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

Abstract

Reduced GFR in patients with CKD causes systemic accumulation of uremic toxins, which has been correlated with disease progression and increased morbidity. The orally administered spherical carbon adsorbent AST-120 reduces systemic toxin absorption through gastrointestinal sequestration, which may slow disease progression in these patients. The multinational, randomized, double-blind, placebocontrolled Evaluating Prevention of Progression in CKD (EPPIC)-1 and EPPIC-2 trials evaluated the effects of AST-120 on the progression of CKD when added to standard therapy. We randomly assigned 2035 adults with moderate to severe disease (serum creatinine at screening, 2.0-5.0 mg/dl for men and 1.5-5.0 mg/dl for women) to receive either placebo or AST-120 (9 g/d). The primary end point was a composite of dialysis initiation, kidney transplantation, and serum creatinine doubling. Each trial continued until accrual of 291 primary end points. The time to primary end point was similar between the AST-120 and the placebo groups in both trials (EPPIC-1: hazard ratio, 1.03; 95% confidence interval, 0.84 to 1.27; P=0.78) (EPPIC-2: hazard ratio, 0.91; 95% confidence interval, 0.74 to 1.12; P=0.37); a pooled analysis of both trials showed similar results. The estimated median time to primary end points for the placebo groups was 124 weeks for power calculations, but actual times were 189.0 and 170.3 weeks for EPPIC-1 and EPPIC-2, respectively. Thus, disease progression was more gradual than expected in the trial populations. In conclusion, the benefit of adding AST-120 to standard therapy in patients with moderate to severe CKD is not supported by these data. 26: 173226: -174626: , 201526: . doi: 10.1681 CKD, defined as kidney damage or a GFR,60 ml/min per 1.73 m 2 for $3 months, 1 is associated with increased risk for cardiovascular events, hospitalization, and death 2 and is a global public health problem. A meta-analysis of population-based studies from 40 countries and regions reported a 6.3% overall prevalence of CKD stages 3-5 (,60 ml/min per 1.73 m 2 ). 3 Furthermore, approximately 1870 cases of ESRD per million population were reported in 2010 compared with 1355 per million in 2000, 4 underscoring the need for treatments to slow or prevent the progression of CKD. J Am Soc NephrolEarly management of CKD is recommended to reduce cardiovascular events and additional complications of decreased GFR, improve quality of life, and prolong survival. 5 Current guidelines focus on managing factors that can hasten CKD progression, such as hypertension and diabetes. 6-8 Although angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) slow the progression of CKD, especially in patients

A Randomized, Controlled Trial of Oral Intestinal Sorbent AST-120 on Renal Function Deterioration in Patients with Advanced Renal Dysfunction

“…The Evaluating Prevention of Progression in CKD-1 and -2 Trials also revealed the same trend, and this trend was a potential cause of the negative results (27). In addition, the result of the CAP-KD Study was limited because of the infrequent primary end point events (18).…”

Effects of a novel nutritional formula specially developed for chronic kidney disease patients on protein-restricted diets: a randomized controlled trial

“…A carbon adsorbent known to reduce serum indoxyl sulfate prevented CKD progression in a small study [25]. However, in the recent Evaluating Prevention of Progression in CKD (EPPIC) study, the carbon adsorbent was not effective in preventing CKD progression [26]. Further study is required to confirm whether indoxyl sulfate is related to kidney dysfunction and CKD progression.…”

Drugs for Diabetic Nephropathy- Full Review

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