Clinical trial NCT03282955
Conditions: Patients Requiring Home Parenteral Nutrition
Sponsor: B. Braun Melsungen AG
Start date: 2018-01-08; Completion date: 2022-07-19
Enrollment: 74 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The aim of the trial is to investigate safety and tolerability of an Omega-3-FA-enriched lipid emulsion in adult patients with chronic intestinal failure in need of long-term HPN. It is aimed to show non-inferiority of the lipid emulsion Lipidem (investigational test product) in comparison to the lipid emulsion Lipofundin MCT (investigational reference product) with regard to liver function.

Detailed description:

Arms: arm 1: i.v. lipid emulsion containing fractionated fish oil (n-3 fatty acid triglycerides) arm 2: i.v. lipid emulsion
Interventions: intervention 1: Lipidem intervention 2: Lipofundin MCT 20%
Intervention descriptions: intervention 1: Lipoplus i.v. lipid emulsion for parenteral nutrition intervention 2: Lipofundin MCT 20% i.v. lipid emulsion for parenteral nutrition

Protocol documents:
Prot_SAP_000.pdf: 
Page 1 of 11 
 
Study Plan of 
A RANDOMIZED, CONTROLLED, DOUBLE-BLIND, 
MULTICENTER CLINICAL TRIAL ON HOME PARENTERAL 
NUTRITION USING AN OMEGA-3 FATTY ACID ENRICHED 
MCT/LCT LIPID EMULSION 
 
The HOME Study 
(HPN WITH OMEGA-3) 
STUDY IDENTIFICATION NO.: HC-G-H-1403 
NCT03282955 
Date of final applicable study plan: 21.05.2021 
 
Marketing Authorization Holder: 
 
B. Braun Melsungen AG 
Germany 
 
 
Organized and Financed by: 
 
B. Braun Melsungen AG 
Division Hospital Care 
Carl-Braun-Str. 1 
34212 Melsungen 
Germany 
 


Page 2 of 11 
 
STUDY OVERVIEW 
Title of Study 
A randomized, controlled, double-blind, multicenter clinical trial on home 
parenteral nutrition using an Omega-3 fatty acid enriched MCT/LCT lipid 
emulsion – The HOME Study (HPN with OMEGA-3) 
Investigational Products 
Investigational test product: 
Lipidem® / Lipoplus® 200 mg/ml 
(in the following referred as Lipidem) 
Investigational reference product: 
Lipofundin® MCT/LCT / Medialipide® 20% 
(in the following referred as Lipofundin MCT) 
Phase 
IV 
Study Design 
Prospective, randomized, controlled, double-blind, multicenter clinical trial 
performed in two parallel groups 
Number of Sites & 
Countries 
Up to 15 sites, planned countries: Poland, Belgium, France, Italy, Netherlands, 
Spain and United Kingdom 
Sample Size 
160 patients in total (80 per group) 
Indication 
Supply of energy, including a readily utilizable lipid component (medium-chain 
triglycerides) and essential omega-6 fatty acids and omega-3 fatty acids, as part 
of parenteral nutrition when oral or enteral nutrition is impossible, insufficient or 
contraindicated. 
Primary Objective 
Proof of safety and tolerability of home parenteral nutrition (HPN) with an 
Omega-3 fatty acid enriched MCT/LCT lipid emulsion in adult patients with 
chronic intestinal failure (CIF) in need of long-term HPN 
Primary Variable 
The primary endpoint of the study is the change of liver function parameters 
defined as the sum of the N(0,1)-transformed differences in bilirubin, Alanine 
transaminase (ALT) and Aspartate transaminase (AST) from baseline to visit 2. 
Secondary Objectives 
Further safety and efficacy evaluation 
Secondary Variables 
Variables indicated with * are calculated values 
Safety 
 Hepatic function 
 
Bilirubin (total and conjugated) 
 
Alanine transaminase (ALT) 
 
Aspartate transaminase (AST) 
 
AST/ALT ratio* 
 
Alkaline phosphatase (ALP) 
 
