Phase 3
Completed N=754
Safety & Efficacy of Zirconium Silicate in Mild to Moderate Hyperkalemia
Source: ClinicalTrials.gov NCT01737697 ↗Enrolled (actual)
754
Serious AEs
1.2%
Results posted
Oct 2018
Primary outcomePrimary: Exponential Rate of Change in Serum Potassium (S-K) Levels During the Initial 48 Hours of Study Drug Treatment. — -0.00128; -0.00187; -0.00205; -0.00280 log(mmol/L)/hour
◆ Published Evidence
Highly cited
495citations · ~45 / year
Sodium zirconium cyclosilicate in hyperkalemia.
Summary
Acute Phase: It is hypothesized that ZS (zirconium silicate) is more effective than placebo control (alternative hypothesis) in lowering S-K levels in subjects with S-K between 5.0 - 6.5 mmol/l versus no difference between ZS and placebo control (null hypothesis).
Subacute Phase (randomized withdrawal): It is hypothesized that ZS once daily is more effective than placebo control (alternative hypotheses) in maintaining normokalemic levels (3.5 - 4.9 mmol/l) among subjects completing the Acute Phase versus no difference between each ZS dose and respective placebo controls (null hypotheses).
Linked Publications (4)
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Sodium zirconium cyclosilicate in hyperkalemia.
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Potassium binders for chronic hyperkalaemia in people with chronic kidney disease.
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Efficacy and safety of sodium zirconium cyclosilicate in patients with baseline serum potassium level ≥ 5.5 mmol/L: pooled analysis from two phase 3 trials.
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Errors of Classification With Potassium Blood Testing: The Variability and Repeatability of Critical Clinical Tests.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Exponential Rate of Change in Serum Potassium (S-K) Levels During the Initial 48 Hours of Study Drug Treatment. |
-0.00128; -0.00187; -0.00205; -0.00280; -0.00382; -0.00097 | — |
| PRIMARY Exponential Rate of Change in S-K Levels in the Subacute Phase. |
0.00054; 0.00874; 0.01104; 0.00734; 0.01441; 0.00581 | — |
| SECONDARY Percentage of Subjects Who Achieve Normalization in S-K Levels After 48 Hours of Treatment |
47.8; 51.3; 67.9; 77.6; 86.4 | — |
| SECONDARY Mean Change From Baseline in S-K at All Time Points Acute Phase |
5.30; 5.37; 5.35; 5.31; 5.26; 0.01 | — |
| SECONDARY Mean Percent Change From Baseline in S-K Change at All Time Points Acute Phase |
0.09; -0.23; -1.37; -1.13; -2.08; 0.03 | — |
| SECONDARY Time Subjects Remain Normokalemic (Subacute Phase) |
7.6; 7.2; 6.2; 8.6; 6.0; 9.0 | — |
| SECONDARY Percentage of Subjects Within Each Treatment Group Who Retained Normal S-K Values at End of Subacute Phase |
73.2; 59.2; 65.2; 64.8; 54.4; 57.8 | — |
| SECONDARY Mean Change From Subacute Baseline in Serum Potassium at All Time Points. |
5.22; 5.29; 5.25; 5.23; 5.31; 5.24 | — |
| SECONDARY Mean Percent Change From Subacute Baseline in Serum Potassium at All Time Points. |
0.66; 3.31; 4.74; 2.58; 2.03; 2.90 | — |
Eligibility Criteria
Inclusion Criteria
- Provision of written informed consent.
- Over 18 years of age.
- Mean i-STAT potassium values between 5.0 - 6.5 mmol/l inclusive, at screening (Study Day 0).
- Ability to have repeated blood draws or effective venous catheterization.
- Women of childbearing potential must be practicing a highly effective method of birth control.
Exclusion Criteria
- Pseudohyperkalemia signs and symptoms, such as excessive fist clinching hemolyzed blood specimen, severe leukocytosis or thrombocytosis.
- Subjects treated with lactulose, xifaxan or other nonabsorbed antibiotics for hyperammonemia within the last 7 days.
- Subjects treated with resins (such as Sevelamer acetate or Sodium polystyrene sulfonate [SPS; e.g. Kayexalate®]), calcium acetate, calcium carbonate, or lanthanum carbonate, within the last 7 days.
- Subjects with a life expectancy of less than 3 months.
- Subjects who are HIV positive.
- Subjects who are severely physically or mentally incapacitated and who in the opinion of investigator are unable to perform the subjects' tasks associated with the protocol.
- Women who are pregnant, lactating, or planning to become pregnant.
- Subjects with Ketoacidosis/Acidemia.
- Presence of any condition which, in the opinion of the investigator, places the subject at undue risk or potentially jeopardizes the quality of the data to be generated.
- Known hypersensitivity or previous anaphylaxis to ZS or to components thereof.
- Previous treatment with ZS
- Treatment with a drug or device within the last 30 days that has not received regulatory approval at the time of study entry.
- Subjects with cardiac arrhythmias that require immediate treatment.
- Insulin-dependent diabetes mellitus
- Subjects on dialysis
Data sourced from ClinicalTrials.gov (NCT01737697) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.