Clinical trial NCT01632046: Administration of pH-Neutral Peritoneal Dialysis Solutions Containing Lactate or Bicarbonate in Children
Official title: Randomized, Long-Term Administration of pH-Neutral PD Solutions Containing Lactate (BALANCE) or Bicarbonate (BICAVERA) in Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Renal Failure
Peritoneal Membrane Disorder
Keywords: peritoneal dialysis
bicarbonate/lactate buffer
peritoneal transport capacity
ultrafiltration
children
Lead sponsor: Heidelberg University
Sponsor class: OTHER
First posted: 2012-06-29
Enrollment: 42
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Evaluation of the effect of a lactate based and a bicarbonate based double-chambered, pH-neutral PD solution on peritoneal transport capacity in children.
timeFrame: 2 months run in 10 months study period
Secondary outcomes:
measure: Ultrafiltration
timeFrame: 2 months run in 10 months observation
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: University Children's Hospital
city: Helsinki
country: Finland
facility: University Children's Hospital
city: Strasbourg
country: France
facility: University Children's Hospital
city: Essen
country: Germany
facility: University Children's Hospital
city: Hamburg
country: Germany
facility: University Children´s Hospital
city: Jena
country: Germany
facility: University Children's Hospital
city: Milan
country: Italy
facility: University Children's Hospital
Study officials:
affiliation: University of Heidelberg, Center for Pediatric and Adolescent Medicine
name: Claus P Schmitt, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.