Randomized Placebo-Controlled EPPIC Trials of AST-120 in CKD

Area of Science:

• Nephrology
• Clinical Pharmacology
• Internal Medicine

Background:

• Reduced glomerular filtration rate (GFR) in chronic kidney disease (CKD) leads to uremic toxin accumulation, worsening disease progression and morbidity.
• AST-120, an oral spherical carbon adsorbent, aims to reduce systemic toxin absorption via gastrointestinal sequestration.
• The potential benefit of AST-120 in slowing CKD progression warrants investigation.

Purpose of the Study:

• To evaluate the efficacy of AST-120, when added to standard therapy, in slowing the progression of moderate to severe CKD.
• To assess the impact of AST-120 on key composite endpoints including dialysis initiation, kidney transplantation, and serum creatinine doubling.

Main Methods:

• Multinational, randomized, double-blind, placebo-controlled trials (EPPIC-1 and EPPIC-2) involving 2035 adult patients with moderate to severe CKD.
• Patients received either AST-120 (9 g/d) or a placebo, alongside standard CKD therapy.
• The primary endpoint was a composite of dialysis initiation, kidney transplantation, or doubling of serum creatinine, with trials continuing until 291 primary endpoints accrued per trial.

Main Results:

• The time to the primary composite endpoint was statistically similar between the AST-120 and placebo groups in both EPPIC-1 (HR, 1.03; P=0.78) and EPPIC-2 (HR, 0.91; P=0.37).
• A pooled analysis of both trials confirmed no significant difference in disease progression between the treatment arms.
• Actual median times to primary endpoints were longer than anticipated, suggesting a more gradual disease progression in the study populations than expected.

Conclusions:

• Adding AST-120 to standard therapy did not demonstrate a significant benefit in slowing the progression of moderate to severe CKD in the evaluated patient populations.
• The study data do not support the use of AST-120 for delaying key CKD progression events like dialysis or transplantation.
• Further research may be needed to explore alternative therapeutic strategies for managing CKD progression.