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

Primary Purpose

Hyperkalemia, Resistant Hypertension

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Patiromer
Placebo
Spironolactone
Sponsored by
Relypsa, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hyperkalemia focused on measuring Treatment of Hyperkalemia, Hyperkalemia, Potassium, Chronic Kidney Disease, Hypertension, Resistant Hypertension, Spironolactone

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age ≥ 18 years
  • Taking at least three medications for blood pressure (one a diuretic)
  • Uncontrolled high blood pressure
  • Abnormal kidney function (with-eGFR, a measure of kidney function, of 25 - ≤ 45 mL/min/1.73m2
  • Normal Blood serum Potassium in a specific range (4.3 - 5.1 mEq/L)

Exclusion Criteria:

  • History of untreated known causes of high blood pressure, excluding kidney disease (not CKD)
  • Inability to measure BP
  • Not taking high blood pressure medications as prescribed medications
  • Recent change in renal function (in the past 3 months) which has required hospitalization or dialysis
  • Renal transplant
  • History of cancer within past 12 months
  • Recent cardiovascular event with last 3 months
  • Clinically significant abnormalities of heart rhythm (ventricular arrhythmia or atrial fibrillation with uncontrolled heart rate)
  • Inability to take study medication
  • Alcoholism

Sites / Locations

  • Investigator Site 1012
  • Investigator Site 1023
  • Investigator Site 1022
  • Investigator Site 1402
  • Investiagor Site 2205
  • Investigator Site 2201
  • Investigator Site 2202
  • Investigator Site 2203
  • Investigator Site 3806
  • Investigator Site 3811
  • Investigator Site 3802
  • Investigator Site 3801
  • Investigator Site 3804
  • Investigator Site 3805
  • Investigator Site 3807
  • Investigator Site 3808
  • Investigator Site 3810
  • Investigator Site 3812
  • Investigator Site 3813
  • Investigator Site 3809
  • Investigator Site 4202
  • Investigator Site 4607
  • Investigator Site 4606
  • Investigator Site 4611
  • Investigator Site 4601
  • Investigator Site 4605
  • Investigator Site 4602
  • Investigator Site 4610
  • Investigator Site 4608
  • Investigator Site 7403
  • Investigator Site 7803
  • Investiagor Site 7809
  • Investigator Site 7808
  • Investigator Site 7802
  • Investigator Site 7805
  • Investigator Site 7801
  • Investigator Site 7804
  • Investigator Site 7807
  • Investigator Site 8202
  • Investigator Site 8205

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Group 1 - Patiromer

Group 2 - Placebo

Arm Description

spironolactone + blinded patiromer

spironolactone + blinded placebo

Outcomes

Primary Outcome Measures

Number of Participants Remaining on Spironolactone 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.

Secondary Outcome Measures

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

Full Information

First Posted
March 1, 2017
Last Updated
May 10, 2021
Sponsor
Relypsa, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03071263
Brief Title
Spironolactone With Patiromer in the Treatment of Resistant Hypertension in Chronic Kidney Disease
Acronym
AMBER
Official Title
A Randomized, Double-Blind, Placebo Controlled, Parallel Group Study of Patiromer for the Enablement of Spironolactone Use for Blood Pressure Control in Patients With Resistant Hypertension and Chronic Kidney Disease
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
January 23, 2017 (Actual)
Primary Completion Date
November 27, 2018 (Actual)
Study Completion Date
November 27, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Relypsa, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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).
Detailed Description
Approximately 290 eligible participants with [chronic kidney disease (CKD) on stable doses of medication] will be randomly assigned to receive a patiromer or placebo starting dose of two packets a day, once a day. All eligible participants will undergo a screening/run-in period (up to 4 weeks) to determine eligibility for study entry. Eligible participants will be randomized and treated for 12 weeks (Treatment Period) and followed for 2 weeks after completing the patiromer or placebo treatment. There are 8 planned clinic visits during the Treatment Period and one planned visit two weeks after the last dose of patiromer or placebo (Follow-up Period). The dose of patiromer or placebo may be increased or decreased (titrated) based on participants' individual potassium response.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperkalemia, Resistant Hypertension
Keywords
Treatment of Hyperkalemia, Hyperkalemia, Potassium, Chronic Kidney Disease, Hypertension, Resistant Hypertension, Spironolactone

