Clinical trial NCT03303521: A Study to Test Whether ZS (Sodium Zirconium Cyclosilicate) Can Reduce the Incidence of Increased Blood Potassium Levels Among Dialized Patients.
Official title: A Phase 3b, Multicenter, Prospective, Randomized, Double Blind, Placebocontrolled Study to Reduce Incidence of Pre-dialysis Hyperkalemia With Sodium Zirconium Cyclosilicate (DIALIZE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hyperkalemia
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2017-10-06
Enrollment: 196
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
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 evaluate the efficacy of ZS in the treatment of hyperkalemia in patients on hemodialysis.


Eligibility criteria: Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures
2. Female or male aged ≥ 18 years at screening Visit 1. For patients aged \<20 years and enrolled in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative.
3. Receiving hemodialysis (or hemodiafiltration) 3 times a week for treatment of endstage renal disease (ESRD) for at least 3 months before randomization.
4. Patients must have hemodialysis access consisting of an arteriovenous fistula, AV graft, or tunneled (permanent) catheter which is expected to remain in place for the entire duration of the study.
5. Pre-dialysis serum K \>5.4 mmol/L after long inter-dialytic interval and \>5.0 mmol/L after one short inter-dialytic interval during screening (as assessed by central lab).
6. Prescribed dialysate K concentration ≤ 3 mmol/L during screening
7. Sustained Qb ≥200 ml/min and spKt/V ≥1.2 (or URR ≥ 63) on stable hemodialysis/hemodiafltration prescription during screening with prescription (time, dialyzer, blood flow \[Qb\], dialysate flow rate \[Qd\] and bicarbonate concentration) expected to remain unchanged during study
8. Heparin dose (if used) must be stable during screening and expected to be stable during the study
9. Subjects must be receiving dietary counseling appropriate for ESRD patients treated with hemodialysis/hemodiafiltration as per local guidelines, which includes dietary potassium restriction.

Exclusion Criteria:

1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca, including ZS Pharma staff and/or staff at the study site)
2. Hemoglobin \<9 g/dL on screening (as assessed on Visit 1)
3. Lack of compliance with hemodialysis prescription (both number and duration of treatments) during the two-week period preceding screening (100% compliance required)
4. Patients treated with sodium polystyrene sulfonate (SPS, Kayexalate, Resonium), calcium polystyrene sulfonate (CPS, Resonium calcium) or patiromer (Veltassa) within 7 days before screening or anticipated in requiring any of these agents during the study
5. Myocardial infarction, acute coronary syndrome, stroke, seizure or a thrombotic/thromboembolic event (e.g., deep vein thrombosis or pulmonary embolism, but excluding vascular access thrombosis) within 12 weeks prior to randomization
6. Laboratory diagnosis of hypokalemia (K \< 3.5 mmol/L), hypocalcemia (Ca \< 8.2 mg/dL; for Japan hypocalcemia is defined as albumin-corrected Ca \< 8.0 mg/dL), hypomagnesemia (Mg \< 1.7 mg/dL) or severe acidosis (serum bicarbonate 16 mEq/L or less) in the 4 weeks preceding randomization
7. Pseudohyperkalemia secondary to hemolyzed blood specimen (this situation is not considered screening failure, sampling or full screening can be postponed to a later time as applicable).
8. Severe leukocytosis (\>20× 10\^9/L) or thrombocytosis (≥450 × 10\^9/L) during screening
9. Polycythemia (Hb \>14 g/dL) during screening
10. Diagnosis of rhabdomyolysis during the 4 weeks preceding randomization
11. Patients treated with lactulose, xifaxan (rifaximin) or other non-absorbed antibiotics for hyperammonemia within 7 days prior to the first dose of study drug
12. Patients unable to take oral ZS drug mix
13. Scheduled date for living donor kidney transplant
14. Patients with a life expectancy of less than 6 months
15. Female patients who are pregnant or breastfeeding
16. Females of childbearing potential, unless using contraception as detailed in the protocol or sexual abstinence.
17. Known hypersensitivity or previous anaphylaxis to ZS or to components thereof
18. Participation in another clinical study with an investigational product during the last 1 month before screening
19. Any medical condition, including active, clinically significant infection, that in the opinion of the investigator or Sponsor may pose a safety risk to a patient in this study, which may confound safety or efficacy assessment and jeopardize the quality of the data, or may interfere with study participation
20. Presence of cardiac arrhythmias or conduction defects that require immediate treatment
21. History of alcohol or drug abuse within 2 years prior to randomization
22. Previous randomization in the present study