Gamma-glutamyl transpeptidase (GGT) 
 
 Blood count and coagulation 
 
White blood cells (WBCs) 


Page 3 of 11 
 
 
Red blood cells (RBCs) 
 
Hemoglobin (Hb) 
 
Hematocrit (Hct) 
 
Platelets 
 
International normalized ratio (INR) (if not possible prothrombin 
time [PT = Quick-value] is accepted) 
 
Activated partial thromboplastin time (aPTT)  
 
 Other biochemical parameters 
 
Blood glucose 
 
Electrolytes (Na, Cl, K, Ca, Mg, P) 
 
Serum creatinine 
 
Triglycerides 
 
Cholesterol 
 
High-density lipoprotein (HDL) cholesterol 
 
Low-density lipoprotein (LDL) cholesterol 
 
C-reactive protein (CRP) 
 
α-Tocopherol/Vitamin E (facultative if routinely assessed) 
 
 
Triene:tetraene ratio* obtained from fatty acid pattern in plasma 
 
 Adverse events (AEs) 
 
Efficacy 
 Fatty acid pattern in plasma and RBCs 
 BMI* 
 
Other variables 
 Demographic data 
 
Age 
 
Gender 
 
Ethnic origin 
 
Body height 
 
Body weight 
 
 Anamnesis 
 
Medical history relevant with regard to HPN  
o Pathological classification of IF 


Page 4 of 11 
 
o Underlying disease 
 
Concomitant disease(s) 
 
Ongoing medications 
 
Lipid emulsion(s) during the last 6 months 
 
Anamnestic peculiarities 
 
 Physical examination 
 Vital signs 
 Body weight change* 
 Quality of life (EQ-5DTM) 
 Concomitant medication 
 Energy requirements 
 PN regimen prescription 
 Treatment compliance* 
 Intake of oily fish meals 
 Study termination 
Patient Inclusion / 
Exclusion Criteria 
Inclusion criteria 
1. 
Signed informed consent available 
2. 
Male or female patients ≥ 18 years of age 
3. 
Patients with chronic intestinal failure receiving HPN including 
lipids in whom the parenteral macronutrients have not been changed by 
more than 10% for at least 3 months 
4. 
Patients receiving ≥ 3.0 g lipids/kg body weight per week 
 
Exclusion criteria 
1. 
Persistent high total bilirubin values in medical history of last 6 
months (> 40µmol/l) 
2. 
Patients in whom PN was interrupted for longer than 4 
continuous weeks in the preceding 6 months 
3. 
Patients with history of cancer and anti-cancer treatment within 
the last 2 years 
4. 
Hypersensitivity to egg, fish, peanut or soya-bean protein or to 
any of the active substances or excipients  
5. 
Patients treated in the past or currently with Teduglutide 
6. 
Contraindications to investigational products (if available from 
medical records) including: 
 Severe hyperlipidemia, including severe hypertriglyceridaemia (≥1000 
mg/dl or 11.4 mmol/l) 


Page 5 of 11 
 
 Severe coagulopathy 
 Intrahepatic cholestasis 
 Severe hepatic insufficiency 
 Severe renal insufficiency in absence of renal replacement therapy 
 Acute thromboembolic events 
 Fat embolism 
 Aggravating haemorrhagic diatheses 
 Metabolic acidosis 
7. 
General contraindications to parenteral nutrition (if available 
from medical records) including: 
 Unstable circulatory status with vital threat (states of collapse and shock) 
 Acute phase of cardiac infarction or stroke 
 Unstable metabolic conditions (e.g. decompensated diabetes mellitus, 
severe sepsis, coma of unknown origin) 
 Inadequate cellular oxygen supply 
 Disturbances of the electrolyte and fluid balance (e.g. hypokalaemia and 
hypotonic dehydration) 
 Acute pulmonary edema 
 Decompensated cardiac insufficiency 
8. Positive test for HIV, Hepatitis B or C (from medical history) 
9. Known or suspected drug or alcohol abuse  
10. Patients who are unwilling or mentally and/or physically unable to adhere 
to study procedures  
11. Participation in another interventional clinical trial in parallel or within 
three months prior to the start of this clinical trial 
12. Any medical condition that in the opinion of the investigator might put 
the subject at risk or interfere with patients participation 
For women with childbearing potential (i.e. females who are not chemically or 
surgically sterile or females who are not post-menopausal) 
13. Women of childbearing potential tested positive on standard pregnancy 
test (urine dipstick) 
14. Lactation 
15. Women of childbearing potential who do not agree to apply adequate 
contraception 
16. Persons of legal age who are the subject of a legal protection measure or 
who are unable to express their consent 
 
