IMPENDIA- PEN VS Dianeal Only Improved Metabolic Control In Diabetic CAPD and APD Patients

• Dianeal (Drug): Dianeal 1.5% Dextrose (1.38% Glucose), 2.5% Dextrose (2.27% Glucose), 4.25% Dextrose (3.86% Glucose)
• Physioneal (Drug): Physioneal 40 or Physioneal 35
• Extraneal (Drug): Extraneal - 7.5% Icodextrin
• Nutrineal (Drug): Nutrineal - 1.1% Amino Acids

Primary outcomes

• Change From the Baseline Value in HbA1c at Month 3 and 6 [Baseline, Month 3, Month 6 (End of Study)]: HbA1c is a specific glycohemoglobin, and adduct of glucose attached to the beta-chain terminal valine residue. Measured using a Tina-quant immunological assay suitable for samples from end stage renal disease (ESRD) patients and with icodextrin metabolites or equivalent. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0.

Secondary outcomes

• Change From Baseline in Glycemic Control Medication Usage at Month 3 and 6 [Baseline, Month 3, Month 6 (End of Study)]: This data used diabetic prescription drug information from insulin and oral glycemic control concomitant medications reported. Glycemic control medications classes allowed were limited to insulin, sulfonylureas, and thiazolidinediones. Subjects were provided with a paper diary on which they recorded doses of all glycemic control medications taken for 1 day prior to the Screening visit and for 8 days prior to the study visits at Month 3 and Month 6. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0.
• Number of Severe Hypoglycemic Event Requiring Medical Intervention [Baseline through Month 6 (End of Study)]: Severe hypoglycemia is defined by DCCT (Diabetes Control and Complications Trial) as any episode requiring external assistance to aid recovery or resulted in seizures or coma and included, as part of the definition, that the subject's blood glucose concentration had to have been documented as < 50mg/dL (<2.8mmol/L) for hypoglycemia, and/or the clinical manifestations had to have been reversed with oral carbohydrate, intramuscular glucagon, or intravenous glucose. Descriptive statistics were done, no inferential statistical analyses were performed.
• Change From Baseline of Metabolic Control Determined by Lipid Profile and Triglycerides at Month 3 and 6 [Baseline, Month 3, Month 6 (End of Study)]: Values for Total Cholesterol (TC), Low Density Lipoprotein Cholesterol (LDLC), High Density Lipoprotein Cholesterol (HDLC), Very Low Density Lipoprotein (VLDL), and Triglycerides are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0.
• Change From Baseline of Metabolic Control Determined by Lipoproteins at Month 3 and 6 [Baseline, Month 3, Month 6 (End of Study)]: Values for Lipoprotein A (Lp(a)), Apolipoprotein A1 (Apo A1), and Apolipoprotein B (Apo B) are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0.
• Change From Baseline of Metabolic Control Determined by Insulin Action of Insulin and C-peptide at Month 3 and 6 [Baseline, Month 3, Month 6 (End of Study)]: Values for Insulin and C-peptide are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0.
• Change From Baseline of Metabolic Control Determined by Insulin Action of Pro-Insulin at Month 3 and 6 [Baseline, Month 3, Month 6 (End of Study)]: Values for Pro-Insulin are provided. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0.
• Number of Participants by Change From Baseline Score in Subjective Global Assessment (SGA) Class at Month 6 [Baseline and Month 6 (End of Study)]: Nutritional Status by SGA include the following: (a) Weight change over 6 months, (b) dietary history of food intake over the previous 24-hour period with a determination by the subject as to whether this was a typical or atypical diet for the subject, (c) significant and sustained gastrointestinal distress, (d) functional status, (e) metabolic stress including frequent infections, fever, peritonitis, uncontrolled diabetes and active inflammatory bowel disease. The SGA used a 7-point scale, where a decrease score in the change from baseline shows signs of increased malnourishment, and an increased score (e.g., +2) is improved nourishment. Scale: 6 - 7 = very mild risk to well-nourished; 3 - 5 = no clear sign of normal status or severe malnutrition; 1 - 2 = severely malnourished
• Change From Baseline of Nutritional Status Determined by Albumin and Total Protein (Labs) at Month 3 and 6 [Baseline, Month 3, Month 6 (End of Study)]: Values for Albumin and Total Protein are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0.
• Change From Baseline of Nutritional Status Determined by PNA and nPNA (Labs) at Month 3 and 6 [Baseline, Month 3, Month 6 (End of Study)]: Values for Protein Nitrogen Appearance (PNA) and normalized protein nitrogen appearance (nPRNA) are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0.
