CTST-21: A Phase 2, Randomized, Double-Blind, Multi-Center Study Comparing 15G Cross-Linked Polyelectrolyte (CLP) versus Placebo in Heart Failure Patients with Chronic Kidney Disease

The goal of this double-blind, randomized, placebo-controlled trial was to evaluate the effects of a cross-linked polyelectrolyte (CLP) on serum potassium and measures of congestion in patients with heart failure (HF) and chronic kidney disease (CKD). The pre-specified primary endpoint was change in serumK+ over time, with an associated goal of facilitating the initiation of aldosterone blockers in patients at risk for hyperkalemia. Since CLP also removes fluid through the GI tract, we also hypothesized that this intervention would ameliorate congestion as assessed by serial weights and its associated symptoms, as assessed by NYHA class, quality of life (assessed by the KansasCityCardiomyopathyQuestionnaire (KCCQ), and 6minutewalk test (6MWT) after 8 weeks of CLP treatment. Results: 111 patients (mean age 69; 59% men) were randomized to CLP or placebo. Unexpectedly, CLP did not have a significant effect on serum K+, and there was no significant difference in the number of patients who could be titrated to a 50 mg spironolactone dose. However, as shown in Figure 1 below, weight loss was significantly greater in the CLP group at week 1 (-0,716 1.5 vs. -0.11 6 2.0 Kg, p50.014, and week 2 (-0.83 6 1.8 kg vs. -0.29 6 2.3 kg, p50.004). In addition, the proportion of subjects with marked or disabling dyspnea on exertion was lower in the CLP group and this difference increased over time (Figure 2). A highly significant (p50.005) improvement in the KCCQ was also observed after 4 weeks of treatment in the CLP group, with a somewhat lesser change at week 8. Safety evaluation: CLP was generally well tolerated, with 21 active patients and 16 placebo patients reporting adverse events, the majority of which were gastrointesFigure 1. Change in weight. tinal (abdominal discomfort (7 vs. 2), distension (3 vs. 1) or nausea (3 vs. 0). There were 4 deaths, all of which were in the CLP group. One occurred at Week 3 in a 70 year old man with NYHA class IV ischemic heart failure (LVEF520%). The second occurred at Week 4 in a 60 year old diabetic man with NYHA class III ischemic heart failure (LVEF 520%). The third death occurred at Week 6 in a 63 year old man with ischemic HF, worsening fluid retention, and progressive CKD. The fourth death Figure 2. Improvement in dyspnea. Figure 3. Improvement in KCCQ. SAEs (Events/Patient Year) Selected Adverse Events CircuLite (n514)*