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
295 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1 - Patiromer
Arm Type
Experimental
Arm Description
spironolactone + blinded patiromer
Arm Title
Group 2 - Placebo
Arm Type
Experimental
Arm Description
spironolactone + blinded placebo
Intervention Type
Drug
Intervention Name(s)
Patiromer
Other Intervention Name(s)
Veltassa, RLY5016 for Oral Suspension, Patiromer for Oral Suspension
Intervention Description
2 packets/day starting dose, administered orally
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
2 packets/day starting dose, administered orally
Intervention Type
Drug
Intervention Name(s)
Spironolactone
Intervention Description
25 mg tablet/day starting dose, administered orally
Primary Outcome Measure Information:
Title
Number of Participants Remaining on Spironolactone at Week 12
Description
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.
Time Frame
At week 12
Secondary Outcome Measure Information:
Title
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
Description
AOBP: Automated Office Blood Pressure SBP: Systolic Blood Pressure BP: Blood Pressure
Time Frame
From baseline to Week 12
Other Pre-specified Outcome Measures:
Title
Change in AOBP SBP From Baseline to Week 12 Regardless of Increase in Antihypertensives
Description
AOBP SBP: Automated Office Systolic Blood Pressure
Time Frame
From baseline to Week 12
Title
Central Serum Potassium Change From Baseline to Week 12 by Baseline Serum Potassium Category
Description
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.
Time Frame
From baseline to Week 12
Title
Participants With Central Serum Potassium <5.5 mEq/L Over Time
Description
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.
Time Frame
From baseline to Week 12
Title
Participants Having Spironolactone Titrations Over Time
Description
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)].
Time Frame
From baseline to Week 12
Title
Number of Participants by Spironolactone Dose Prescribed at Each Visit
Description
QD: Once daily QOD: Once every other day
Time Frame
From baseline to Week 10
Title
Shifts in Selected Laboratory Tests From Baseline to End of Treatment
Description
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
Time Frame
From Baseline to End of Treatment, up to 12 weeks.
Title
Spironolactone Dose Level at End of 12 Weeks of Study Treatment
Description
Row title: Participants not completing 12W of study treatment: Participants who had not completed 12 weeks of study treatment.
Time Frame
12 Weeks of Study Treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18 years Taking at least three medications for blood pressure (one a diuretic) Uncontrolled high blood pressure Abnormal kidney function (with-eGFR, a measure of kidney function, of 25 - ≤ 45 mL/min/1.73m2 Normal Blood serum Potassium in a specific range (4.3 - 5.1 mEq/L) Exclusion Criteria: History of untreated known causes of high blood pressure, excluding kidney disease (not CKD) Inability to measure BP Not taking high blood pressure medications as prescribed medications Recent change in renal function (in the past 3 months) which has required hospitalization or dialysis Renal transplant History of cancer within past 12 months Recent cardiovascular event with last 3 months Clinically significant abnormalities of heart rhythm (ventricular arrhythmia or atrial fibrillation with uncontrolled heart rate) Inability to take study medication Alcoholism
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director or VP Clinical Development
Organizational Affiliation
Relypsa, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Investigator Site 1012
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33021
Country
United States
Facility Name
Investigator Site 1023
City
Miami Lakes
State/Province
Florida
ZIP/Postal Code
33014
Country
United States
Facility Name
Investigator Site 1022
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Investigator Site 1402
City
Sofia
ZIP/Postal Code
1612
Country
Bulgaria
Facility Name
Investiagor Site 2205
City
Zagreb
ZIP/Postal Code
10000
Country
Croatia
Facility Name
Investigator Site 2201
City
Zagreb
ZIP/Postal Code
10000
Country
Croatia
Facility Name
Investigator Site 2202
City
Zagreb
ZIP/Postal Code
10000
Country
Croatia
Facility Name
Investigator Site 2203
City
Zagreb
