Study of the Effect of SZC on Serum Potassium and Serum Bicarbonate in Patients With Hyperkalemia and Metabolic Acidosis Associated With Chronic Kidney Disease

NCT ID: NCT04727528

Last Updated: 2023-10-06

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

39 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-22

Study Completion Date

2022-09-14

Brief Summary

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The main objective of this study is to evaluate the efficacy of SZC as compared to placebo in maintaining normal sK+ in patients with hyperkalemia and metabolic acidosis associated with CKD

Detailed Description

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NEUTRALIZE is a prospective, randomized, double-blind, placebo-controlled, parallel, multicenter, Phase IIIb study to investigate the safety and efficacy of SZC in patients with hyperkalemia and low bicarbonate (metabolic acidosis ).

The study will be conducted in the United States (US) at approximately 35 investigative sites.

After screening on Day 1, all eligible patients will receive open-label SZC for up to 48 hours. Patients who achieve normokalemia within 48 hours will be randomized 1:1 into the double-blind randomized treatment phase to receive SZC or placebo. Study treatment will end with the Day 29 visit, which will be followed by a follow-up visit 7 days after the last administration of study medication.

Conditions

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Hyperkalaemia Metabolic Acidosis Chronic Kidney Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

NEUTRALIZE is a prospective, randomized, double-blind, placebo-controlled, parallel, multicenter, Phase IIIb study
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Open-label correction phase (up to 48 hours)

All eligible patients will receive SZC 10 g TID for up to 48 hours. Patients with POCT (Point-of-Care-Test) K+ ≥5.1 mmol/L after 24 hours will continue on SZC 10 g TID for another 24 hours. Patients who achieve normokalemia (defined as POCT K+ between 3.5 and 5.0 mmol/L inclusive) after receiving SZC 10 g TID for up to 48 hours will proceed to randomization.

Patients with POCT K+ \<3.5mmol/L at any time during the open-label phase will be withdrawn from study treatment and will be followed per protocol.

Group Type EXPERIMENTAL

Sodium zirconium cyclosilicate

Intervention Type DRUG

Investigational medicinal product

Placebo

Intervention Type DRUG

Plabeco comparator

Randomized, placebo controlled phase (Day 2 or 3 to Day 29)

Patients will be randomized to SZC 10 g QD or placebo 10 g QD. The dose of SZC/placebo will be titrated by increasing or decreasing the dose by 5 g increments at 1-week intervals to between 5 g every other day (QOD) and 15 g QD of the randomized phase to maintain normokalemia by POCT K+.

Group Type EXPERIMENTAL

Sodium zirconium cyclosilicate

Intervention Type DRUG

Investigational medicinal product

Placebo

Intervention Type DRUG

Plabeco comparator

Interventions

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Sodium zirconium cyclosilicate

Investigational medicinal product

Intervention Type DRUG

Placebo

Plabeco comparator

Intervention Type DRUG

Other Intervention Names

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SZC

Eligibility Criteria

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Inclusion Criteria

* Adults aged ≥18 years
* Participants who have CKD stage 3-5, not on dialysis.
* POCT K+ level \>5 mmol/L to ≤5.9 mmol/L and POCT bicarbonate levels between 16-20 mmol/L inclusive prior to the first SZC dose on study Day 1
* Ability to have repeated blood draws or effective venous catheterization.
* Male and/or female. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
* Capable of giving signed informed consent

Exclusion Criteria

* Participants with pseudohyperkalemia.
* Dialysis requirement or anticipated by the investigator to require dialysis therapy within 1 month, history of renal transplant, or life expectancy less than 3 months.
* Cardiac arrhythmias requiring immediate treatment.
* Active or suspected diabetic ketoacidosis.
* POCT bicarbonate low enough to need emergency intervention or treatment as judged by the investigator.
* Acute/chronic worsening renal function (eg, ≥30% decline in eGFR) in the 3 months before screening.
* Current acute decompensated HF, hospitalization due to decompensated HF within 4 weeks prior to screening, or myocardial infarction (MI), unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to screening.
* Coronary revascularization (percutaneous coronary intervention \[PCI\] or coronary artery bypass grafting \[CABG\]) or valvular repair/replacement within 12 weeks prior to screening or planned to undergo any of these operations.
* Symptomatic hypotension.
* Current exacerbation of chronic obstructive pulmonary disease (COPD)/asthma or hospitalization due to exacerbation of COPD/asthma within 4 weeks of screening.
* Severe constipation, bowel obstruction or impaction, including abnormal post-operative bowel motility disorders
* Active malignancy requiring treatment.
* History of QT prolongation associated with other medications that required discontinuation of that medication.
* Congenital long QT syndrome.
* Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Patients with atrial fibrillation controlled by medication are permitted.
* QTcF (QT interval corrected by the Fridericia method) \>550 msec.
* Active treatment (within 7 days prior to screening) with SZC, sodium bicarbonate, sodium polystyrene sulfonate, lactulose, or patiromer
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Florence, Alabama, United States

Site Status

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Chula Vista, California, United States

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Downey, California, United States

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El Centro, California, United States

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South Gate, California, United States

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Victorville, California, United States

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Aurora, Colorado, United States

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Denver, Colorado, United States

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Coral Gables, Florida, United States

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Columbus, Georgia, United States

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Hinsdale, Illinois, United States

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Kansas City, Missouri, United States

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Las Vegas, Nevada, United States

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The Bronx, New York, United States

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Asheville, North Carolina, United States

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New Bern, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Providence, Rhode Island, United States

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Spartanburg, South Carolina, United States

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Chattanooga, Tennessee, United States

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Memphis, Tennessee, United States

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Dallas, Texas, United States

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Dallas, Texas, United States

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San Antonio, Texas, United States

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Shenandoah, Texas, United States

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Alexandria, Virginia, United States

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Norfolk, Virginia, United States

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Bellevue, Washington, United States

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Milwaukee, Wisconsin, United States

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San Juan, , Puerto Rico

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Countries

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United States Puerto Rico

References

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Ash SR, Batlle D, Kendrick J, Oluwatosin Y, Kooienga L, Eudicone JM, Sundin AK, Guerrieri E, Fried LF. Sodium Zirconium Cyclosilicate in CKD, Hyperkalemia, and Metabolic Acidosis: NEUTRALIZE Randomized Study. Kidney360. 2024 Jun 1;5(6):812-820. doi: 10.34067/KID.0000000000000446. Epub 2024 Apr 16.

Reference Type DERIVED
PMID: 38622759 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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D9480C00022

Identifier Type: -

Identifier Source: org_study_id

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