|
0.27 Probability
Interval 0.2 to 0.35
|
NA Probability
Interval 0.0 to 0.0
Not feasible to estimate the cumulative incidence at a time beyond the largest observed time
|
SECONDARY outcome
Timeframe: Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for PlaceboParticipant's follow-up is from the date of the first dose of randomized study medication up to the participant's end of study date or 24 Jun 2021, whichever comes first. Annualized event rate per 100 subject-years= The total number of events for all subjects in the treatment group divided by the total subject-years of follow-up in that treatment group multiplied by 100.
Outcome measures
| Measure |
Patiromer
n=439 Participants
Randomized participants who received a daily dose of patiromer, with possible dose adjustments based on subsequent local serum potassium level, during the Treatment Phase.
The starting dose of patiromer was 1 packet/day taken either with food or without food. Based upon the K+ management algorithms, patiromer was to be increased by 1 packet per day in intervals of at least 1 week (±3 days). If hypokalemia developed during the Treatment Phase, then the study drug was to be down titrated (lowest acceptable dose was 0 packets/day) until local serum K+ ≥4.0 mEq/l. Doses of patiromer were 0 packets/day, 1 packet/day, 2 packets/day, and 3 packets/day (maximum dose).
|
Placebo
n=439 Participants
Randomized participants who received a daily dose of placebo, with possible dose adjustments based on subsequent local serum potassium level, during the Treatment Phase.
The starting dose of placebo was 1 packet/day taken either with food or without food. Based upon the K+ management algorithms, placebo was to be increased by 1 packet per day in intervals of at least 1 week (±3 days). If hypokalemia developed during the Treatment Phase, then the study drug was to be down-titrated (lowest acceptable dose was 0 packets/day) until local serum K+ ≥4.0 mEq/l. Doses of placebo were 0 packets/day, 1 packet/day, 2 packets/day, and 3 packets/day (maximum dose).
|
|---|---|---|
|
Investigator-reported Events of Hyperkalemia
|
82.38 Ann. event rate per 100 subject-years
|
114.65 Ann. event rate per 100 subject-years
|
SECONDARY outcome
Timeframe: Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for PlaceboAnalyzed using Win Ratio approach with the following hierarchical components: 1. Time to CV death 2. Total number of CV hospitalizations 3. Total number of hyperkalemia toxicity events with serum K+ \>6.5 mEq/l 4. Total number of hyperkalemia events with serum K+ \>6.0-6.5 mEq/l 5. Total number of hyperkalemia events with serum K+ \>5.0 mEq/l MHTE=More hyperkalemia toxicity events; MHE=More hyperkalemia events; CV=Cardiovascular
Outcome measures
| Measure |
Patiromer
n=878 Participants
Randomized participants who received a daily dose of patiromer, with possible dose adjustments based on subsequent local serum potassium level, during the Treatment Phase.
The starting dose of patiromer was 1 packet/day taken either with food or without food. Based upon the K+ management algorithms, patiromer was to be increased by 1 packet per day in intervals of at least 1 week (±3 days). If hypokalemia developed during the Treatment Phase, then the study drug was to be down titrated (lowest acceptable dose was 0 packets/day) until local serum K+ ≥4.0 mEq/l. Doses of patiromer were 0 packets/day, 1 packet/day, 2 packets/day, and 3 packets/day (maximum dose).
|
Placebo
Randomized participants who received a daily dose of placebo, with possible dose adjustments based on subsequent local serum potassium level, during the Treatment Phase.
The starting dose of placebo was 1 packet/day taken either with food or without food. Based upon the K+ management algorithms, placebo was to be increased by 1 packet per day in intervals of at least 1 week (±3 days). If hypokalemia developed during the Treatment Phase, then the study drug was to be down-titrated (lowest acceptable dose was 0 packets/day) until local serum K+ ≥4.0 mEq/l. Doses of placebo were 0 packets/day, 1 packet/day, 2 packets/day, and 3 packets/day (maximum dose).
