Spironolactone With Patiromer in the Treatment of Resistant Hypertension in Chronic Kidney Disease (AMBER)
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| ClinicalTrials.gov Identifier: NCT03071263 |
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Recruitment Status :
Completed
First Posted : March 6, 2017
Results First Posted : January 27, 2020
Last Update Posted : May 12, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hyperkalemia Resistant Hypertension | Drug: Patiromer Drug: Placebo Drug: Spironolactone | Phase 2 |
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.
| 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 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Group 1 - Patiromer
spironolactone + blinded patiromer
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Drug: Patiromer
2 packets/day starting dose, administered orally
Other Names:
Drug: Spironolactone 25 mg tablet/day starting dose, administered orally |
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Experimental: Group 2 - Placebo
spironolactone + blinded placebo
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Drug: Placebo
2 packets/day starting dose, administered orally Drug: Spironolactone 25 mg tablet/day starting dose, administered orally |
- 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.
- 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
- 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
- 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.
- 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.
- 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)].
- 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
- 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
- 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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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
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| Study Director: | Study Director or VP Clinical Development | Relypsa, Inc. |
Documents provided by Vifor Pharma ( Relypsa, Inc. ):
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Treatment of Hyperkalemia Hyperkalemia Potassium Chronic Kidney Disease |
Hypertension Resistant Hypertension Spironolactone |
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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 |