safety and efficacy of sodium polystyrene sulfonate in hyperkalemia

Conditions: Hyperkalemia

Summary: it is hypothesized that sps is more effective than placebo control (alternative hypothesis) in lowering i-stat potassium levels in subjects with i-stat potassium levels between 5.0 - 6.5 mmol/l versus no difference between sps and placebo control (null hypothesis).

subjects with mild to moderate hyperkalemia (i-stat potassium levels between 5.0-6.5 mmol/l, inclusive) will be randomized 1:1 in a double-blind fashion to receive placebo or sps (15g), administered tid with meals for 48 hours. subjects will come back to the clinic on study day 9 for an end of study (eos) visit. adverse experiences will be recorded. blood potassium levels will be evaluated by both i-stat and the local laboratory prior to the first dose on study days 1 and 2, 1, 2, and 4 hours after the first dose on study day 1, 1 and 4 hours after the first dose on study day 2 and prior to breakfast on study day 3, after 48 hours of treatment. subjects who have i-stat potassium levels \> 6.5 mmol/l on study day 1 at the 4 hour post dose 1 time point will be withdrawn from the study and will receive standard of care. if the i-stat potassium value is between 6.1 and 6.5 mmol/l at the 4-hour post dose 1 draw, subjects will be kept in the clinic for another 90 minutes post dose 2 and another blood draw will be taken and an ecg will be performed. if the i-stat potassium level is ≥ 6.2 mmol/l at this time point, the subject will be discontinued from the study and standard of care will be instituted. if the i-stat potassium level is \< 6.2 mmol/l, and the ecg does not show any of the ecg withdrawal criteria (see below), the subject will continue in the study.

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). * previous participation in clinical zs-002 or zs-003 protocol(s). however, subjects cannot be enrolled in this study until at least 30 days have elapsed from their last dose in study zs-003. * ability to have repeated blood draws or effective venous catheterization. * women of childbearing potential must be using two forms of medically acceptable contraception (at least one barrier method) and have a negative pregnancy test at screening. women who are surgically sterile or those who are post-menopausal for at least 2 years are not considered to be of child-bearing potential. exclusion criteria: * pseudohyperkalemia signs and symptoms, such as excessive fist clenching hemolyzed blood specimen, severe leukocytosis or thrombocytosis. * subjects treated with lactulose, xifaxan or other non-absorbed antibiotics for hyperammonemia within the last 7 days. * subjects treated with resins (such as sevelamer acetate), calcium acetate, calcium carbonate, or lanthanum carbonate, within the last 7 days. * subjects treated with sodium polystyrene sulfonate (sps; e.g. kayexalate®) or zs (microporous, fractionated, protonated zirconium silicate) within the last 30 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 diabetic ketoacidosis. * 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 sps. * 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. * subjects on insulin where a stable dose has not yet been established.\* * subjects on dialysis. \* subjects on stable insulin or insulin analogues can be enrolled. subjects who have been on the same insulin dose and regimen for \> 14 days are considered stable. whenever possible, all blood draws collected prior to meals should be collected prior to insulin/insulin analogue treatment.