|
|---|---|---|
|
Hyperkalemia-related Hard Outcomes Endpoints
More CV hospitalizations in Patiromer Group
|
4178 Events
|
—
|
|
Hyperkalemia-related Hard Outcomes Endpoints
MHTE with serum K+>6.5 in Patiromer Group
|
401 Events
|
—
|
|
Hyperkalemia-related Hard Outcomes Endpoints
MHE with serum K+>6.0-6.5 in Placebo Group
|
4283 Events
|
—
|
|
Hyperkalemia-related Hard Outcomes Endpoints
MHE with serum K+>6.0-6.5 in Patiromer Group
|
1446 Events
|
—
|
|
Hyperkalemia-related Hard Outcomes Endpoints
MHE with serum K+>5.0-6.0 in Placebo Group
|
55633 Events
|
—
|
|
Hyperkalemia-related Hard Outcomes Endpoints
CV death in Placebo Group First
|
3491 Events
|
—
|
|
Hyperkalemia-related Hard Outcomes Endpoints
CV death in Patiromer Group First
|
4609 Events
|
—
|
|
Hyperkalemia-related Hard Outcomes Endpoints
More CV hospitalizations in Placebo Group
|
4539 Events
|
—
|
|
Hyperkalemia-related Hard Outcomes Endpoints
MHTE with serum K+>6.5 in Placebo Group
|
419 Events
|
—
|
|
Hyperkalemia-related Hard Outcomes Endpoints
MHE with serum K+>5.0-6.0 in Patiromer Group
|
34156 Events
|
—
|
|
Hyperkalemia-related Hard Outcomes Endpoints
None of the above
|
79566 Events
|
—
|
|
Hyperkalemia-related Hard Outcomes Endpoints
Total number of pairs
|
192721 Events
|
—
|
SECONDARY outcome
Timeframe: Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for PlaceboRAASi use score (0 to 8 points) analyzed using the Win Ratio approach for each pair of participants with the following additive components: 1. All-cause death 2. Occurrence of a CV hospitalization 3. HF medication use and dose for i) an ACEi/ARB/ARNi, ii) a MRA, and iii) a beta-blocker Each participant in each comparison can have 0-8 points and all participants are compared using this score at the respective appropriate follow-up time point. RAASi=renin-angiotensin-aldosterone system inhibitor; ACEi=angiotensin converting enzyme inhibitor; ARB=angiotensin receptor blocker; ARNi=angiotensin receptor/neprilysin inhibitor; MRA=mineralocorticoid receptor antagonist.
Outcome measures
| Measure |
Patiromer
n=878 Participants
Randomized participants who received a daily dose of patiromer, with possible dose adjustments based on subsequent local serum potassium level, during the Treatment Phase.
The starting dose of patiromer was 1 packet/day taken either with food or without food. Based upon the K+ management algorithms, patiromer was to be increased by 1 packet per day in intervals of at least 1 week (±3 days). If hypokalemia developed during the Treatment Phase, then the study drug was to be down titrated (lowest acceptable dose was 0 packets/day) until local serum K+ ≥4.0 mEq/l. Doses of patiromer were 0 packets/day, 1 packet/day, 2 packets/day, and 3 packets/day (maximum dose).
|
Placebo
Randomized participants who received a daily dose of placebo, with possible dose adjustments based on subsequent local serum potassium level, during the Treatment Phase.
The starting dose of placebo was 1 packet/day taken either with food or without food. Based upon the K+ management algorithms, placebo was to be increased by 1 packet per day in intervals of at least 1 week (±3 days). If hypokalemia developed during the Treatment Phase, then the study drug was to be down-titrated (lowest acceptable dose was 0 packets/day) until local serum K+ ≥4.0 mEq/l. Doses of placebo were 0 packets/day, 1 packet/day, 2 packets/day, and 3 packets/day (maximum dose).
|
|---|---|---|
|
RAASi Use Score
Number of wins in Patiromer Group
|
62073 Events
|
—
|
|
RAASi Use Score
Number of wins in Placebo Group
|
49733 Events
|
—
|
|
RAASi Use Score
Number of ties
|
80915 Events
|
—
|
|
RAASi Use Score
Total number of pairs
|
192721 Events
|
—
|
Adverse Events
Patiromer
Serious events: 54 serious events
Other events: 320 other events
Deaths: 24 deaths
Placebo
Serious events: 58 serious events
Other events: 325 other events
Deaths: 18 deaths
Serious adverse events
| Measure |
Patiromer
n=439 participants at risk
Randomized participants who received a daily dose of patiromer, with possible dose adjustments based on subsequent local serum potassium level, during the Treatment Phase.
The starting dose of patiromer was 1 packet/day taken either with food or without food. Based upon the K+ management algorithms, patiromer was to be increased by 1 packet per day in intervals of at least 1 week (±3 days). If hypokalemia developed during the Treatment Phase, then the study drug was to be down titrated (lowest acceptable dose was 0 packets/day) until local serum K+ ≥4.0 mEq/l. Doses of patiromer were 0 packets/day, 1 packet/day, 2 packets/day, and 3 packets/day (maximum dose).
|
Placebo
n=439 participants at risk
Randomized participants who received a daily dose of placebo, with possible dose adjustments based on subsequent local serum potassium level, during the Treatment Phase.
