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

Sponsor

Heidelberg University (Other)

Overall Status

Completed

CT.gov ID

NCT01632046

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Renal Failure Peritoneal Membrane Disorder	Drug: lactate and bicarbonate buffered dialysis solutions	Phase 4

Detailed Description

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

Study Design

Study Type:

Interventional

Actual Enrollment :

42 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2004

Actual Primary Completion Date :

Mar 1, 2007

Actual Study Completion Date :

Mar 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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 %.	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. Other Names: BicaVera Balance
Active Comparator: 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 %.	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. Other Names: BicaVera Balance

Arm

Intervention/Treatment

Active Comparator: 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 %.

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.

Other Names:

BicaVera

Balance

Active Comparator: 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 %.

Drug: lactate and bicarbonate buffered dialysis solutions

Other Names:

BicaVera

Balance

Outcome Measures

Primary Outcome Measures

Evaluation of the effect of a lactate based and a bicarbonate based double-chambered, pH-neutral PD solution on peritoneal transport capacity in children. [2 months run in 10 months study period]
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.

Secondary Outcome Measures

Ultrafiltration [2 months run in 10 months observation]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Month to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	University Children's Hospital	Vienna	Austria	1090
2	University Children's Hospital	Helsinki	Finland	00029
3	University Children's Hospital	Strasbourg	France	67098
4	University Children's Hospital	Essen	Germany	45122
5	University Children´s Hospital	Hamburg	Germany	20246
6	University Children's Hospital	Jena	Germany	07740
7	University Children's Hospital	Milan	Italy	20122