Investigational Test 
Product 
Lipidem 
 
1000 ml emulsion contain: 
 
Medium-chain triglycerides 
100.0 g 
Long-chain triglycerides (soybean oil) 
80.0 g 


Page 6 of 11 
 
Omega-3 fatty acid triglycerides 
20.0 g 
 
Essential fatty acids 
Linoleic acid (Omega-6) 
38.4 – 46.4 g 
Alpha-Linolenic acid (Omega-3) 
4.0 – 8.8 g 
Eicosapentanoic acid (EPA) and 
Docosahexanoic acid (DHA) 
8.6 – 17.2 g 
 
Additional excipients are: all-rac-α-Tocopherol, egg lecithin, 
glycerol, ascorbyl palmitate, water for injections 
 
Excipient(s) with known effect 
Sodium (as sodium hydroxide and sodium oleate) 
2.6 mmol/l 
 
Energy content 
7990 kJ ≈ 1910 kcal 
Theoretical osmolality 
approx. 410 mOsm/kg 
NaOH or HCl for titration to pH 7.4 
< 0,5 mmol/l 
pH 
6.5 – 8.5 
Investigational Reference 
Product 
 
 
 
Lipofundin MCT 
 
1000 ml emulsion contain: 
 
Medium-chain triglycerides 
100 g 
Long-chain triglycerides (soybean oil) 
100 g 
 
Essential fatty acids 
Linoleic acid (Omega-6) 
48.0 – 58.0 g 
Alpha-Linolenic acid (Omega-3) 
5.0 – 11.0 g 
 
Additional excipients are: all-rac-α-Tocopherol, egg lecithin, 
glycerol, sodium oleat, water for injections 
 
Energy content 
8095 kJ ≈ 1935 kcal  
Theoretical osmolarity 
approx. 380 mOsm/l 
NaOH or HCl for titration to pH 7.4 
< 0,5 mmol/l 
pH 
6.5 – 8.5 
Investigational Products 
Administration 
Method of Administration 
The administration of the investigational products (IPs) is performed 
intravenously. 
Dosage  
IP will be delivered as the lipid part of the parenteral nutrition (PN). 
Besides the lipid PN contains glucose, amino acids, electrolytes, trace 


Page 7 of 11 
 
elements and vitamins and will be administered according to the individual 
patient’s normal prescription. The weekly dose of IP will be at least 3.0 g 
lipid per kg body weight (BW) (corresponding 15 ml emulsion per kg BW 
and week). 
Treatment Duration 
Treatment with IP is projected for a period of 8 weeks on average and will 
not end before Visit 2. 
 
Visit Schedule 
Screening 
 Preferably during a regular patient monitoring visit 
 Patient information and signature of informed consent form (patient 
information sheet might be provided to the patient prior the visit) 
 Verification of inclusion and exclusion criteria 
 Pregnancy test (urine dipstick), if applicable 
 
Randomization 
 After check of all inclusion and exclusion criteria the patient will be 
randomized. 
 