The starting dose of placebo was 1 packet/day taken either with food or without food. Based upon the K+ management algorithms, placebo was to be increased by 1 packet per day in intervals of at least 1 week (±3 days). If hypokalemia developed during the Treatment Phase, then the study drug was to be down-titrated (lowest acceptable dose was 0 packets/day) until local serum K+ ≥4.0 mEq/l. Doses of placebo were 0 packets/day, 1 packet/day, 2 packets/day, and 3 packets/day (maximum dose).
|
|---|---|---|
|
Vascular disorders
Peripheral ischaemia
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Vascular disorders
Hypotension
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.46%
2/439 • Number of events 2 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancoast's tumour
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Plasmacytoma
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid neoplasm
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
General disorders
Sudden death
|
2.3%
10/439 • Number of events 10 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
2.3%
10/439 • Number of events 10 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
General disorders
Death
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Injury, poisoning and procedural complications
Traumatic intracranial haemorrhage
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Injury, poisoning and procedural complications
Vascular procedure complication
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Investigations
Ultrasound pancreas abnormal
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Cardiac disorders
Cardiac failure
|
2.1%
9/439 • Number of events 10 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
3.4%
15/439 • Number of events 18 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Cardiac disorders
Angina unstable
|
0.68%
3/439 • Number of events 3 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.68%
3/439 • Number of events 3 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Cardiac disorders
Acute left ventricular failure
|
0.46%
2/439 • Number of events 2 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Cardiac disorders
Atrial fibrillation
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.46%
2/439 • Number of events 2 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Cardiac disorders
Acute coronary syndrome
|
0.23%
1/439 • Number of events 2 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Cardiac disorders
Acute myocardial infarction
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Cardiac disorders
Cardiac failure congestive
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 2 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Cardiac disorders
Ventricular tachycardia
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Cardiac disorders
Angina pectoris
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Cardiac disorders
Left ventricular failure
|
0.23%
1/439 • Number of events 2 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Cardiac disorders
Myocardial infarction
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Cardiac disorders
Myocardial ischaemia
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Cardiac disorders
Ventricular extrasystoles
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Cardiac disorders
Cardiomyopathy
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Cardiac disorders
Pulseless electrical activity
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 2 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Cardiac disorders
Cardiac failure acute
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.91%
4/439 • Number of events 6 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Cardiac disorders
Cardiac failure chronic
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.23%
1/439 • Number of events 2 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory arrest
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Respiratory, thoracic and mediastinal disorders
Vocal cord dysfunction
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.68%
3/439 • Number of events 4 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Nervous system disorders
Ischaemic stroke
|
0.46%
2/439 • Number of events 2 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Nervous system disorders
Cerebral infarction
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Nervous system disorders
Transient ischaemic attack
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Nervous system disorders
Brain injury
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Nervous system disorders
Status epilepticus
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Nervous system disorders
Vascular encephalopathy
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Gastrointestinal disorders
Intestinal pseudo-obstruction
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Gastrointestinal disorders
Vomiting
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Gastrointestinal disorders
Inflammatory bowel disease
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Gastrointestinal disorders
Umbilical hernia
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Renal and urinary disorders
Renal failure
|
0.46%
2/439 • Number of events 2 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Renal and urinary disorders
Acute kidney injury
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Renal and urinary disorders
Calculus urinary
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Renal and urinary disorders
End stage renal disease
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Skin and subcutaneous tissue disorders
Diabetic foot
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Musculoskeletal and connective tissue disorders
Muscle atrophy
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Metabolism and nutrition disorders
Dehydration
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Infections and infestations
Pneumonia
|
1.1%
5/439 • Number of events 5 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
1.4%
6/439 • Number of events 6 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Infections and infestations
COVID-19
|
0.46%
2/439 • Number of events 2 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.68%
3/439 • Number of events 3 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Infections and infestations
COVID-19 pneumonia
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Infections and infestations
Cellulitis
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Infections and infestations
Gangrene
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.46%
2/439 • Number of events 2 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Infections and infestations
Endocarditis
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
Other adverse events
| Measure |
Patiromer
n=439 participants at risk
Randomized participants who received a daily dose of patiromer, with possible dose adjustments based on subsequent local serum potassium level, during the Treatment Phase.
The starting dose of patiromer was 1 packet/day taken either with food or without food. Based upon the K+ management algorithms, patiromer was to be increased by 1 packet per day in intervals of at least 1 week (±3 days). If hypokalemia developed during the Treatment Phase, then the study drug was to be down titrated (lowest acceptable dose was 0 packets/day) until local serum K+ ≥4.0 mEq/l. Doses of patiromer were 0 packets/day, 1 packet/day, 2 packets/day, and 3 packets/day (maximum dose).
|
Placebo
n=439 participants at risk
Randomized participants who received a daily dose of placebo, with possible dose adjustments based on subsequent local serum potassium level, during the Treatment Phase.
