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

Hyperkalemia Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03071263
• Other study ID #: RLY5016-207
• Secondary ID: 2016-002657-38
• Status: Completed
• Phase: Phase 2
• Start date: January 23, 2017
• Est. completion date: November 27, 2018

Study information

• Verified date: May 2021
• Source: Vifor Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 295
• Est. completion date: November 27, 2018
• Est. primary completion date: November 27, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hyperkalemia
• Hypertension
• Kidney Diseases
• Renal Insufficiency, Chronic
• Resistant Hypertension

Intervention

Drug:
• Patiromer
2 packets/day starting dose, administered orally
• Placebo
2 packets/day starting dose, administered orally
• Spironolactone
25 mg tablet/day starting dose, administered orally

Locations

Country	Name	City	State
Bulgaria	Investigator Site 1402	Sofia
Croatia	Investiagor Site 2205	Zagreb
Croatia	Investigator Site 2201	Zagreb
Croatia	Investigator Site 2202	Zagreb
Croatia	Investigator Site 2203	Zagreb
Georgia	Investigator Site 3801	Tbilisi
Georgia	Investigator Site 3802	Tbilisi
Georgia	Investigator Site 3804	Tbilisi
Georgia	Investigator Site 3805	Tbilisi
Georgia	Investigator Site 3806	Tbilisi
Georgia	Investigator Site 3807	Tbilisi
Georgia	Investigator Site 3808	Tbilisi
Georgia	Investigator Site 3809	Tbilisi
Georgia	Investigator Site 3810	Tbilisi
Georgia	Investigator Site 3811	Tbilisi
Georgia	Investigator Site 3812	Tbilisi
Georgia	Investigator Site 3813	Tbilisi
Germany	Investigator Site 4202	Gottingen
Hungary	Investigator Site 4607	Balatonfured
Hungary	Investigator Site 4606	Budapest
Hungary	Investigator Site 4611	Debrecen
Hungary	Investigator Site 4601	Hatvan
Hungary	Investigator Site 4605	Kistarcsa
Hungary	Investigator Site 4602	Miskolc
Hungary	Investigator Site 4610	Miskolc
Hungary	Investigator Site 4608	Mosonmagyarovar
South Africa	Investigator Site 7403	Johannesburg
Ukraine	Investigator Site 7803	Khar'kov
Ukraine	Investiagor Site 7809	Kharkiv
Ukraine	Investigator Site 7802	Kharkiv
Ukraine	Investigator Site 7808	Kharkiv
Ukraine	Investigator Site 7801	Kiev
Ukraine	Investigator Site 7805	Kiev
Ukraine	Investigator Site 7804	Zaporizhzhia
Ukraine	Investigator Site 7807	Zaporizhzhia
United Kingdom	Investigator Site 8202	Leicester
United Kingdom	Investigator Site 8205	London
United States	Investigator Site 1022	Chicago	Illinois
United States	Investigator Site 1012	Hollywood	Florida
United States	Investigator Site 1023	Miami Lakes	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Relypsa, Inc.

Countries where clinical trial is conducted

United States,  Bulgaria,  Croatia,  Georgia,  Germany,  Hungary,  South Africa,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in AOBP SBP From Baseline to Week 12 Regardless of Increase in Antihypertensives	AOBP SBP: Automated Office Systolic Blood Pressure	From baseline to Week 12
Other	Central Serum Potassium Change From Baseline to Week 12 by Baseline Serum Potassium Category	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.	From baseline to Week 12
Other	Participants With Central Serum Potassium <5.5 mEq/L Over Time	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.	From baseline to Week 12
Other	Participants Having Spironolactone Titrations Over Time	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)].	From baseline to Week 12
Other	Number of Participants by Spironolactone Dose Prescribed at Each Visit	QD: Once daily; QOD: Once every other day	From baseline to Week 10
Other	Shifts in Selected Laboratory Tests From Baseline to End of Treatment	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	From Baseline to End of Treatment, up to 12 weeks.
Other	Spironolactone Dose Level at End of 12 Weeks of Study Treatment	Row title: Participants not completing 12W of study treatment: Participants who had not completed 12 weeks of study treatment.	12 Weeks of Study Treatment
Primary	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.	At week 12
Secondary	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	From baseline to Week 12