• Change From Baseline of Nutritional Status Determined by Pre-albumin (Labs) at Month 3 and 6 [Baseline, Month 3, Month 6 (End of Study)]: Values for Pre-albumin are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0.
• Change From Baseline of Nutritional Status Determined by Drained Body Weight at Month 3 and 6 [Baseline, Month 3, Month 6 (End of Study)]: Values for Drained Body Weight are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0.
• Change From Baseline of Nutritional Status Determined by Body Mass Index (BMI) at Month 3 and 6 [Baseline, Month 3, Month 6 (End of Study)]: Values for BMI are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0.
• Change From Baseline of Nutritional Status Determined by Waist Circumference at Month 6 [Baseline, Month 6 (End of Study)]: Values for Waist Circumference are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0.
• Change From Baseline of Nutritional Status Determined by Protein and Calories at Month 3 and 6 [Baseline, Month 3, Month 6 (End of Study)]: Values for Protein and Calories are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0.
• Change From Baseline in QOL Based pm the EQ 5D Questionnaire Index at Month 3 and 6 [Baseline, Month 3, Month 6 (End of Study)]: European Quality of Life, 5 Dimensions (EQ-5D) generates a single index score based on a descriptive system that defines health in terms of 5 dimensions, consisting of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The possible range for each dimension is 1 to 3, where 1=no problems, 2=moderate problems, 3=extreme problems. Higher score implies more problems (worsening). According to this classification, 243 potential health states are defined. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0.
• Change From Baseline in QOL Based on the EQ 5D Quest Health Status at Month 3 and 6 [Baseline, Month 3, Month 6 (End of Study)]: Visual analogue scale to generate a self-perceived rating of health status. Visual analogue scale is the second part of the questionnaire, asking to mark health status on the day of the interview on a 20 cm vertical scale with end points of 0 and 100. There are notes at the both ends of the scale that the bottom rate (0) corresponds to " the worst health you can imagine", and the highest rate (100) corresponds to "the best health you can imagine". Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0.
• Change From Baseline in QOL Based on the Diabetes Symptom Checklist (DSC) at Month 3 and 6 [Baseline, Month 3, Month 6 (End of Study)]: The Diabetes Symptoms Checklist was designed to assess the presence and perceived burden of diabetes-related symptoms. Respondents were to consider troublesomeness of 34 symptoms on a 5-point scale ranging from 5="extremely" to 1="not at all." For symptoms/side-effects not experienced, the item was scored as 0. Symptoms were grouped into the following subscales: psychological fatigue, psychological cognitive, neurology pain, neurology sensory, cardiology, ophthalmology, hypoglycemia, hyperglycemia. Subscale scores were calculated as the sum of the given subscale divided by the total number of items in the scale. Total score was computed from the sum of the 8 subscales and ranged from 0 to 40. Higher scores indicate greater symptom burden. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0.
• Change From Baseline of MRI Body Composition at Month 6 [Baseline, Month 6 (End of Study)]: Values for Abdominal Subcutaneous Fat Volume and Abdominal Visceral Fat Volume are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0.
• Change From Baseline of Left Ventricular (LV) End Diastolic and Systolic Volume as Determined by MRI at Month 6 [Baseline, Month 6 (End of Study)]: Values for Left Ventricular (LV) End Diastolic and Systolic Volume are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0.
• Change From Baseline of Left Ventricular (LV) Mass Without and With Pap Muscles as Determined by MRI at Month 6 [Baseline, Month 6 (End of Study)]: Values for Left Ventricular (LV) Mass Without and With Pap Muscles are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0.
• Change From Baseline of Left Ventricular (LV) Ejection Fraction as Determined by MRI at Month 6 [Baseline, Month 6 (End of Study)]: Values for Left Ventricular (LV) Ejection Fraction are included. Statistical analysis includes estimates of Least Squares (LS) comparing differences between treatment groups by visit and p-value using analysis of covariance (ANOVA) testing that the differences=0.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. M/F patients 18 years of age or older
2. Diagnosis of ESRD (GFR ≤ 15 mL/min)
3. CAPD or APD using only Dianeal and/or Physioneal, at least 1 exchange of 2.5% or 4.25% dextrose/day, no prescribed dry time
4. DM (Type 1 and 2) on glycemic-control medication, for 90 days
5. HbA1c > 6.0% but ≤ 12.0%
6. Blood hemoglobin ≥ 8.0 g/dL, but ≤ 13.0 g/dL

