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

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ClinicalTrials.gov Identifier: NCT03071263
Recruitment Status : Completed
First Posted : March 6, 2017
Results First Posted : January 27, 2020
Last Update Posted : May 12, 2021
Sponsor:
Information provided by (Responsible Party):
Vifor Pharma ( Relypsa, Inc. )

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).

Condition or disease Intervention/treatment Phase
Hyperkalemia Resistant Hypertension Drug: Patiromer Drug: Placebo Drug: Spironolactone Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 295 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : January 23, 2017
Actual Primary Completion Date : November 27, 2018
Actual Study Completion Date : November 27, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases

Arm Intervention/treatment
Experimental: Group 1 - Patiromer
spironolactone + blinded patiromer
Drug: Patiromer
2 packets/day starting dose, administered orally
Other Names:
  • Veltassa
  • RLY5016 for Oral Suspension
  • Patiromer for Oral Suspension

Drug: Spironolactone
25 mg tablet/day starting dose, administered orally

Experimental: Group 2 - Placebo
spironolactone + blinded placebo
Drug: Placebo
2 packets/day starting dose, administered orally

Drug: Spironolactone
25 mg tablet/day starting dose, administered orally




Primary Outcome Measures :
  1. Number of Participants Remaining on Spironolactone at Week 12 [ Time Frame: 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 :
  1. 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 [ Time Frame: From baseline to Week 12 ]
    AOBP: Automated Office Blood Pressure SBP: Systolic Blood Pressure BP: Blood Pressure


Other Outcome Measures:
  1. Change in AOBP SBP From Baseline to Week 12 Regardless of Increase in Antihypertensives [ Time Frame: From baseline to Week 12 ]
    AOBP SBP: Automated Office Systolic Blood Pressure

  2. Central Serum Potassium Change From Baseline to Week 12 by Baseline Serum Potassium Category [ Time Frame: 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.


  3. Participants With Central Serum Potassium <5.5 mEq/L Over Time [ Time Frame: 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.


  4. Participants Having Spironolactone Titrations Over Time [ Time Frame: 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)].


  5. Number of Participants by Spironolactone Dose Prescribed at Each Visit [ Time Frame: From baseline to Week 10 ]

    QD: Once daily

    QOD: Once every other day


  6. Shifts in Selected Laboratory Tests From Baseline to End of Treatment [ Time Frame: 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


  7. Spironolactone Dose Level at End of 12 Weeks of Study Treatment [ Time Frame: 12 Weeks of Study Treatment ]

    Row title:

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




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03071263


Locations
Show Show 40 study locations
Sponsors and Collaborators
Relypsa, Inc.
Investigators
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Study Director: Study Director or VP Clinical Development Relypsa, Inc.
  Study Documents (Full-Text)

Documents provided by Vifor Pharma ( Relypsa, Inc. ):
Study Protocol  [PDF] November 4, 2016
Statistical Analysis Plan  [PDF] December 11, 2018

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Relypsa, Inc.
ClinicalTrials.gov Identifier: NCT03071263    
Other Study ID Numbers: RLY5016-207
2016-002657-38 ( EudraCT Number )
First Posted: March 6, 2017    Key Record Dates
Results First Posted: January 27, 2020
Last Update Posted: May 12, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Vifor Pharma ( Relypsa, Inc. ):
Treatment of Hyperkalemia
Hyperkalemia
Potassium
Chronic Kidney Disease
Hypertension
Resistant Hypertension
Spironolactone
Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency, Chronic
Hypertension
Hyperkalemia
Vascular Diseases
Cardiovascular Diseases
Urologic Diseases
Renal Insufficiency
Water-Electrolyte Imbalance
Metabolic Diseases
Spironolactone
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents