Clinical trial NCT03071263: Spironolactone With Patiromer in the Treatment of Resistant Hypertension in Chronic Kidney Disease
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hyperkalemia
Resistant Hypertension
Keywords: Treatment of Hyperkalemia
Hyperkalemia
Potassium
Chronic Kidney Disease
Hypertension
Resistant Hypertension
Spironolactone
Lead sponsor: Vifor Pharma
Sponsor class: INDUSTRY
First posted: 2017-03-06
Enrollment: 295
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants Remaining on Spironolactone at Week 12
timeFrame: At week 12
Secondary outcomes:
measure: 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
timeFrame: From baseline to Week 12
Other outcomes:
measure: Change in AOBP SBP From Baseline to Week 12 Regardless of Increase in Antihypertensives
timeFrame: From baseline to Week 12
measure: Central Serum Potassium Change From Baseline to Week 12 by Baseline Serum Potassium Category
timeFrame: From baseline to Week 12
measure: Participants With Central Serum Potassium <5.5 mEq/L Over Time
timeFrame: From baseline to Week 12
measure: Participants Having Spironolactone Titrations Over Time
timeFrame: From baseline to Week 12
measure: Number of Participants by Spironolactone Dose Prescribed at Each Visit
timeFrame: From baseline to Week 10
measure: Shifts in Selected Laboratory Tests From Baseline to End of Treatment
timeFrame: From Baseline to End of Treatment, up to 12 weeks.
measure: Spironolactone Dose Level at End of 12 Weeks of Study Treatment
timeFrame: 12 Weeks of Study Treatment
Locations:
city: Hollywood
country: United States
facility: Investigator Site 1012
state: Florida
city: Miami Lakes
country: United States
facility: Investigator Site 1023
state: Florida
city: Chicago
country: United States
facility: Investigator Site 1022
state: Illinois
city: Sofia
country: Bulgaria
facility: Investigator Site 1402
city: Zagreb
country: Croatia
facility: Investiagor Site 2205
city: Zagreb
country: Croatia
facility: Investigator Site 2201
city: Zagreb
country: Croatia
facility: Investigator Site 2202
city: Zagreb
country: Croatia
facility: Investigator Site 2203
city: Tbilisi
country: Georgia
facility: Investigator Site 3806
city: Tbilisi
country: Georgia
facility: Investigator Site 3811
city: Tbilisi
country: Georgia
facility: Investigator Site 3802
city: Tbilisi
country: Georgia
facility: Investigator Site 3801
city: Tbilisi
country: Georgia
facility: Investigator Site 3804
city: Tbilisi
country: Georgia
facility: Investigator Site 3805
city: Tbilisi
country: Georgia
facility: Investigator Site 3807
city: Tbilisi
country: Georgia
facility: Investigator Site 3808
city: Tbilisi
country: Georgia
facility: Investigator Site 3810
city: Tbilisi
country: Georgia
facility: Investigator Site 3812
city: Tbilisi
country: Georgia
facility: Investigator Site 3813
city: Tbilisi
country: Georgia
facility: Investigator Site 3809
city: Gottingen
country: Germany
facility: Investigator Site 4202
city: Balatonfured
country: Hungary
facility: Investigator Site 4607
city: Budapest
country: Hungary
facility: Investigator Site 4606
city: Debrecen
country: Hungary
facility: Investigator Site 4611
city: Hatvan
country: Hungary
facility: Investigator Site 4601
city: Kistarcsa
country: Hungary
facility: Investigator Site 4605
city: Miskolc
country: Hungary
facility: Investigator Site 4602
city: Miskolc
country: Hungary
facility: Investigator Site 4610
city: Mosonmagyarovar
country: Hungary
facility: Investigator Site 4608
city: Johannesburg
country: South Africa
facility: Investigator Site 7403
city: Khar'kov
country: Ukraine
facility: Investigator Site 7803
city: Kharkiv
country: Ukraine
facility: Investiagor Site 7809
city: Kharkiv
country: Ukraine
facility: Investigator Site 7808
city: Kharkiv
country: Ukraine
facility: Investigator Site 7802
city: Kiev
country: Ukraine
facility: Investigator Site 7805
city: Kiev
country: Ukraine
facility: Investigator Site 7801
city: Zaporizhzhia
country: Ukraine
facility: Investigator Site 7804
city: Zaporizhzhia
country: Ukraine
facility: Investigator Site 7807
city: Leicester
country: United Kingdom
facility: Investigator Site 8202
city: London
country: United Kingdom
facility: Investigator Site 8205
Study officials:
affiliation: Relypsa, Inc.
name: Study Director or VP Clinical Development
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.