Exclusion Criteria:

1. Cardiovascular event within the last 90 days
2. Ongoing clinically significant congestive heart failure (NYHA class III or IV)
3. Allergy to starch-based polymers
4. Glycogen storage disease
5. Glycogen storage disease
6. Peritonitis, exit-site or tunnel infection treated with antibiotics within last 30 days
7. Mean Arterial Pressure (MAP) ≥ 125 mm Hg, or volume depleted (MAP < 77) at Screening.
8. Serum urea > 30 mmol/L
9. Receiving rosiglitazone maleate

Participant flow

Outcome results

• Change From the Baseline Value in HbA1c at Month 3 and 6 (Primary), Mean, Percent Change: Non-Glucose Sparing Prescriptions 0.2 +/- 1.1; Glucose Sparing Prescriptions -0.6 +/- 1.3 (p <0.001)
• Change From Baseline in Glycemic Control Medication Usage at Month 3 and 6 (Secondary), Mean, Percent Change: Non-Glucose Sparing Prescriptions 3.5 +/- 21.2; Glucose Sparing Prescriptions -3.3 +/- 16.4 (p 0.312)
• Number of Severe Hypoglycemic Event Requiring Medical Intervention (Secondary), Number, events: Non-Glucose Sparing Prescriptions 1; Glucose Sparing Prescriptions 3
• Change From Baseline of Metabolic Control Determined by Lipid Profile and Triglycerides at Month 3 and 6 (Secondary), Mean, mmol/L: Non-Glucose Sparing Prescriptions 0.1 +/- 1.1; Glucose Sparing Prescriptions -0.5 +/- 1.2 (p 0.010)
• Change From Baseline of Metabolic Control Determined by Lipoproteins at Month 3 and 6 (Secondary), Mean, mg/dL: Non-Glucose Sparing Prescriptions 2.3 +/- 8.9; Glucose Sparing Prescriptions 3.3 +/- 9.8 (p 0.485)
• Change From Baseline of Metabolic Control Determined by Insulin Action of Insulin and C-peptide at Month 3 and 6 (Secondary), Mean, pg/mL: Non-Glucose Sparing Prescriptions 70.3 +/- 514.2; Glucose Sparing Prescriptions 69.4 +/- 809.4 (p 0.655)
• Change From Baseline of Metabolic Control Determined by Insulin Action of Pro-Insulin at Month 3 and 6 (Secondary), Mean, pmol/L: Non-Glucose Sparing Prescriptions -1.8 +/- 19.6; Glucose Sparing Prescriptions 13 +/- 71.3 (p 0.721)
• Number of Participants by Change From Baseline Score in Subjective Global Assessment (SGA) Class at Month 6 (Secondary), Number, participants: Non-Glucose Sparing Prescriptions 1; Glucose Sparing Prescriptions 2 (p 0.624)
• Change From Baseline of Nutritional Status Determined by Albumin and Total Protein (Labs) at Month 3 and 6 (Secondary), Mean, g/L: Non-Glucose Sparing Prescriptions -0.1 +/- 3.1; Glucose Sparing Prescriptions -0.6 +/- 3.6 (p 0.338)
• Change From Baseline of Nutritional Status Determined by PNA and nPNA (Labs) at Month 3 and 6 (Secondary), Mean, g/kg/day: Non-Glucose Sparing Prescriptions -0.8 +/- 14.1; Glucose Sparing Prescriptions 12.8 +/- 14.4 (p 0.127)
• Change From Baseline of Nutritional Status Determined by Pre-albumin (Labs) at Month 3 and 6 (Secondary), Mean, mg/dL: Non-Glucose Sparing Prescriptions 0.4 +/- 7.2; Glucose Sparing Prescriptions -1.9 +/- 5.5 (p 0.019)
• Change From Baseline of Nutritional Status Determined by Drained Body Weight at Month 3 and 6 (Secondary), Mean, kg: Non-Glucose Sparing Prescriptions -0.2 +/- 4.5; Glucose Sparing Prescriptions -0.2 +/- 3.5 (p 0.884)
• Change From Baseline of Nutritional Status Determined by Body Mass Index (BMI) at Month 3 and 6 (Secondary), Mean, kg/m2: Non-Glucose Sparing Prescriptions -0.1 +/- 1.5; Glucose Sparing Prescriptions -0.1 +/- 1.3 (p 0.961)
• Change From Baseline of Nutritional Status Determined by Waist Circumference at Month 6 (Secondary), Mean, cm: Non-Glucose Sparing Prescriptions 0 +/- 6.4; Glucose Sparing Prescriptions 0.4 +/- 5.9 (p 0.871)
• Change From Baseline of Nutritional Status Determined by Protein and Calories at Month 3 and 6 (Secondary), Mean, grams: Non-Glucose Sparing Prescriptions -5.6 +/- 14.1; Glucose Sparing Prescriptions -4.9 +/- 45.3 (p 0.608)
• Change From Baseline in QOL Based pm the EQ 5D Questionnaire Index at Month 3 and 6 (Secondary), Mean, Percent Change: Non-Glucose Sparing Prescriptions -0.01 +/- 0.18; Glucose Sparing Prescriptions -0.04 +/- 0.19 (p 0.412)
• Change From Baseline in QOL Based on the EQ 5D Quest Health Status at Month 3 and 6 (Secondary), Mean, Score on a Scale: Non-Glucose Sparing Prescriptions -2.33 +/- 23.37; Glucose Sparing Prescriptions -2.58 +/- 27.14 (p 0.525)
• Change From Baseline in QOL Based on the Diabetes Symptom Checklist (DSC) at Month 3 and 6 (Secondary), Mean, Scores on a scale: Non-Glucose Sparing Prescriptions 2.34 +/- 20.73; Glucose Sparing Prescriptions 2.39 +/- 20.33 (p 0.526)
• Change From Baseline of MRI Body Composition at Month 6 (Secondary), Mean, mL: Non-Glucose Sparing Prescriptions -49 +/- 81.7; Glucose Sparing Prescriptions -64.8 +/- 73.2 (p 0.495)
• Change From Baseline of Left Ventricular (LV) End Diastolic and Systolic Volume as Determined by MRI at Month 6 (Secondary), Mean, mL: Non-Glucose Sparing Prescriptions 2.1 +/- 35.5; Glucose Sparing Prescriptions 0.7 +/- 28.4 (p 0.626)
• 2 more outcome measures not shown.