The starting dose of placebo was 1 packet/day taken either with food or without food. Based upon the K+ management algorithms, placebo was to be increased by 1 packet per day in intervals of at least 1 week (±3 days). If hypokalemia developed during the Treatment Phase, then the study drug was to be down-titrated (lowest acceptable dose was 0 packets/day) until local serum K+ ≥4.0 mEq/l. Doses of placebo were 0 packets/day, 1 packet/day, 2 packets/day, and 3 packets/day (maximum dose).
|
|---|---|---|
|
Vascular disorders
Hypotension
|
3.4%
15/439 • Number of events 17 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
3.0%
13/439 • Number of events 14 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Vascular disorders
Hypertension
|
1.8%
8/439 • Number of events 8 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.46%
2/439 • Number of events 2 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
General disorders
Asthenia
|
1.1%
5/439 • Number of events 5 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
1.8%
8/439 • Number of events 9 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
General disorders
Oedema peripheral
|
0.46%
2/439 • Number of events 2 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
1.1%
5/439 • Number of events 5 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Reproductive system and breast disorders
Gynaecomastia
|
1.4%
6/439 • Number of events 6 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Investigations
Glomerular filtration rate decreased
|
3.4%
15/439 • Number of events 19 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
2.3%
10/439 • Number of events 14 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Investigations
Blood creatinine increased
|
0.46%
2/439 • Number of events 2 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
1.1%
5/439 • Number of events 5 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Cardiac disorders
Cardiac failure
|
2.3%
10/439 • Number of events 11 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
2.3%
10/439 • Number of events 11 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Cardiac disorders
Atrial fibrillation
|
1.1%
5/439 • Number of events 6 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.68%
3/439 • Number of events 3 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Blood and lymphatic system disorders
Anaemia
|
2.5%
11/439 • Number of events 11 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
1.1%
5/439 • Number of events 6 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
2.1%
9/439 • Number of events 9 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
1.6%
7/439 • Number of events 7 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Respiratory, thoracic and mediastinal disorders
Hydrothorax
|
1.4%
6/439 • Number of events 7 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.46%
2/439 • Number of events 2 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
1.1%
5/439 • Number of events 6 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.91%
4/439 • Number of events 4 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
1.1%
5/439 • Number of events 7 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Nervous system disorders
Headache
|
2.1%
9/439 • Number of events 9 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
2.5%
11/439 • Number of events 14 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Gastrointestinal disorders
Diarrhoea
|
4.3%
19/439 • Number of events 20 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
3.4%
15/439 • Number of events 15 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Gastrointestinal disorders
Constipation
|
2.5%
11/439 • Number of events 13 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
1.1%
5/439 • Number of events 5 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.46%
2/439 • Number of events 2 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
1.1%
5/439 • Number of events 5 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Renal and urinary disorders
Chronic kidney disease
|
1.1%
5/439 • Number of events 7 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
1.8%
8/439 • Number of events 8 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Renal and urinary disorders
Renal impairment
|
1.1%
5/439 • Number of events 5 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
1.6%
7/439 • Number of events 7 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.3%
10/439 • Number of events 11 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
1.4%
6/439 • Number of events 6 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
1.4%
6/439 • Number of events 6 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.68%
3/439 • Number of events 3 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
44.9%
197/439 • Number of events 335 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
54.2%
238/439 • Number of events 412 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
15.0%
66/439 • Number of events 75 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
10.7%
47/439 • Number of events 53 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
4.3%
19/439 • Number of events 20 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
5.0%
22/439 • Number of events 25 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
2.3%
10/439 • Number of events 11 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.68%
3/439 • Number of events 3 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
1.6%
7/439 • Number of events 7 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
1.1%
5/439 • Number of events 5 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Metabolism and nutrition disorders
Iron deficiency
|
1.4%
6/439 • Number of events 6 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.46%
2/439 • Number of events 2 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
1.1%
5/439 • Number of events 5 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Infections and infestations
Pneumonia
|
1.6%
7/439 • Number of events 8 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
0.23%
1/439 • Number of events 1 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Infections and infestations
COVID-19
|
1.4%
6/439 • Number of events 6 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
1.4%
6/439 • Number of events 8 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
|
Infections and infestations
Respiratory tract infection viral
|
0.00%
0/439 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
1.4%
6/439 • Number of events 6 • Mean duration of exposure: 227.9 days for Patiromer and 234.5 days for Placebo
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER