Clinical Trials Register

Summary
EudraCT Number:	2020-002756-21
Sponsor's Protocol Code Number:	1663/2020
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-01-14
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

Austria - BASG

A.2

EudraCT number

2020-002756-21

A.3

Full title of the trial

Plasma Pharmacokinetics of Prophylactic Cefazolin Administered for Cardiac Surgery: Comparison of Cardiopulmonary Bypass Priming with Additive Human Albumin 20% vs.Pure Crystalloid Priming: A single center, prospective, randomized and controlled trial

Blutplasma Konzentrationen von prophylaktischem Antibiotikum (Cefazolin) während herzchirurgischen Eingriffen: Einfluss von Albumingabe im Vergleich zur Standard-Primingfüllung der Herz-Lungen-Maschine: Eine monozentrische, prospektive, randomisierte und kontrollierte Studie

A.3.1

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

Plasma pharmakocinetics of prophylactic Cefazolin administration for cardiac surgery: comparison of cardiopulmonary bypass priming with additive human Albumin 20% vs pure crystalloid priming

Plasma Pharmakokinetik von prophylaktisch verabreichtem Cefazolin während Herzchirurgie: Vergleich von Herz-Lungenmaschinen-Priming mit Zusatz von humanem Albumin 20% vs kristalloidem Priming

A.3.2

Name or abbreviated title of the trial where available

HLM_Albumin

A.4.1

Sponsor's protocol code number

1663/2020

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	Department of Cardiothoracic Anesthesia and Intensive Care Medicine, Medical University of Vienna
B.1.3.4	Country	Austria
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Cardiothoracic Anesth & Intensive Care Med, MUV
B.4.2	Country	Austria
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Cardiothoracic Anesth & Intensive Care Med, MUV
B.5.2	Functional name of contact point	Office
B.5.3	Address:
B.5.3.1	Street Address	Währinger Gürtel 18-20
B.5.3.2	Town/ city	Vienna
B.5.3.3	Post code	1090
B.5.3.4	Country	Austria
B.5.4	Telephone number	004301404004109
B.5.5	Fax number	004301404004110
B.5.6	E-mail	htg@meduniwien.ac.at

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	Human Albumin "CSL Behring" 20% Infusionslösung
D.2.1.1.2	Name of the Marketing Authorisation holder	CSL Behring GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Austria
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	Human Albumin “CSL Behring” 20% Infusionslösung
D.3.2	Product code	908884214165
D.3.4	Pharmaceutical form	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.3.8	INN - Proposed INN	human albumin
D.3.9.1	CAS number	9048-46-8
D.3.9.4	EV Substance Code	SUB20885
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	200
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	Yes
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	No

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

This is a pharmacokinetic trial for patients undergoing cardiac surgery. It will be investigated whether cardiopulmonary bypass priming substituted with human albumin 20% has an effect on the pharmacokinetics of prophylactic Cefazolin versus standard priming. The information retrieved by these investigations will help to optimize antiinfective treatment in patients undergoing cardiac surgery.

E.1.1.1

Medical condition in easily understood language

Investigation of the influence of albumin on the pharmacokinetics of prophylactic Cefazolin in patients undergoing cardiac surgery.

E.1.1.2

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Hypoalbuminemia is a common feature in patients undergoing cardiac surgery due to the initial volume load provided by the heart lung machine. The use of crystalloid priming was shown to be safe in coronary artery bypass grafting surgery in adults. However, there is some debate on the impact of low plasma colloid pressure, especially hypoalbuminemia and the changes in pharmacokinetics of plasma protein bound antibiotics. Hypoalbuminemia leads to an increased clearance and therefore a decreased AUC of the effective unbound form of plasma protein bound antibiotics. In this study, we want to investigate the pharmacokinetic effects of Cefazolin comparing patients with normal and patients with reduced albumin levels during cardiac surgery.

E.2.2

Secondary objectives of the trial

We further want to evaluate if the substitution of the cardiopulmonary bypass priming with albumin has an effect on ICU stay, hospital, stay, time to extubation and rate of postoperative infections.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Written informed consent
• Patients undergoing elective aortic valve repair
• Patients undergoing elective mitral valve repair
• Patients undergoing elective coronary artery bypass grafting
• Age: 18 – 85 years of age
• BMI: 20 -35 kg/m2
• No former allergic reaction to albumin
• No former allergic reaction to cefazolin
• Ejection fraction > 25%
• No former cardiac surgery
• Hemoglobin concentration > 11 mg/dL prior to surgery
• Serum creatinin < 2 mg/dL
• No significant hepatic disease (liver function tests < 3 X upper limit of normal)
• No history of coagulation disorders
• No signs of local or systemic infection
• No antibiotic therapy within the last 3 days

E.4

Principal exclusion criteria

• No informed consent
• Emergency cardiac surgery
• History of hypersensitivity to ß-lactam antibiotics
• History of allergic reaction to albumin
• Infection at site of surgery
• Systemic infection (endocarditis)
• Antimicrobial therapy within 3 days of surgery
• Former cardiac surgery
• Hemoglobin concentration < 11 mg/dL prior to surgery
• Congestive heart failure with ejection fraction < 25%
• Significant hepatic disease (liver function tests < 3 X upper limit of normal)
• Renal impairment with serum creatinine > 2 mg/L and/or GFR <60mL/min
• Body Mass Index (BMI) < 20 kg/m2 or BMI > 35 kg/m2
• Pregnancy or missing pregnancy test
• Perioperative need of Levosimendan (will lead to drop out)
• Aortic clamping time >240 minutes (will lead to drop out)
• Extra corporal circuit time >400 minutes (will lead to drop out)

E.5 End points

E.5.1

Primary end point(s)

Area under the concentration time curve (AUC)
Max.Concentration (Cmax)
Clearance (CL)

E.5.1.1

Timepoint(s) of evaluation of this end point

After administration of albumin (single dose) on the study day.

E.5.2

Secondary end point(s)

Volume distribution (Vd)
Total proteins
Albumin concnetration
ICU Stay
Hospital Stay
Time to extubation
Rate of postoperative infections

E.5.2.1

Timepoint(s) of evaluation of this end point

on study days, for the whole duration of the study including follow-up of adverse events if necessary.

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

E.6.4

Safety

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

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

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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

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

adverse events occur wich are so serious that the resulting resikbenefit ratio becomes unacceptable
the number of drop outs is so large that proper conclusion of the trial is no longer a realistic possibility
parallel trialsreveal unacceptable risk
results of interim analyses and the status of drug development change, such that the trial would no longer be necessary
attempted or proven fraud
slow recruitment
poor quality of data
non-compliance with protocol

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.1.2.1

Number of subjects for this age range:

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2021-01-14.

Yes

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

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Patients undergoing cardiac surgery mostly have mild to severe heart conditions

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)

None

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

2021-02-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-12-02

P. End of Trial
P.	End of Trial Status	Ongoing

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