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

Chronic Renal Failure Clinical Trial

— BIOKID  

Official title:

Randomized, Long-Term Administration of pH-Neutral PD Solutions Containing Lactate (BALANCE) or Bicarbonate (BICAVERA) in Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01632046
• Other study ID #: BIOKID 04 EU
• Secondary ID: University of He
• Status: Completed
• Phase: Phase 4
• First received: June 28, 2012
• Last updated: June 28, 2012
• Start date: March 2004
• Est. completion date: March 2007

Study information

• Verified date: June 2012
• Source: Heidelberg University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: March 2007
• Est. primary completion date: March 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Month to 21 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Renal Failure
• Kidney Failure, Chronic
• Peritoneal Diseases
• Peritoneal Membrane Disorder

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Austria	University Children's Hospital	Vienna
Finland	University Children's Hospital	Helsinki
France	University Children's Hospital	Strasbourg
Germany	University Children's Hospital	Essen
Germany	University Children´s Hospital	Hamburg
Germany	University Children's Hospital	Jena
Italy	University Children`s Hospital	Milan

Sponsors (1)

Lead Sponsor	Collaborator
Heidelberg University

Countries where clinical trial is conducted

Austria,  Finland,  France,  Germany,  Italy, 

References & Publications (1)

Nau B, Schmitt CP, Almeida M, Arbeiter K, Ardissino G, Bonzel KE, Edefonti A, Fischbach M, Haluany K, Misselwitz J, Kemper MJ, Rönnholm 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of the effect of a lactate based and a bicarbonate based double-chambered, pH-neutral PD solution on peritoneal transport capacity in children.	Following a two months run in period patients are randomized to either lactate or bicarbonate buffered PD solution. The primary outcome measure is dialysate over plasma creatinine as a measure of peritoneral transport efficacy. It will be determined at 0, 3, 6 and 10 months.	2 months run in 10 months study period	No
Secondary	Ultrafiltration	The ultrafiltration is recorded daily by the caretakers, mean weakly ultrafiltration will be analysed. (Further outcome measures include the effect of either PD solution on acid-base balance, incidence and severity of peritonitis, and on surrogate parameters of biocompatibility and carbonyl stress).	2 months run in 10 months observation	No