ZIP/Postal Code
10000
Country
Croatia
Facility Name
Investigator Site 3806
City
Tbilisi
ZIP/Postal Code
0102
Country
Georgia
Facility Name
Investigator Site 3811
City
Tbilisi
ZIP/Postal Code
0112
Country
Georgia
Facility Name
Investigator Site 3802
City
Tbilisi
ZIP/Postal Code
0144
Country
Georgia
Facility Name
Investigator Site 3801
City
Tbilisi
ZIP/Postal Code
0159
Country
Georgia
Facility Name
Investigator Site 3804
City
Tbilisi
ZIP/Postal Code
0159
Country
Georgia
Facility Name
Investigator Site 3805
City
Tbilisi
ZIP/Postal Code
0159
Country
Georgia
Facility Name
Investigator Site 3807
City
Tbilisi
ZIP/Postal Code
0159
Country
Georgia
Facility Name
Investigator Site 3808
City
Tbilisi
ZIP/Postal Code
0159
Country
Georgia
Facility Name
Investigator Site 3810
City
Tbilisi
ZIP/Postal Code
0159
Country
Georgia
Facility Name
Investigator Site 3812
City
Tbilisi
ZIP/Postal Code
0159
Country
Georgia
Facility Name
Investigator Site 3813
City
Tbilisi
ZIP/Postal Code
0159
Country
Georgia
Facility Name
Investigator Site 3809
City
Tbilisi
ZIP/Postal Code
0186
Country
Georgia
Facility Name
Investigator Site 4202
City
Gottingen
ZIP/Postal Code
37075
Country
Germany
Facility Name
Investigator Site 4607
City
Balatonfured
ZIP/Postal Code
H-8230
Country
Hungary
Facility Name
Investigator Site 4606
City
Budapest
ZIP/Postal Code
H-1097
Country
Hungary
Facility Name
Investigator Site 4611
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
Facility Name
Investigator Site 4601
City
Hatvan
ZIP/Postal Code
H-3000
Country
Hungary
Facility Name
Investigator Site 4605
City
Kistarcsa
ZIP/Postal Code
H-2143
Country
Hungary
Facility Name
Investigator Site 4602
City
Miskolc
ZIP/Postal Code
H-3529
Country
Hungary
Facility Name
Investigator Site 4610
City
Miskolc
ZIP/Postal Code
H-3530
Country
Hungary
Facility Name
Investigator Site 4608
City
Mosonmagyarovar
ZIP/Postal Code
H-9200
Country
Hungary
Facility Name
Investigator Site 7403
City
Johannesburg
Country
South Africa
Facility Name
Investigator Site 7803
City
Khar'kov
ZIP/Postal Code
61006
Country
Ukraine
Facility Name
Investiagor Site 7809
City
Kharkiv
ZIP/Postal Code
61002
Country
Ukraine
Facility Name
Investigator Site 7808
City
Kharkiv
ZIP/Postal Code
61039
Country
Ukraine
Facility Name
Investigator Site 7802
City
Kharkiv
ZIP/Postal Code
61103
Country
Ukraine
Facility Name
Investigator Site 7805
City
Kiev
ZIP/Postal Code
03680
Country
Ukraine
Facility Name
Investigator Site 7801
City
Kiev
ZIP/Postal Code
04114
Country
Ukraine
Facility Name
Investigator Site 7804
City
Zaporizhzhia
ZIP/Postal Code
69001
Country
Ukraine
Facility Name
Investigator Site 7807
City
Zaporizhzhia
ZIP/Postal Code
69118
Country
Ukraine
Facility Name
Investigator Site 8202
City
Leicester
ZIP/Postal Code
LE5 4QF
Country
United Kingdom
Facility Name
Investigator Site 8205
City
London
ZIP/Postal Code
Se5 9RS
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35369022
Citation
Agarwal R, Rossignol P, Budden J, Mayo MR, Arthur S, Williams B, White WB. Patiromer and Spironolactone in Resistant Hypertension and Advanced CKD: Analysis of the Randomized AMBER Trial. Kidney360. 2021 Jan 15;2(3):425-434. doi: 10.34067/KID.0006782020. eCollection 2021 Mar 25.
Results Reference
derived
PubMed Identifier
32588430
Citation
Natale P, Palmer SC, Ruospo M, Saglimbene VM, Strippoli GF. Potassium binders for chronic hyperkalaemia in people with chronic kidney disease. Cochrane Database Syst Rev. 2020 Jun 26;6(6):CD013165. doi: 10.1002/14651858.CD013165.pub2.
Results Reference
derived
PubMed Identifier
31533906
Citation
Agarwal R, Rossignol P, Romero A, Garza D, Mayo MR, Warren S, Ma J, White WB, Williams B. 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. Lancet. 2019 Oct 26;394(10208):1540-1550. doi: 10.1016/S0140-6736(19)32135-X. Epub 2019 Sep 15.
Results Reference
derived
PubMed Identifier
30176673
Citation
Agarwal R, Rossignol P, Garza D, Mayo MR, Warren S, Arthur S, Romero A, White WB, Williams B. Patiromer to Enable Spironolactone Use in the Treatment of Patients with Resistant Hypertension and Chronic Kidney Disease: Rationale and Design of the AMBER Study. Am J Nephrol. 2018;48(3):172-180. doi: 10.1159/000492622. Epub 2018 Sep 3.
Results Reference
derived

Learn more about this trial

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

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