NCT03071263: AMBER

Spironolactone With Patiromer in the Treatment of Resistant Hypertension in Chronic Kidney Disease

Completed Phase 2 Results posted Last updated 12 May 2021

What this trial tests

Phase 2 trial testing Patiromer in Hyperkalemia in 295 participants. Completed in 27 November 2018.

Timeline

23 January 2017

Primary endpoint
27 November 2018

27 November 2018

Quick facts

Lead sponsor	Relypsa, Inc.
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	295
Start date	23 January 2017
Primary completion	27 November 2018
Estimated completion	27 November 2018
Sites	40 locations across Georgia, South Africa, Ukraine, United Kingdom, Germany, Hungary, Bulgaria, Croatia

Drugs / interventions tested

• Patiromer — full drug profile →
• Placebo
• Spironolactone (spironolactone) — full drug profile →

Conditions studied

• Hyperkalemia — all drugs for Hyperkalemia →
• Resistant Hypertension — all drugs for Resistant Hypertension →

Sponsor

Relypsa, Inc.

Who can join

18 and older, any sex, with Hyperkalemia or Resistant Hypertension. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Remaining on Spironolactone at Week 12 Primary · At week 12

The proportion of subjects remaining on spironolactone at Week 12 will be compared between treatment groups (spironolactone/patiromer versus spironolactone/placebo). Subjects who discontinued from the study early or discontinued study spironolactone prior to Week 12, for any reason, were considered as not having remained on spironolactone until Week 12.

Group	Value	95% CI
Group 1 - Patiromer	126
Group 2 - Placebo	98

Change in AOBP SBP From Baseline to Week 12 or Last Available AOBP SBP Prior to Addition of Any New BP Medications or Increase From Any Baseline BP Medications Secondary · From baseline to Week 12

AOBP: Automated Office Blood Pressure SBP: Systolic Blood Pressure BP: Blood Pressure

Group	Value	95% CI
Group 1 - Patiromer	-11.3	± 14.11
Group 2 - Placebo	-11.0	± 15.34

Change in AOBP SBP From Baseline to Week 12 Regardless of Increase in Antihypertensives Secondary · From baseline to Week 12

AOBP SBP: Automated Office Systolic Blood Pressure

Group	Value	95% CI
Group 1 - Patiromer	-11.3	± 14.11
Group 2 - Placebo	-11.2	± 15.04

Central Serum Potassium Change From Baseline to Week 12 by Baseline Serum Potassium Category Secondary · From baseline to Week 12

The two baseline potassium subgroups, 4.3-\<4.7 mEq/L versus 4.7-5.1 mEq/L, are based on central laboratory data. If a participant's serum potassium result at baseline was not in one of the two subgroups reported below, the participant's potassium stratum at randomization was used. Therefore, participants with BCSP \<4.3 mEq/L or \>5.1 mEq/L at baseline (Day 0) have been classified according to their serum potassium values at the Screening period.

Baseline Central Serum Potassium 4.3-<4.7 mEq/L

Group	Value	95% CI
Group 1 - Patiromer	0.16	± 0.468
Group 2 - Placebo	0.40	± 0.494

Baseline Central Serum Potassium 4.7-<5.1 mEq/L

Group	Value	95% CI
Group 1 - Patiromer	-0.09	± 0.442
Group 2 - Placebo	0.03	± 0.468

Overall

Group	Value	95% CI
Group 1 - Patiromer	0.02	± 0.469
Group 2 - Placebo	0.20	± 0.514

Participants With Central Serum Potassium <5.5 mEq/L Over Time Secondary · From baseline to Week 12

Baseline Central Serum Potassium: BCSP. The symbols \> and ≤ included in the row titles are used to indicate the time interval \["\>Week1 and ≤Week2" meaning from day 8 until day 14 (included)\]. If a participant's serum potassium result at baseline was not in one of the two subgroups reported below, the participant's potassium stratum at randomization was used. Therefore, participants with BCSP \<4.3 mEq/L or \>5.1 mEq/L at baseline (Day 0) have been classified according to their serum potassium values at the Screening period.

