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

NCT03071263 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: RLY5016-2072016-002657-38
• Study Type: interventional
• Target: 295
• Locations: 9 countries
• Sites: 40

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).

Conditions

Hyperkalemia; Resistant Hypertension

Keywords

Treatment of Hyperkalemia; Hyperkalemia; Potassium; Chronic Kidney Disease; Hypertension; Resistant Hypertension; Spironolactone

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (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

  From baseline to Week 12

Other Outcomes (7)

• Change in AOBP SBP From Baseline to Week 12 Regardless of Increase in Antihypertensives

  From baseline to Week 12

• Central Serum Potassium Change From Baseline to Week 12 by Baseline Serum Potassium Category

  From baseline to Week 12

• Participants With Central Serum Potassium <5.5 mEq/L Over Time

  From baseline to Week 12

Study Arms (2)

Group 1 - Patiromer

EXPERIMENTAL

spironolactone + blinded patiromer

Drug: Patiromer; Drug: Spironolactone

Group 2 - Placebo

EXPERIMENTAL

spironolactone + blinded placebo

Drug: Placebo; Drug: Spironolactone

Interventions

Patiromer DRUG

2 packets/day starting dose, administered orally

Also known as: Veltassa, RLY5016 for Oral Suspension, Patiromer for Oral Suspension

Group 1 - Patiromer

Placebo DRUG

2 packets/day starting dose, administered orally

Group 2 - Placebo

Spironolactone DRUG

25 mg tablet/day starting dose, administered orally

Group 1 - Patiromer; Group 2 - Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Relypsa, Inc.: lead

Study Sites (40)

Investigator Site 1012

Hollywood, Florida, 33021, United States

Location

Investigator Site 1023

Miami Lakes, Florida, 33014, United States

Location

Investigator Site 1022

Chicago, Illinois, 60611, United States

Location

Investigator Site 1402

Sofia, 1612, Bulgaria

Location

Investiagor Site 2205

Zagreb, 10000, Croatia

Location

Investigator Site 2201

Zagreb, 10000, Croatia

Location

Investigator Site 2202

Zagreb, 10000, Croatia

Location

Investigator Site 2203

Zagreb, 10000, Croatia

Location

Investigator Site 3806

Tbilisi, 0102, Georgia

Location

Investigator Site 3811

Tbilisi, 0112, Georgia

Location

Investigator Site 3802

Tbilisi, 0144, Georgia

Location

Investigator Site 3801

Tbilisi, 0159, Georgia

Location

Investigator Site 3804

Tbilisi, 0159, Georgia

Location

Investigator Site 3805

Tbilisi, 0159, Georgia

Location

Investigator Site 3807

Tbilisi, 0159, Georgia

Location

Investigator Site 3808

Tbilisi, 0159, Georgia

Location

Investigator Site 3810

Tbilisi, 0159, Georgia

Location

Investigator Site 3812

Tbilisi, 0159, Georgia

Location

Investigator Site 3813

Tbilisi, 0159, Georgia

Location

Investigator Site 3809

Tbilisi, 0186, Georgia

Location

Investigator Site 4202

Göttingen, 37075, Germany

Location

Investigator Site 4607

Balatonfüred, H-8230, Hungary

Location

Investigator Site 4606

Budapest, H-1097, Hungary

Location

Investigator Site 4611

Debrecen, 4032, Hungary

Location

Investigator Site 4601

Hatvan, H-3000, Hungary

Location

Investigator Site 4605

Kistarcsa, H-2143, Hungary

Location

Investigator Site 4602

Miskolc, H-3529, Hungary

Location

Investigator Site 4610

Miskolc, H-3530, Hungary

Location

Investigator Site 4608

Mosonmagyaróvár, H-9200, Hungary

Location

Investigator Site 7403

Johannesburg, South Africa

Location

Investiagor Site 7809

Kharkiv, 61002, Ukraine

Location

Investigator Site 7803

Kharkiv, 61006, Ukraine

Location

Investigator Site 7808

Kharkiv, 61039, Ukraine

Location

Investigator Site 7802

Kharkiv, 61103, Ukraine

Location

Investigator Site 7805

Kiev, 03680, Ukraine

Location

Investigator Site 7801

Kiev, 04114, Ukraine

Location

Investigator Site 7804

Zaporizhzhia, 69001, Ukraine

Location

Investigator Site 7807

Zaporizhzhia, 69118, Ukraine

Location

Investigator Site 8202

Leicester, LE5 4QF, United Kingdom

Location

Investigator Site 8205

London, Se5 9RS, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 35369022 DERIVED

• 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.

  PMID: 32588430 DERIVED

• 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.

  PMID: 31533906 DERIVED

• 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.

  PMID: 30176673 DERIVED

MeSH Terms

Conditions

Hyperkalemia; Renal Insufficiency, Chronic; Hypertension

Interventions

patiromer; Suspensions; Spironolactone

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations; Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Clinical Support & Regulatory Intelligence, Regulatory Affairs Director
• Organization: Vifor Pharma Inc.

Clive.Burge@viforpharma.com

+1 250 708 4296

Study Officials

• Study Director or VP Clinical Development

  Relypsa, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2017
• First Posted: March 6, 2017
• Study Start: January 23, 2017
• Primary Completion: November 27, 2018
• Study Completion: November 27, 2018
• Last Updated: May 12, 2021
• Results First Posted: January 27, 2020

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

HU (8); UA (8); GB (2); CR (4); GE (12); ZA (1); BU (1); US (3); DE (1)