Study to Evaluate the Effects Icodextrin Versus Dianeal on Insulin Resistance in Nondiabetic Automated Peritoneal Dialysis Patients (STARCH)

Study to Evaluate the Effects Icodextrin Versus Dianeal on Insulin Resistance in Nondiabetic Automated Peritoneal Dialysis Patients

A Study to Evaluate the Effects of Icodextrin vs 2.5% Dianeal Used for the Long Dwell in Apd: a Randomized, Open-label Clinical Trial to Analyse the Insulin Resistance Using the Homa Index in Prevalent, Non-diabetic Patients

LOCATION OF STUDY: Multicentric study in Brazil. PURPOSE OF THE STUDY: To measure changes in HOMA index when non-diabetic patients in APD were exposed to 7,5% Icodextrin for the long-dwell; and to compare such changes with those produced by 2,5% glucose for the long-dwell. PRIMARY OUTCOME: The primary efficacy outcome was to measure HOMA index to set the differences with regard to baseline values of this variable for the two groups as well as in each group, which showed control of the glucose metabolism. STAGE OF THE STUDY : Phase IV postmarket study DESIGN: Randomized, open-label, multicenter study. Patients were randomized to receive either to Extraneal (7,5% Icodextrin) or 2.5% Dianeal during the long-dwell. SAMPLE SIZE: Randomization Upon completion of the study TOTAL: 120 60 ExtranealTM 60 30 Dianeal® 60 30 Duration: 1 year.

1. SUMMARY OF THE STUDY 1.1 PROTOCOLE TITLE : A RANDOMIZED, OPEN-LABEL CLINICAL TRIAL TO EVALUATE THE EFFECTS OF ICODEXTRIN Vs 2,5% DIANEAL USED FOR THE LONG-DWELL ON HOMA INDEX IN PREVALENT, NON-DIABETIC, PATIENTS IN AUTOMATED PERITONEAL DIALYSIS (APD) 1.2 MAIN RESEARCHERS: Roberto Pecoits Filho, Thyago P. Moraes 1.3 LOCATION OF STUDY: Multicentric study in Brazil. 1.4 PURPOSE OF THE STUDY: To measure changes in HOMA index when non-diabetic patients in APD were exposed to 7,5% Icodextrin for the long-dwell; and to compare such changes with those produced by 2,5% glucose for the long-dwell. 1.5 PRIMARY OUTCOME: The primary efficacy outcome was to measure HOMA index to set the differences with regard to baseline values of this variable for the two groups as well as in each group, which showed control of the glucose metabolism. 1.6 SECONDARY OUTCOMES: 1.6.1 Other efficacy outcomes were total UF, long-dwell UF, and preprandial glycemia (taken first in the morning before breakfast), serum insulin levels and glycated haemoglobin. 1.6.2 The incidence of adverse events will be measured as a safety outcome. 1.7 STAGE OF THE STUDY : Phase IV postmarket study 1.8 DESIGN: Randomized, open-label, multicenter study. Patients were randomized to receive either to Extraneal (7,5% Icodextrin) or 2.5% Dianeal during the long-dwell. 1.9 SAMPLE SIZE: Randomization Upon completion of the study TOTAL: 100 60 ExtranealTM 50 30 Dianeal® 50 30 1.12 PHARMACEUTICAL FORM, ROUTE OF DE ADMINISTRATION AND DOSAGE ExtranealTM (7.5% Icodextrin) solution for Peritoneal Dialysis: It is labelled as "solution for dialysis" to be administered within the study for a period of one (1) year. Available in 2 liter bags of peritoneal dialysis solution (Twin Bag) for CAPD, this product will be used during the long-dwell. Dianeal® PD4 (2.5% Dextrose) solution for Peritoneal Dialysis: It is labelled as 2.27% glucose-based "solution for dialysis", to be administered within the study for a period of one (1) year. Available in 2 and 2.5 liter bags of peritoneal dialysis solution (Twin Bag) for CAPD, this product will be used during the long-dwell. Duration: 1 year.

Adjusted HOMA Index Score at 3 Months Using Baseline Values as a Covariate and Groups as the Fixed Factor

Adjusted HOMA index score at 3 months using baseline values as a covariate and groups as the fixed factor. HOMA index was calculated as follows: (fasting glucose(mg/dl) x fasting serum insulin (μU/mL))/405

Serum glucose measured in oral fasting but not peritoneal fasting. For this outcome we compared groups using analysis of covariance (ANCOVA) using the baseline values as covariate, groups as the fixed factor and the value obtained at 90 days as the dependent variable. Significance level for alpha was setting at < 0.05.

Serum insulin was log-transformed to meet all criteria for ANCOVA. The baseline value was treated as covariate, groups as the fixed factor and the serum insulin at 3 months as the dependent variable. Serum insulin was measured in oral fasting by chemioluminescense.

Adjusted glycated hemoglobin was obtained and compared between groups using analysis of covariance (ANCOVA). The baseline values of HbA1c was used as covariate, the groups as the fixed factor and the value obtained at 90 days as the dependent variable. Glycated hemoglobin was measured by high-performance liquid chromatography.

Total ultrafiltration obtained in 24 hours was obtained and compared between groups using analysis of covariance (ANCOVA). The baseline values of total ultrafiltration was used as covariate, the groups as the fixed factor and the value obtained at 90 days as the dependent variable.

Inclusion Criteria: 1.10.1 Older than 18 years old. High PET value, average-high or average-low. Cause of renal chronic disease other than diabetes mellitus. Patient in APD Prevalent patient in APD (defined as at least 90 total days of dialysis therapy) Exclusion Criteria: Not willing to participate. A Charlson comorbidity index >7, or a life expectancy < 12 months as assessed by the treating physician. Positive VIH. Episodes of peritonitis during the month preceding the randomization. Significant cardiovascular, metabolic or infectious complications during the month preceding the randomization. Patients with active cancer. Patients with known allergies to corn starch polymers. Patients who are unable to provide an informed consent because of significant psychiatric disorder or mental illness Patients not meeting adequacy goals several months after the change in the dosage regime.