Clinical Trials Register

Summary
EudraCT Number:	2011-003397-82
Sponsor's Protocol Code Number:	HC-G-H-0813
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-07-23
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2011-003397-82

A.3

Full title of the trial

Prospective, randomized, controlled, double-blind, parallel-group, mono-centre, explorative Phase IV trial on the efficacy and safety of a fish oil containing lipid emulsion versus a standard soybean oil-based lipid emulsion in patients with Acute Lung Injury

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Trial with two lipid emulsions already approved for artificial nutrition to evaluate possible differences in the efficacy and safety of a fish oil containing lipid emulsion versus a standard soybean oil-based lipid emulsion in patients with Acute Lung Injury

Studie mit zwei bereits für die künstliche Ernährung zugelassenen Fettemulsionen zur Klärung von möglichen Unterschieden der Wirksamkeit und Sicherheit einer Fischöl-haltigen Fettemulsion im Vergleich zu einer rein Sojaöl-haltigen Fettemulsion bei Patienten mit akutem Lungenversagen

A.4.1

Sponsor's protocol code number

HC-G-H-0813

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	B. Braun Melsungen AG
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	B. Braun Melsungen AG
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	B. Braun Melsungen AG
B.5.2	Functional name of contact point	Clinical Development, Hospital Care
B.5.3	Address:
B.5.3.1	Street Address	Carl-Braun-Str. 1
B.5.3.2	Town/ city	Melsungen
B.5.3.3	Post code	34212
B.5.3.4	Country	Germany
B.5.4	Telephone number	+495661712384
B.5.5	Fax number	+495661752384
B.5.6	E-mail	irmgard.hoellwarth@bbraun.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Lipidem 20 % (Germany)
D.2.1.1.2	Name of the Marketing Authorisation holder	B. Braun Melsungen AG
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Emulsion for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	soy bean oil
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	8
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	medium chain triglycerides
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	omega 3 acid triglycerides
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	Emulsion for parenteral nutrition
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Lipofundin N 20 %
D.2.1.1.2	Name of the Marketing Authorisation holder	B. Braun Melsungen AG
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Emulsion for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	soy bean oil
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	Emulsion for parenteral nutrition

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Acute Lung Injury as a result of proven pneumonia (x-ray) or witnessed aspiration

E.1.1.1

Medical condition in easily understood language

Acute Lung Injury as a result of proven pneumonia (x-ray) or witnessed aspiration

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.1
E.1.2	Level	PT
E.1.2	Classification code	10069351
E.1.2	Term	Acute lung injury
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To investigate the impact of a parenteral nutrition regimen including a fish oil-enriched lipid emulsion on the pulmonary function in patients with Acute Lung Injury

E.2.2

Secondary objectives of the trial

To investigate safety and further efficacy variables of a fish oil-containing i.v. lipid emulsion as part of intensive care treatment

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Acute Lung Injury (ALI) as a result of proven pneumonia (x-ray) or wittnessed aspiration,
PaO2/FiO2 = 300 or less,
less than 72 hours since intubation or non-invasive ventilatory support by mask at screening,
expected need for parenteral nutrition for at least 5 days
full care on ICU,
male or female,
18 years of age or older

E.4

Principal exclusion criteria

Cardiogenic pulmonary oedema,
Previous or ongoing need for corticosteroid therapy with more than 0.1mg/kg /day prednisolon-equivalent or other immune-suppressive treatment,
Previous (< 1 year) or active treatment for solid or haematologic malignancy,
Serum Triglycerides > 300 mg/dl at screening,
Alterations of coagulation (thrombocytes < 100 Giga/l), aPTT > 60 sec, INR equal or > than 2.5 without therapeutic intevention,
Parenteral nutrition with SMOF or Omegaven,
Enteral nutrition with Pulmocare, Oxepa or Impact (any variety),
Autoimmune disease or HIV,
Known or suspected drug abuse,
Hypersensitivity to egg, fish, or soya-bean protein or to any of the active substances or excipients,
Severe renal failure without access to haemofiltration or dialysis,
Severe liver failure with bilirubin > 2.5 mg/dL,
Acute phase of myocardial infarction or stroke before timely scheduled interventional treatment and stabilization,
Acute thromboembolic disease until stabilization,
Lipid embolism

E.5 End points

E.5.1

Primary end point(s)

Change in blood oxigenation (PaO2/FiO2) from day 1 to day 6

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 1 before parenteral nutriton started and day 6 in the morning after 5
days (5 treatments) have been provided.

E.5.2

Secondary end point(s)

Safety variables:
GOT, GPT, GGT, AP, total & direct bilirubin, lipase, triglycerides,
cholesterol, blood glucose, sodium, potassium, calcium, phosphorus,
albumin, total protein, lactate, creatinine, urea, uric acid, CBC, INR,
aPTT, Hospital Anxiety and Depression Score (HADS), AE reporting
Efficacy variables:
length of ICU & hospital stay,
days free of (28 day timeframe): ICU care, ventilation, sedation,
catecholamine, renal replacement therapy,
rate of ICU complications, SOFA score, 28 & 90 day mortality,
Special variables: free fatty acid profile (AA, LA, ALA, DHA, EPA) and
total plasma fatty acids, apoptosis/proliferation markers of
lymphocytes, cytokine (TNF, IL-6, IL-8, IL-10), Th-17 cell, LTB4, LTB5,
resolvins (RvE1, NPDn)
Other variables:
weight, height, BMI, nutritional requirements & intake by parenteral and
enteral nutrition, concomittant therapy, Insulin, demographic data,
primary & secondary diagnosis, medical & medication history, vital
signs; first 24 hrs of ICU: APACHE II, GCS, SAPS II

E.5.2.1

Timepoint(s) of evaluation of this end point

Safety variables: daily, day 1 to day 16 (see above, except for HADS); AE documentation daily
Efficacy variables: daily, exept SOFA score until day 16 daily; mortality
day 28, day 90
For special variables: day 1, 4, 6, 16
Others: PN and EN intake daily

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

pilot , explorative trial

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

explorative

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.3

Elderly (>=65 years)

Yes

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Pts with ALI are usually intubated & sedated at the time of inclusion
Legally authorized persons for IC:
- competent court appoints representitive or
- patient named a representive.
Awoken pt will confirm or deny further participation (ICF)

Pt mit ALI sind idR intubiert und sediert
Rechtlich authorisierte Vertreter:
- Betreuer (Amtsgericht)
- Vorsorgebevollmächtigter
Erwachter Pt soll per ICF bestätigen oder ablehnen

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

If there is further need for parenteral or enteral nutrition, the patient will receive standard nutrition therapy (products) of the hospital

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-08-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-12-12

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2015-05-27

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