Baseline 
The baseline assessment is performed after randomization on the day of 
screening. 
Documentation of: 
 Demographic data 
 Anamnesis 
 Physical examination 
Assessment of safety, efficacy and other variables (blood samples will be taken 
the earliest 3 hours after the last PN infusion): 
 Vital signs 
 Laboratory values from routine blood samples 
 Hepatic function (incl. blood samples for central laboratory analyses 
of primary variable) 
 Blood count and coagulation 
 Other biochemical parameters 
 Blood samples for central laboratory analyses of fatty acid pattern in 
RBCs and plasma  
 QoL 
 Concomitant medication 
 AEs continuously from start of study 
The patient will be provided with a patient diary for documentation of IP 


Page 8 of 11 
 
administration on a daily base. At baseline visit the patient diary will be handed 
out for the treatment period until visit 1.  
Prescription of PN including IP: 
 Treatment with IP will start within one week after baseline visit 
 If applicable, changes in prescription will be documented continuously 
throughout the course of the study 
 
Visit 1 = 4 weeks after start of IP infusion 
Study visit 1 should be preferably the same day of week and day time as the 
baseline visit. If this is not possible, it should be the same interval between PN 
infusion and visit day as it was for baseline (e.g. if baseline visit was after a day 
free of PN, visit 1 should be after a day free of PN as well). 
Assessments and procedures: 
 Pregnancy test (if applicable) 
Assessment of safety, efficacy and other variables (blood samples will be taken 
the earliest 3 hours after the last PN infusion): 
 Vital signs 
 Body weight 
 Laboratory results 
 Hepatic function (incl. blood samples for central laboratory analyses 
of primary variable) 
 Blood count and coagulation 
 Other blood biochemistry parameters 
 Treatment compliance will be documented in the electronic case report 
form (eCRF) on the basis of patient diary entries 
 Concomitant medication 
 AEs 
The investigator will collect the first part of the patient diary and check for 
accurateness and completeness. The data will be enter into the eCRF. 
A new patient diary will be handed out for the treatment period until visit 2. 
 
Visit 2 (final visit) = 4 weeks after visit 1 
Study visit 2 should be preferably the same day of week and day time as the 
baseline visit (and/or visit 1). If this is not possible, it should be the same 
interval between PN infusion and visit day as it was for baseline (e.g. if visit 1 
was after a day free of PN, visit 2 should be after a day free of PN as well). 
Assessment and procedures: 
 Pregnancy test (if applicable) 
Assessment of safety, efficacy and other variables (blood samples will be taken 
the earliest 3 hours after the last PN infusion): 
 Vital signs 


Page 9 of 11 
 
 Body weight 
 Laboratory results 
 Hepatic function (incl. blood samples for central laboratory analyses 
of primary variable) 
 Blood count and coagulation 
 Other blood biochemistry parameters 
 Blood samples for central laboratory analyses of fatty acid pattern in 
RBCs and plasma  
 QoL 
 Treatment compliance will be documented in the eCRF on the basis of 
patient diary entries 
 Concomitant medication 
 AEs 
Patient diary will be collected and data entered in the eCRF 
Visit 2 is the final study visit for the patient and study termination page of the 
eCRF will be completed. 
After this final visit no IP must be administered. The PN treatment will continue 
according to the decision of the physician with a regularly used lipid emulsion. 
Duration of Study per 
Patient 
Start of study: with randomization  
Treatment period (infusion of IP): 
 
Start of IP infusion within one week after randomization 
 
Treatment with IP is projected for a period of 8 weeks on average and 
will not end before visit 2 
End of study: Final visit (study visit 2) 
Study Schedule 
Planned start: Q1 / 2018 
Planned recruitment time: 5.5 years 
Planned last patient out: Q2 / 2023 
Statistical Methods 
Two sample t-test for mean difference assuming equal variances (testing non-
inferiority) 
Descriptive statistics including methods for the comparison of two groups (t-test, 
U test, χ2 test)
Randomization / Blinding  
Patients will be assigned at a 1:1 ratio to receive either Lipidem or Lipofundin 
MCT. The allocation to one of the two treatment groups will be performed by 
permuted block randomization with stratification for study site. 
The study is double-blind. 
Data and Safety 
Monitoring Board (DSMB) 
A DSMB will not be appointed. 
 
