Administration of pH-Neutral Peritoneal Dialysis Solutions Containing Lactate or Bicarbonate in Children

NCT ID: NCT01632046

Last Updated: 2012-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-03-31
• Study Completion Date: 2007-03-31

Brief Summary

Peritoneal Dialysis (PD) is the preferred treatment modality in children with end-stage renal disease. Unfortunately progressive alterations of the peritoneal membrane occur with time on PD, leading to a continuous loss of peritoneal transport function. Recently, double-chambered PD solutions with less Glucose Degradation Products (GDPs) and neutral pH have been approved for the European market. Short term administration suggests comparable clearance rates compared with conventional solutions. In vitro studies demonstrate an improved local immune defense system. To compensate for metabolic acidosis, the available solutions either contain lactate or bicarbonate, the impact of either buffer on long term acidosis control and peritoneal membrane integrity, however, is unknown.

The prospective, European multi-center study will provide the first long term administration of pH neutral, low GDP solutions in children. 60 children will randomly be treated with a bicarbonate (BicaVera) and a lactate based solution (Balance), respectively. The primary end point will be the effect of either PD-solution on peritoneal transport characteristics (D/P Creatinine). Secondary end-points will be the effects on ultrafiltration capacity, acid-base balance, peritoneal morphology, incidence and severity of peritonitis, and on surrogate parameters of biocompatibility and carbonyl stress. Moreover, potential genetic determinants of the peritoneal transporter status and of the continued morphological transformation of the peritoneum will be assessed.

After a 2 month run-in period, using a conventional, acidic, single-chambered PD-solution, the patients will be randomized to a 10 month study period using BicaVera and Balance, respectively. Dialysis regime and follow up in the out-patient clinic will be performed according to clinical needs (every 4 weeks); episodes of peritonitis will be treated according to international guidelines. Bicarbonate supplements will be prescribed at a dose of 0.5 mmol/kg *d, if blood bicarbonate levels fall below 17 mmol/l. PD adequacy will be verified by routine, monthly venous blood sampling and a capillary blood gas analysis. 2-5 ml of blood will be drawn for analysis of relevant gene polymorphisms. At study entry, after 3, 6 and 10 months, a 24h dialysate- and urine collection, a peritoneal equilibration test an intraperitoneal pressure measurement will be performed. Peritoneal biopsies will be obtained at any time of abdominal surgery. Adverse events will be screened meticulously. The trial will be carried out in accordance with the German medicines act (AMG) and other local requirements, with particular reference to the ICH guidelines for Good Clinical Practice, and the declaration of Helsinki. At study end, the patients will decide together with the responsible physician which PD-fluid should be used further one.

Detailed Description

For details please see Nau B, Schmitt CP et al; BMC Nephrol. 2004 Oct 14;5:14.

Conditions

Chronic Renal Failure; Peritoneal Membrane Disorder

Keywords

peritoneal dialysis; bicarbonate/lactate buffer; peritoneal transport capacity; ultrafiltration; children

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BicaVera, dialysis

Two Parallel arms. If patient randomised to the BicaVera arm he will be dialysed with bicarbonate based PD fluid (BicaVera) for 10 months. Dialysis prescription is determined according to clinical needs, dialysate glucose concentrations are 1.5, 2.3 and 4.25 %.

Group Type: ACTIVE_COMPARATOR

lactate and bicarbonate buffered dialysis solutions

Intervention Type: DRUG

Either PD-solution will be applied. Number of cycles and glucose concentration will be varied according to clinical needs. Sleep Safe system will be used and connected to Sleep Safe Cyclers in patient on CCPD.

Balance, dialysis

If patient is randomised to the Balance arm, he will be dialysed with lactate based PD fluid (Balance) for 10 months. Dialysis prescription is determined according to clinical needs, dialysate glucose concentrations are 1.5, 2.3 and 4.25 %.

Group Type: ACTIVE_COMPARATOR

lactate and bicarbonate buffered dialysis solutions

Intervention Type: DRUG

Either PD-solution will be applied. Number of cycles and glucose concentration will be varied according to clinical needs. Sleep Safe system will be used and connected to Sleep Safe Cyclers in patient on CCPD.

Interventions

lactate and bicarbonate buffered dialysis solutions

Either PD-solution will be applied. Number of cycles and glucose concentration will be varied according to clinical needs. Sleep Safe system will be used and connected to Sleep Safe Cyclers in patient on CCPD.

Intervention Type: DRUG

Other Intervention Names

BicaVera; Balance

Eligibility Criteria

Inclusion Criteria

• Male and female patients, 1 months to 21 years of age (newborns excluded)
• CAPD or CCPD for end stage renal disease
• Dwell volume ~ 1100ml/m² body surface area
• Last peritonitis at least 3 weeks ago
• Written informed consent

Exclusion Criteria

• Reduced efficiency of peritoneal dialysis due to anatomic anomalies or intraperitoneal adhesions
• Uncontrolled hyperphosphatemia
• Participation in a clinical trial with an investigational drug within one month prior start of study. Prior participation in this trial
• Suspicion of drug abuse
• Severe pulmonary, cardiac or hepatic disease/insufficiency
• Any kind of malignancy

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Heidelberg University

OTHER

Sponsor Role: lead

Responsible Party

Claus Peter Schmitt

M.D.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Claus P Schmitt, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Heidelberg, Center for Pediatric and Adolescent Medicine

Locations

University Children's Hospital

Vienna, , Austria

University Children's Hospital

Helsinki, , Finland

University Children's Hospital

Strasbourg, , France

University Children's Hospital

Essen, , Germany

University Children´s Hospital

Hamburg, , Germany

University Children's Hospital

Jena, , Germany

University Children's Hospital

Milan, , Italy

Countries

Austria; Finland; France; Germany; Italy

References

Nau B, Schmitt CP, Almeida M, Arbeiter K, Ardissino G, Bonzel KE, Edefonti A, Fischbach M, Haluany K, Misselwitz J, Kemper MJ, Ronnholm K, Wygoda S, Schaefer F; European Pediatric Peritoneal Dialysis Study Group. BIOKID: randomized controlled trial comparing bicarbonate and lactate buffer in biocompatible peritoneal dialysis solutions in children [ISRCTN81137991]. BMC Nephrol. 2004 Oct 14;5:14. doi: 10.1186/1471-2369-5-14.

Reference Type: BACKGROUND

PMID: 15485574 (View on PubMed)

Schmitt CP, Nau B, Gemulla G, Bonzel KE, Holtta T, Testa S, Fischbach M, John U, Kemper MJ, Sander A, Arbeiter K, Schaefer F. Effect of the dialysis fluid buffer on peritoneal membrane function in children. Clin J Am Soc Nephrol. 2013 Jan;8(1):108-15. doi: 10.2215/CJN.00690112. Epub 2012 Nov 2.

Reference Type: DERIVED

PMID: 23124784 (View on PubMed)

Other Identifiers

University of Heidelberg

Identifier Type: OTHER

Identifier Source: secondary_id

BIOKID 04 EU

Identifier Type: -

Identifier Source: org_study_id