Primary outcomes:
measure: Percentage of Responders
timeFrame: Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks, starting after visit 11 and ending on visit 15, thus it comprises post-long inter-dialytic interval visits 12, 13, 14 and 15.
measure: Percentage of Responders When Accounting for Missing Central Laboratory Serum Potassium Data
timeFrame: Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks, starting after visit 11 and ending on visit 15, thus it comprises post-long inter-dialytic interval visits 12, 13, 14 and 15.
Secondary outcomes:
measure: Percentage of Patients Needing Rescue Therapy
timeFrame: An 8 week overall treatment period (a 4 week adjustment phase plus a 4 week evaluation phase) and a 2 week follow up period.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Ontario
country: United States
facility: Research Site
state: California
city: San Dimas
country: United States
facility: Research Site
state: California
city: Whittier
country: United States
facility: Research Site
state: California
city: Kansas City
country: United States
facility: Research Site
state: Missouri
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Paterson
country: United States
facility: Research Site
state: New Jersey
city: Bronx
country: United States
facility: Research Site
state: New York
city: Fresh Meadows
country: United States
facility: Research Site
state: New York
city: Great Neck
country: United States
facility: Research Site
state: New York
city: Ridgewood
country: United States
facility: Research Site
state: New York
city: East Providence
country: United States
facility: Research Site
state: Rhode Island
city: El Paso
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Hamamatsu-shi
country: Japan
facility: Research Site
city: Kumamoto-shi
country: Japan
facility: Research Site
city: Miyagi-gun
country: Japan
facility: Research Site
city: Nagano-shi
country: Japan
facility: Research Site
city: Niigata-shi
country: Japan
facility: Research Site
city: Ora-gun
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Sakai-shi
country: Japan
facility: Research Site
city: Sashima-gun
country: Japan
facility: Research Site
city: Sendai-shi
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Toride-shi
country: Japan
facility: Research Site
city: Tsukuba-shi
country: Japan
facility: Research Site
city: Wakayama-shi
country: Japan
facility: Research Site
city: Yachiyo-shi
country: Japan
facility: Research Site
city: Yokosuka-shi
country: Japan
facility: Research Site
city: Kemerovo
country: Russian Federation
facility: Research Site
city: Kolomna
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Omsk
country: Russian Federation
facility: Research Site
city: Penza
country: Russian Federation
facility: Research Site
city: Podolsk
country: Russian Federation
facility: Research Site
city: Rostov-on-Don
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: St-Petersburg
country: Russian Federation
facility: Research Site
city: Yaroslavl
country: Russian Federation
facility: Research Site
city: Yekaterinburg
country: Russian Federation
facility: Research Site
city: Cardiff
country: United Kingdom
facility: Research Site
city: Hull
country: United Kingdom
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Swansea
country: United Kingdom
facility: Research Site
city: York
country: United Kingdom
facility: Research Site
Study officials:
affiliation: NSUH,Dept of Medicine,300 Community Drive,Manhasset,NY11030
name: Steven Fishbane, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fishbane S, Ford M, Fukagawa M, McCafferty K, Rastogi A, Spinowitz B, Staroselskiy K, Vishnevskiy K, Lisovskaja V, Al-Shurbaji A, Guzman N, Bhandari S. Potassium responses to sodium zirconium cyclosilicate in hyperkalemic hemodialysis patients: post-hoc analysis of DIALIZE. BMC Nephrol. 2022 Feb 8;23(1):59. doi: 10.1186/s12882-021-02569-7.
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.