BCSP 4.3-<4.7mEq/L: ≤Week1

Group	Value	95% CI
Group 1 - Patiromer	60
Group 2 - Placebo	62

BCSP 4.3-<4.7mEq/L: >Week1 and ≤Week2

Group	Value	95% CI
Group 1 - Patiromer	57
Group 2 - Placebo	57

BCSP 4.3-<4.7mEq/L: >Week 2 and ≤Week 3

Group	Value	95% CI
Group 1 - Patiromer	59
Group 2 - Placebo	63

BCSP 4.3-<4.7mEq/L: >Week 3 and ≤Week 4

Group	Value	95% CI
Group 1 - Patiromer	61
Group 2 - Placebo	60

BCSP 4.3-<4.7mEq/L: >Week 4 and ≤Week 6

Group	Value	95% CI
Group 1 - Patiromer	61
Group 2 - Placebo	61

BCSP 4.3-<4.7mEq/L: >Week 6 and ≤Week 8

Group	Value	95% CI
Group 1 - Patiromer	61
Group 2 - Placebo	58

BCSP 4.3-<4.7mEq/L: >Week 8 and ≤Week 10

Group	Value	95% CI
Group 1 - Patiromer	58
Group 2 - Placebo	58

BCSP 4.3-<4.7mEq/L: > Week 10 and ≤ Week 12

Group	Value	95% CI
Group 1 - Patiromer	61
Group 2 - Placebo	61

Participants Having Spironolactone Titrations Over Time Secondary · From baseline to Week 12

The titration was performed according to the following criteria: Spironolactone was increased in cases of hypertension, decreased or stopped in cases of hypotension and maintained if the blood pressure results were adequate The symbols \> and ≤ included in the row titles are used to indicate the time interval \["\>Week1 and ≤Week2" meaning from day 8 until day 14 (included)\].

Up : ≤Week 1

Group	Value	95% CI
Group 1 - Patiromer	0
Group 2 - Placebo	0

Up : >Week 1 and ≤Week 2

Group	Value	95% CI
Group 1 - Patiromer	0
Group 2 - Placebo	0

Up : >Week 2 and ≤Week 3

Group	Value	95% CI
Group 1 - Patiromer	88
Group 2 - Placebo	77

Up : >Week 3 and ≤Week 4

Group	Value	95% CI
Group 1 - Patiromer	27
Group 2 - Placebo	21

Up : >Week 4 and ≤Week 6

Group	Value	95% CI
Group 1 - Patiromer	10
Group 2 - Placebo	11

Up : >Week 6 and ≤Week 8

Group	Value	95% CI
Group 1 - Patiromer	6
Group 2 - Placebo	6

Up : >Week 8 and ≤Week 10

Group	Value	95% CI
Group 1 - Patiromer	6
Group 2 - Placebo	7

Up : >Week 10 and ≤Week 12

Group	Value	95% CI
Group 1 - Patiromer	1
Group 2 - Placebo	0

Number of Participants by Spironolactone Dose Prescribed at Each Visit Secondary · From baseline to Week 10

QD: Once daily QOD: Once every other day

50 mg QD : Baseline

Group	Value	95% CI
Group 1 - Patiromer	0
Group 2 - Placebo	0

50 mg QD : Week 1

Group	Value	95% CI
Group 1 - Patiromer	0
Group 2 - Placebo	0

50 mg QD : Week 2

Group	Value	95% CI
Group 1 - Patiromer	0
Group 2 - Placebo	0

50 mg QD : Week 3

Group	Value	95% CI
Group 1 - Patiromer	86
Group 2 - Placebo	76

50 mg QD : Week 4

Group	Value	95% CI
Group 1 - Patiromer	105
Group 2 - Placebo	94

50 mg QD : Week 6

Group	Value	95% CI
Group 1 - Patiromer	106
Group 2 - Placebo	96

50 mg QD : Week 8

Group	Value	95% CI
Group 1 - Patiromer	106
Group 2 - Placebo	85

50 mg QD : Week 10

Group	Value	95% CI
Group 1 - Patiromer	106
Group 2 - Placebo	80

Shifts in Selected Laboratory Tests From Baseline to End of Treatment Secondary · From Baseline to End of Treatment, up to 12 weeks.