Adverse events

Serious adverse events by term

47 more terms not shown.

Other adverse events by term

257 more terms not shown.

Limitations and caveats: This is a pooled analysis of NCT00567489, NCT00567398, and NCT01219959. Given that the glucose content of the PD solutions were similar, the pooling of the results were considered a valid method to answer the underlying research questions.

• Gokal R. Taking peritoneal dialysis beyond the year 2000. Perit Dial Int. 1999;19 Suppl 3:S35-42; discussion S43. PMID 10433550
• Delarue J, Maingourd C, Couet C, Vidal S, Bagros P, Lamisse F. Effects of oral glucose on intermediary metabolism in continuous ambulatory peritoneal dialysis patients versus healthy subjects. Perit Dial Int. 1998 Sep-Oct;18(5):505-11. PMID 9848629
• Holmes CJ, Shockley TR. Strategies to reduce glucose exposure in peritoneal dialysis patients. Perit Dial Int. 2000;20 Suppl 2:S37-41. PMID 10911641
• Furuya R, Odamaki M, Kumagai H, Hishida A. Beneficial effects of icodextrin on plasma level of adipocytokines in peritoneal dialysis patients. Nephrol Dial Transplant. 2006 Feb;21(2):494-8. doi: 10.1093/ndt/gfi197. Epub 2005 Oct 12. PMID 16221697
• Nundy S, Baron JH. The use of neutral red as a peroperative test of vagal innervation. Scand J Gastroenterol. 1975;10(8):847-50. PMID 1202618
• Martikainen T, Teppo AM, Gronhagen-Riska C, Ekstrand A. Benefit of glucose-free dialysis solutions on glucose and lipid metabolism in peritoneal dialysis patients. Blood Purif. 2005;23(4):303-10. doi: 10.1159/000086553. Epub 2005 Jun 23. PMID 15980620