Clinical Trials Register

Summary
EudraCT Number:	2008-004175-22
Sponsor's Protocol Code Number:	HC-G-H-0803
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-01-27
Trial results	View 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

2008-004175-22

A.3

Full title of the trial

PROSPECTIVE, CONTROLLED, DOUBLE-BLIND, RANDOMIZED MULTICENTRIC STUDY
ON THE EFFICACY AND SAFETY OF A TARGET CONTROLLED PLASMA VOLUME REPLACEMENT THERAPY WITH A HYPER-ONCOTIC BALANCED HES 130/0.42 SOLUTION VS AN ISO-ONCOTIC BALANCED HES 130/0.42 SOLUTION COMPARED TO A BALANCED ELECTROLYTE SOLUTION IN ELECTIVE SURGERY OF THE PANCREATIC HEAD

A.3.1

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

Comparison of the efficacy and safety of three different solutions for restoring blood volume after bleeding during surgery of pancreatic cancer.

A.3.2

Name or abbreviated title of the trial where available

HES 130/042 10% vs 6% PPPD

A.4.1

Sponsor's protocol code number

HC-G-H-0803

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	Medical Scientific Affairs
B.5.3	Address:
B.5.3.1	Street Address	Am Schwerzelshof
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	004905661712334
B.5.5	Fax number	004905661752334
B.5.6	E-mail	alex.castellarnau@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	Tetraspan 10%
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.3.1	Product name	HES 130/042
D.3.4	Pharmaceutical form	Solution 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.3.9.2	Current sponsor code	HES 130/042
D.3.9.3	Other descriptive name	Poly(O-2-hydroxyethyl)starch
D.3.10	Strength
D.3.10.1	Concentration unit	g/l gram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100.0
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	Sodium Chloride
D.3.10	Strength
D.3.10.1	Concentration unit	g/l gram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	6.25
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	Potassium Chloride
D.3.10	Strength
D.3.10.1	Concentration unit	g/l gram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.30
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	Calcium Chloride dihydrate
D.3.10	Strength
D.3.10.1	Concentration unit	g/l gram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.37
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	Magnesium Chloride hexahydrate
D.3.10	Strength
D.3.10.1	Concentration unit	g/l gram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.20
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	Sodium Azetate trihydrate
D.3.10	Strength
D.3.10.1	Concentration unit	g/l gram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3.27
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	Malic Acid
D.3.10	Strength
D.3.10.1	Concentration unit	g/l gram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.67
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	Colloidal infusion solution for plasma volume replacement.
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	Tetraspan 6%
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.3.1	Product name	HES 130/042
D.3.4	Pharmaceutical form	Solution 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.3.9.2	Current sponsor code	HES 130/042
D.3.9.3	Other descriptive name	Poly(O-2-hydroxyethyl)starch
D.3.10	Strength
D.3.10.1	Concentration unit	g/l gram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	60.0
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	Sodium Chloride
D.3.10	Strength
D.3.10.1	Concentration unit	g/l gram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	6.25
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	Potassium Chloride
D.3.10	Strength
D.3.10.1	Concentration unit	g/l gram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.30
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	Calcium Chloride dihydrate
D.3.10	Strength
D.3.10.1	Concentration unit	g/l gram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.37
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	Magnesium Chloride hexahydrate
D.3.10	Strength
D.3.10.1	Concentration unit	g/l gram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.20
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	Sodium Azetate trihydrate
D.3.10	Strength
D.3.10.1	Concentration unit	g/l gram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3.27
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	Malic Acid
D.3.10	Strength
D.3.10.1	Concentration unit	g/l gram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.67
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	Colloidal infusion solution for plasma volume replacement.
D.IMP: 3
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	Sterofundin ISO
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	Solution 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	Sodium Chloride
D.3.10	Strength
D.3.10.1	Concentration unit	g/l gram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	6.8
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	Potassium Chloride
D.3.10	Strength
D.3.10.1	Concentration unit	g/l gram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.30
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	Calcium Chloride dihydrate
D.3.10	Strength
D.3.10.1	Concentration unit	g/l gram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.37
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	Magnesium Chloride hexahydrate
D.3.10	Strength
D.3.10.1	Concentration unit	g/l gram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.20
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	Sodium Acetate trihydrate
D.3.10	Strength
D.3.10.1	Concentration unit	g/l gram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3.27
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	Malic Acid
D.3.10	Strength
D.3.10.1	Concentration unit	g/l gram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.67
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	Balanced solution for intravenous infusion.

