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 effectiveness of a large molecular weight glucose polymer fraction (Icodextrin) as a novel ''colloid'' osmotic agent in peritoneal dialysis was established, but the long-term safety remained undetermined. A randomized, controlled multicenter investigation of Icodextrin in ambulatory peritoneal dialysis (MIDAS) was undertaken to evaluate the long-term safety and efficacy by comparing daily overnight (8 to 12 hr dwell) use of isosmolar Icodextrin (282 mOsm/kg) with conventional 1.36% (346 mOsm/kg) and 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 patients were divided into weak (1.36%) or strong (3.86%) subgroups based on their use of glucose solutions overnight during the pretreatment baseline 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 +257 to +497 ml; P < 0.0001] and 5.5 times greater at 12 hours (561 +/- 44 vs. 101 +/- 48 ml, 95% CI for the difference +329 to +590; P < 0.0001) 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 difference -47 to +325 ml; P = 0.06). The biochemical profiles were no different in the two groups except for a small fall in serum sodium (140 to 136 mmol/liter) and chloride (103 to 99 mmol/liter) concentrations 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/liter 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 study demonstrates that the daily overnight use of an isosmolar Icodextrin solution was safe and effective up to six months and could replace the overnight use of hyperosmolar glucose solutions. Longer term data will be necessary to establish further safety and efficacy.