Infusion of Gelatine Solutions in Pediatric Patients Aged up to 12 Years
Conditions: Treatment of Hypovolemia and Shock
Sponsor: B. Braun Melsungen AG

 
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Study Plan 
 
 
 
of a Non-Interventional Observational Study 
 
 
 
 
Infusion of gelatine solutions in pediatric patients  
aged up to 12 years 
 
GPS - Gelatine in Pediatric PatientS 
 
 
Study ID No.: HC-O-H-1406 
 
NCT02495285 
 
Date: 13.03.2019 
 
 
Marketing Authorisation Holder: 
 
B. Braun Melsungen AG 
Germany 
 
 
Organized and Financed by: 
 
B. Braun Melsungen AG 
Division Hospital Care 
Carl-Braun-Str. 1 
34212 Melsungen 
Germany 
 

 
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STUDY OVERVIEW  
Title 
Infusion of gelatine solutions in pediatric patients aged up to 12 years 
Acronym: Gelatines in Pediatric patientS (GPS) 
Product under investigation 
Plasma volume replacement solutions containing gelatine  
(Gelaspan® 4% & Gelofusine® 4%) 
Study design 
Prospective, non-interventional, international, multicentric 
observational cohort study  
Number of sites, countries  
 10 European centers (e.g., Austria, France, Germany, Italy) 
Phase 
Post-authorization, non-interventional, clinical study voluntarily 
performed by Marketing Authorization Holder (MAH) 
Indication 
Treatment of hypovolemia and shock 
Primary objective and 
variable 
To gain additional information (dosing used during different surgeries) 
during routine clinical practice when used in pediatric population 
Secondary objectives and 
variables 
Further evaluation of safety and efficacy based on routinely measured 
clinical parameters: 
Safety: 
 
blood gas analysis (pH, HCO3-, pCO2, sO2, BE, Hb, Hct, lactate, 
Na+, K+, Ca2+, Cl-, glucose) 
 
serum prolin 
 
renal function (serum creatinine)  
 
(serious) adverse events / reactions including severity of an 
allergy and prick-test results in case of an 
anaphylactic/anaphylactoid reaction 
Efficacy: 
 
hemodynamic measures (heart rate, mean arterial pressure) 
Other: 
 
demographic data 
 
medical diagnosis leading to intervention 
 
concomitant disease  
 
pre-operative abnormalities  
 
indication for the administration of gelatine solution 
 
hemodynamics and hemodynamic monitoring 
 
concomitant infusions/medication (crystalloids, colloids, blood 
products, vasoactive drugs) 
 
surgery related data 
 
follow-up (post-operative bleeding complications and renal 
failure) 

final evaluation  
Patient population 
 
inclusion criteria 
 
 
 
age ≤ 12 years 
 
American Society of Anesthesiologists (ASA) risk score: ≤ III 

peri-operative infusion of gelatine solutions 

 
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 
exclusion criteria 
 
informed consent and/or data protection declaration signed by 
parents/legal guardians (according to local requirements)  
 
 
inclusion in another investigational study in the field of volume 
replacement which could interfere with the routine clinical 
practice regarding the administration of the gelatine solutions 
In addition contraindications as outlined in the valid local Summaries of 
Product Characteristics (SmPCs) have to be considered. 
Observational period per 
patient 
Observation period will start two hours prior first infusion of gelatine 
solutions and will end two hours after the last gelatine infusion 
stopped. A follow up will be furthermore recorded at discharge from 
the hospital or in-hospital 3 months after start of gelatine infusion, 
whatever occurs first. 
Study duration / milestones 
60 months after first patient in or termination after treatment of a 
maximum of 1500 patients, whatever occurs first. 
Interim analysis should be conducted after enrolment of at least 600 
patients. 
Sample size 
At least 1000 patients and in total a maximum of 1500 patients.  
 
 
 

 
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Statistical Analysis and Evaluation 
All data will be analyzed by means of tables, figures, listings and statistical tests if appropriate. 
The final programming will be performed after closure of the database by use of an appropriate 
statistical software package like SAS or SPSS.  
Deviations from the study plan will be assessed as plan violations if at least one of the inclusion 
or exclusion criteria is not fulfilled. All patients who received the product at least once will be 
included in the intention-to-treat analysis. All patients who received the product under 
investigation at least once without any plan violation will be included in the per protocol analysis.  
The patient data will be identified by the patient number assigned during data management, the 
study center, the treatment time and age of patient. 
 
The following statements are valid throughout the statistical analysis: 
Variables with metric or ordinal scale will be summarized with 
 
number of patients (N) 
 
minimum (Min) 
 
maximum (Max) 
 
median (ordinal variables) 
 
mean (metric variables) 
 
standard deviation (SD) 
 
(optional) frequency in the case of ordinal scale (n/%) 
 
(optional) upper and lower quartile (Q3 and Q1) 
 
95% confidence interval of the median/mean 
 
number of missing data (Nmiss) 
 
Categorical variables will be summarized with 
 
N 
 
frequency (n,%) 
 
Nmiss 
 
Missing data will be analyzed as such and will not be replaced by estimates. 
The following standard procedures for the comparison of subgroups (e.g. study center, country 
and age) are planned:  
 
Fisher’s exact test for binary data 
 
2 test for kx2 tables (k > 2) 
 
U test according to Wilcoxon-Mann-Whitney 
 
t-test for metric data 
 
ANOVA (analysis of variance) 
 
in case of small cell expectations occurring in the majority of the test situations data of 
ordinal scale will be analyzed by means of the U test instead of the 2 test. 
All statistical tests will be performed two-tailed with the pre-specified significance level of  = 5%.  
An interim analysis will be performed after treatment of at least 600 patients. 
The following tables inclusively descriptive statistics (see above) are planned: 
 
demographic data 
 
medical diagnosis leading to intervention 
 
concomitant disease(s) 
 
pre-operative abnormalities 
 
indication for and time of administration of gelatine solutions 
 
gelatine solution application  

 
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o dosage in relation to efficacy and safety during different kind of surgeries 
 
hemodynamic monitoring 
 
concomitant infusion/medication 
 
hemodynamic data  
 
blood gas analysis  
 
serum proline 
 
serum creatinine 
 
surgery related data 
 
AEs 
 
ARs 
 
SAEs / SARs 
 
follow-up at hospital discharge or in-hospital 3 months after first infusion of gelatine 
solutions, whatever occurs first 
 
personal review 
 
remarks and final conclusion 
 
Where appropriate corresponding figures (e.g. box-plot, bar-chart) will be presented.