 
 
 


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Statistical Analysis and Evaluation 
Statistical methods 
All programming of tables, figures, listings and statistical analyses will be performed using SAS version 
9.4 (or higher). The planned statistics will be performed in accordance with the principles outlined by the 
guideline ICH E9.  
The primary endpoint of the study is the change of liver function parameters defined as the sum of the 
N(0,1)-transformed differences from baseline in ALT, AST, and bilirubin after 8 weeks of treatment. It is 
the aim to demonstrate non-inferiority of the primary endpoint with respect to 'deterioration in liver 
function' using the non-inferiority margin =1.151. This margin was derived as '/2' from a previous study 
on the use of lipid emulsions in HPN patients which provided a standard deviation of 2.3029 for the 
specified endpoint. The non-inferiority will be shown using the two-sample t-tests for mean differences 
assuming equal variances under the following conditions: 
 
distribution 
: 
normal 
 
method : 
 
exact 
 
number of sides : 
1 
 
alpha : 
 
0.025 
 
mean difference 
:1.151 (= non-inferiority margin ). 
 
The primary analysis will be performed for the Valid case set (FAS for sensitivity). No imputation will be 
performed.  
 
Thus, the t-test will compare the (one-sided) null hypothesis 
 
H0: 
T ≥ S +  
against the alternative hypothesis 
 
H1: 
T < S +  
on the level of 0.025, where T and S represent the increase of the primary endpoint upon T=test and 
S=standard. Non-inferiority (with non-inferiority margin =1.151) can be concluded, if the VCAS analysis 
yields an upper limit of the two-sided 95% confidence interval (or one-sided 97.5% confidence interval) for 
the treatment contrast of the primary endpoint lower than 1.151 and if this result is confirmed by the 
corresponding FAS analysis.  
Superiority of T vs S, i.e. H0: T ≥ S vs. H1: T < S, is demonstrated simultaneously, if the upper limit of 
the confidence interval is below zero for both the FAS analysis and and the VCAS analysis. 
 
Given the non-inferiority of T vs. S, the following procedure will be performed subsequently: 
 
breakdown of the multiple primary endpoint to its components ALT, AST, and bilirubin 
with unchanged level (Lehmacher et al., 1991). 
Further methods are descriptive statistics including standard procedures for the comparison of two groups 
(t-test, U test, 2 test). 
 


Page 11 of 11 
 
Interim Analysis 
No interim analyses are planned. 
 
Level of significance and power 
The primary endpoint will be tested one-sided with an significance level of =0.025. 
Tests of secondary variables will be carried out in the area of exploratory data analysis. Therefore, 
corresponding p-values are to be regarded as exploratory ones and no adjustments for multiple testing will 
be made. 
Sample size calculation is performed with a power of 80%. 
 
Statistical hypotheses 
The higher 'deterioration in liver function' is indicated by a higher sum of the N(0,1)-standardized changes 
from baseline to visit 2 in ALT, AST and bilirubin. Therefore, the hypotheses specified before will show – 
in case of significance – that the potential deterioration in liver function is not relevantly higher upon T than 
upon S. 
 
Data handling 
All data will be listed. Whenever applicable all tables, figures and listings will identify patients using the 
patient identification (ID) and time of evaluation. For data collected prior to randomization, patients will 
appear in the listings with the treatment to which they were subsequently allocated. 
The actual population presented in a table/figure/listing will be mentioned in the headings. 
Tables and listings will be produced in accordance with the principles outlined by the ICH E3 guideline. 
Handling missing data and outliers 
Every effort will be made to collect all data points in the study. The amount of missing data will be 
minimized by appropriate management of the randomized, prospective, trial, proper screening of subjects, 
and training of participating investigators and other authorized staff (e.g. nurses), monitors and study co-
coordinator. Since all patients who are randomized will be included in the primary analysis, in those 
instances where data are missing, missing values will not be imputed.  
 
Prior to database lock a blinded data review meeting will be held to identify remaining data issues, review 
listings/graphs specifically created for the data review meeting, to assess the impact of protocol violations 
on the interpretation of data and to trigger last database corrections or an SAP update as applicable. 
.