The end of treatment value is defined as the last non-missing value on or prior to the last spironolactone dose date (from End of Treatment - Case report form) + 3 days LLN=Lower limit of the normal range. ULN=Upper limit of the normal range. EoT=End of Treatment

Magnesium - Baseline Value <LLN : EoT Value<LLN

Group	Value	95% CI
Group 1 - Patiromer	9
Group 2 - Placebo	4

Magnesium - Baseline Value <LLN : EoT Value Normal

Group	Value	95% CI
Group 1 - Patiromer	3
Group 2 - Placebo	8

Magnesium - Baseline Value <LLN : EoT Value >ULN

Group	Value	95% CI
Group 1 - Patiromer	0
Group 2 - Placebo	0

Magnesium - Baseline Value Normal : EoT Value <LLN

Group	Value	95% CI
Group 1 - Patiromer	12
Group 2 - Placebo	7

Magnesium- Baseline Value Normal: EoT Value Normal

Group	Value	95% CI
Group 1 - Patiromer	103
Group 2 - Placebo	109

Magnesium - Baseline Value Normal : EoT Value >ULN

Group	Value	95% CI
Group 1 - Patiromer	6
Group 2 - Placebo	10

Magnesium - Baseline Value >ULN : EoT Value <LLN

Group	Value	95% CI
Group 1 - Patiromer	0
Group 2 - Placebo	0

Magnesium - Baseline Value >ULN : EoT Value Normal

Group	Value	95% CI
Group 1 - Patiromer	10
Group 2 - Placebo	6

Spironolactone Dose Level at End of 12 Weeks of Study Treatment Secondary · 12 Weeks of Study Treatment

Row title: Participants not completing 12W of study treatment: Participants who had not completed 12 weeks of study treatment.

50 mg QD

Group	Value	95% CI
Group 1 - Patiromer	102
Group 2 - Placebo	76

25 mg QD

Group	Value	95% CI
Group 1 - Patiromer	22
Group 2 - Placebo	19

25 mg QOD

Group	Value	95% CI
Group 1 - Patiromer	2
Group 2 - Placebo	3

Participants not completing 12W of study treatment

Group	Value	95% CI
Group 1 - Patiromer	21
Group 2 - Placebo	50

Number of Participants Requiring Additional New Antihypertensive Medications or Increases to Baseline Antihypertensive Medications Secondary · From baseline to Week 12/Early Termination visit

Row Titles: * AM: Antihypertensive Medication(s) * New AM: Participants who required additional new antihypertensive medication(s) * Increases to baseline AM: Participants who required increases to baseline antihypertensive medication(s) * Addition new (or increase) AM: Participants who required addition of new antihypertensive medication(s) and/or increases to baseline antihypertensive medications * At any time during the study: During study * While on study medication: On medication

New AM : At any time during the study

Group	Value	95% CI
Group 1 - Patiromer	0
Group 2 - Placebo	3

New AM : On medication

Group	Value	95% CI
Group 1 - Patiromer	0
Group 2 - Placebo	1

Increases to baseline AM: During study

Group	Value	95% CI
Group 1 - Patiromer	0
Group 2 - Placebo	2

Increases to baseline AM: On medication

Group	Value	95% CI
Group 1 - Patiromer	0
Group 2 - Placebo	1

Addition new (or increases) AM: During study

Group	Value	95% CI
Group 1 - Patiromer	0
Group 2 - Placebo	4

Addition new (or increases) AM : On medication

Group	Value	95% CI
Group 1 - Patiromer	0
Group 2 - Placebo	2

Adverse events — posted to ClinicalTrials.gov

Time frame: During Treatment Period (12 weeks); until Follow-up Visit 2 weeks after the Week 12 Visit (or Early Termination Visit).. Reporting threshold: 5.0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Group 1 - Patiromer