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

Intraoperative plasma volume replacement requirement in elective surgery of the pancreatic head (pylorus preserving pancreatic-duodenectomy, PPPD)

E.1.1.1

Medical condition in easily understood language

Replacement of lost blood volume during surgery of pancreatic cancer.

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	LLT
E.1.2	Classification code	10059909
E.1.2	Term	Volume plasma
E.1.2	System Organ Class	10022891 - Investigations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

It is the primary aim of the planned study to investigate on the efficacy of target controlled fluid therapy with a hyper-oncotic compared to an iso-oncotic balanced HES 130/0.42 solution in adult patients undergoing elective pancreatic surgery.

E.2.2

Secondary objectives of the trial

Investigation of safety and secondary efficacy parameters of the balanced HES 130/0.42 solutions and of the balanced electrolyte solution.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Male or female patients older than18 years of age and less than 80 years of age. Women of child bearing potential must test negative on standard pregnancy test (urine).
- Patients scheduled to undergo elective surgery of the pancreatic head (e.g. PPPD)
- Patients who are willing to give of voluntary consent to participate in the study, following a full explanation of the nature and purpose of the study, by signing the informed consent form approved by the Institutional Ethics Committee (IEC) prior to all evaluations.

E.4

Principal exclusion criteria

- Patients of ASA-class > III
- Heart failure defined as NYHA class>2
- Aneurysm of the ascending and thoracic aorta
- Patients with Zenker’s diverticle
- Local oesophageal disease (oesophageal stricture, oesophageal varices, previous oesophageal surgery in past 6 months before study inclusion, pharyngeal pouch)
- Patients receiving haemodialysis
- Patients with known bleeding diatheses
- Any bleeding disorder known from patient’s history
- Patients with a haematocrit  25% despite pre-op transfusion
- Renal insufficiency (serum creatinine > 130 µmol/l or >1.5 mg/dl) or oliguria or anuria
- Impaired hepatic function defined as MELD > 10 or liver cirrhosis Child-Pugh B or C
- Additional contra-indications for either Tetraspan 6%, Tetraspan 10% and Sterofundin Iso
- Pregnancy or lactation period
- Simultaneous participation in another interventional clinical trial (AMG or MPG studies)
- Emergencies

E.5 End points

E.5.1

Primary end point(s)

A multiple primary endpoint is defined which is “the intra-operative amount (in mLs) of colloidal volume replacement therapy during target directed volume replacement therapy” as the first primary endpoint and “days until fully on oral (solid) diet” as the second primary endpoint (full on oral diet is defined by the absence of parenteral nutrition).

E.5.1.1

Timepoint(s) of evaluation of this end point

The study ends on postoperative Day 15 or discharge from hospital whatever occurs first.

E.5.2

Secondary end point(s)

Secondary objectives are the investigation of safety and efficacy parameters like blood coagulation, perioperative blood loss, anastomotic or bowel leakage, renal function, haemodynamics, postoperative inflammation, intraabdominal pressure, adverse events and amount of given blood products (RBC, FFP, PC). Furthermore, descriptive comparison of the hyper- and iso-oncotic volume replacement therapy with HES to volume replacement therapy with a crystalloid alone will be made.

E.5.2.1

Timepoint(s) of evaluation of this end point

The study ends on postoperative Day 15 or discharge from hospital whatever occurs first.

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

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

Information not present in EudraCT

E.7.1.2

Bioequivalence study

Information not present in EudraCT

E.7.1.3

Other

Information not present in EudraCT

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

Information not present in EudraCT

E.8.1.3

Single blind

Information not present in EudraCT

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

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

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in 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

last visit last patient

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

Information not present in EudraCT

F.1.1.2

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

Information not present in EudraCT

F.1.1.3

Newborns (0-27 days)

Information not present in EudraCT

F.1.1.4

Infants and toddlers (28 days-23 months)

Information not present in EudraCT

F.1.1.5

Children (2-11years)

Information not present in EudraCT

F.1.1.6

Adolescents (12-17 years)

Information not present in EudraCT

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

200

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

227

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)

Patients will follow normal treatment for that condition.

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

2009-03-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-07-11

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