A RANDOMIZED MULTICENTER CLINICAL-TRIAL COMPARING ISOSMOLAR ICODEXTRIN WITH HYPEROSMOLAR GLUCOSE SOLUTIONS IN CAPD

A randomized multicenter clinical trial comparing isosmolar Icodextrin with hyperosmolar glucose solutions in CAPD. The osmotic effectivenes s of a large molecular weight glucose polymer fraction (Icodextrin) as a novel ''colloid'' osmotic agent in peritoneal dialysis was establis hed, but the long-term safety remained undetermined. A randomized, con trolled multicenter investigation of Icodextrin in ambulatory peritone al dialysis (MIDAS) was undertaken to evaluate the long-term safety an d efficacy by comparing daily overnight (8 to 12 hr dwell) use of isos molar Icodextrin (282 mOsm/kg) with conventional 1.36% (346 mOsm/kg) a nd 3.86% (484 mOsm/kg) glucose exchanges over six months. Two hundred and nine patients were randomized from 11 centers, with 106 allocated to receive Icodextrin (D) and 103 to remain on glucose (control group; C); 138 patients completed the six month study (71 C, 67 D). All pati ents were divided into weak (1.36%) or strong (3.86%) subgroups based on their use of glucose solutions overnight during the pretreatment ba seline period. The mean (+/- SEM) overnight ultrafiltration (UF) with D was 3.5 times greater than 1.36% glucose at eight hours [527 +/- 36 vs. 150 +/- 47 ml; 95% confidence interval (CI) for the difference +25 7 to +497 ml; P < 0.0001] and 5.5 times greater at 12 hours (561 +/- 4 4 vs. 101 +/- 48 ml, 95% CI for the difference +329 to +590; P < 0.000 1) and no different from that of 3.86% glucose at eight hours (510 +/- 48 vs. 448 +/- 60 ml, 95% CI for the difference -102 to +226 ml; P = 0.44) and at 12 hours (552 +/- 44 vs. 414 +/- 78 ml, 95% CI for the di fference -47 to +325 ml; P = 0.06). The biochemical profiles were no d ifferent in the two groups except for a small fall in serum sodium (14 0 to 136 mmol/liter) and chloride (103 to 99 mmol/liter) concentration s in the Icodextrin group. The mean serum maltose increased from a pre -dialysis value of 0.04 g/liter to a steady state level of 1.20 g/lite r within two weeks and remained stable throughout the study. This was not associated with any adverse clinical effects and the overall CAPD- related symptom score was significantly better for D than C. This stud y demonstrates that the daily overnight use of an isosmolar Icodextrin solution was safe and effective up to six months and could replace th e overnight use of hyperosmolar glucose solutions. Longer term data wi ll be necessary to establish further safety and efficacy.