Serious: 1/147 (1%)

Deaths: 0/147

Group 2 - Placebo

Serious: 4/148 (3%)

Deaths: 1/148

Serious adverse events (5 terms)

Reaction	System	Group 1 - Patiromer	Group 2 - Placebo
Renal failure	Renal and urinary disorders	—	—
Renal colic	Renal and urinary disorders	—	—
Aortic rupture	Vascular disorders	—	—
Humerus fracture	Musculoskeletal and connective tissue disorders	—	—
Hypersensitivity	Immune system disorders	—	—

Other adverse events (5 terms — click to expand)

Reaction	System	Group 1 - Patiromer	Group 2 - Placebo
Renal impairment	Renal and urinary disorders	—	—
Hyperkalaemia	Metabolism and nutrition disorders	—	—
Headache	Nervous system disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Hypotension	Vascular disorders	—	—

Most-reported serious reactions: Renal failure, Renal colic, Aortic rupture, Humerus fracture, Hypersensitivity.

Data from ClinicalTrials.gov NCT03071263 adverse events section.

Sponsor's own description

The purpose of this study is to determine if patiromer treatment in chronic kidney disease (CKD) subjects receiving spironolactone for the treatment of resistant hypertension will result in more persistent use of spironolactone through prevention of hyperkalemia and lead to improved blood pressure control compared with treatment with spironolactone alone (placebo).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Patiromer versus placebo to enable spironolactone use in patients with resistant hypertension and chronic kidney disease (AMBER): a phase 2, randomised, double-blind, placebo-controlled trial.
   Agarwal R, Rossignol P, Romero A, Garza D, et al · · 2019 · cited 243× · PMID 31533906 · DOI 10.1016/s0140-6736(19)32135-x
2. A comparative post hoc analysis of finerenone and spironolactone in resistant hypertension in moderate-to-advanced chronic kidney disease.
   Agarwal R, Pitt B, Palmer BF, Kovesdy CP, et al · · 2023 · cited 66× · PMID 36864892 · DOI 10.1093/ckj/sfac234
3. Design and baseline characteristics of the Finerenone, in addition to standard of care, on the progression of kidney disease in patients with Non-Diabetic Chronic Kidney Disease (FIND-CKD) randomized trial.
   Heerspink HJL, Agarwal R, Bakris GL, Cherney DZI, et al · · 2025 · cited 51× · PMID 38858818 · DOI 10.1093/ndt/gfae132
4. Patiromer versus placebo to enable spironolactone use in patients with resistant hypertension and chronic kidney disease (AMBER): results in the pre-specified subgroup with heart failure.
   Rossignol P, Williams B, Mayo MR, Warren S, et al · · 2020 · cited 31× · PMID 32452085 · DOI 10.1002/ejhf.1860
5. Potassium binders for chronic hyperkalaemia in people with chronic kidney disease.
   Natale P, Palmer SC, Ruospo M, Saglimbene VM, et al · · 2020 · cited 30× · PMID 32588430 · DOI 10.1002/14651858.cd013165.pub2
6. Adverse Effects of Aldosterone: Beyond Blood Pressure.
   Brown JM. · · 2024 · cited 25× · PMID 38497438 · DOI 10.1161/jaha.123.030142
7. Patiromer to Enable Spironolactone Use in the Treatment of Patients with Resistant Hypertension and Chronic Kidney Disease: Rationale and Design of the AMBER Study.
   Agarwal R, Rossignol P, Garza D, Mayo MR, et al · · 2018 · cited 19× · PMID 30176673 · DOI 10.1159/000492622
8. Patiromer and Spironolactone in Resistant Hypertension and Advanced CKD: Analysis of the Randomized AMBER Trial.
   Agarwal R, Rossignol P, Budden J, Mayo MR, et al · · 2021 · cited 13× · PMID 35369022 · DOI 10.34067/kid.0006782020