Clinical Trials Register

Summary
EudraCT Number:	2016-001863-35
Sponsor's Protocol Code Number:	THAM
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2016-06-28
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

Austria - BASG

A.2

EudraCT number

2016-001863-35

A.3

Full title of the trial

Effects of Tromethamine on Cerebral Oxygenation and Metabolism in Patients Suffering Intractable Intracranial Hypertension – an exploratory study.

Der Effekt von Tromethamine auf die zerebrale Oxygenierung und Metabolismus in der Behandlung von kritisch erhöhtem Hirndruck – eine explorative Studie

A.3.1

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

Effects of Tromethamine on Brain Oxygenation and Metabolism in Patients Suffering Intractable Intracranial Hypertension – an exploratory study.

Der Effekt von Tromethamine auf die Oxygenierung des Gehirns und den Gehirnstoffwechsel in der Behandlung von kritisch erhöhtem Hirndruck – eine explorative Studie

A.3.2

Name or abbreviated title of the trial where available

Effect of Tromethamine on Cerebral Oxygenation

Der Effekt von Tromethamine auf die zerebrale Oxygenierung

A.4.1

Sponsor's protocol code number

THAM

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	Universitätsklinik für Klinische Pharmakologie, Medizinische Universität Wien
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	Medical University Vienna, Department of Clinical Pharmacology
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	Medical University Vienna, Department of Clinical Pharmacology
B.5.2	Functional name of contact point	Secretary
B.5.3	Address:
B.5.3.1	Street Address	Spitalgasse 23
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	004314040029810

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	Tris 36,34% Braun
D.2.1.1.2	Name of the Marketing Authorisation holder	B. Braun Melsungen Aktiengesellschaft
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	Tris 36,34% Braun
D.3.2	Product code	6723632.00.00
D.3.4	Pharmaceutical form	Concentrate for 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.3.8	INN - Proposed INN	TROMETAMOL
D.3.9.1	CAS number	77-86-1
D.3.9.4	EV Substance Code	SUB11336MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mmol/ml millimole(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3
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	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

Critically ill patients (SAH, ICB, AVM bleedings, malignant MCA infarcts) under sedation and mechanical ventilation in need of multimodality monitoring, including brain tissue oxygen monitoring and microdialysis. In this population, elevated intracranial pressure (ICP) remains a major complication. As salvage therapy of intractable intracranial hypertension Tromethamine is often administered in an off-label indication for lowering ICP.

E.1.1.1

Medical condition in easily understood language

Life-threatening intracranial hypertension in patients with severe neurological disease, e.g. intracranial bleeding

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

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

We propose to investigate effects of tromethamine on ICP and regional brain tissue oxygen tension (ptiO2) as measured by Neurovent PTO microprobes in critically ill patients under sedation and mechanical ventilation at a neurosurgical ICU suffering with acute intractable ICP elevation.

E.2.2

Secondary objectives of the trial

effects of tromethamine 10, 30 and 60 minutes after first bolus administration on:
intracranial pressure
mean arterial pressure
cerebral perfusion pressure
cerebral metabolism measured by cerebral microdialysis (glucose, lactate, pyruvate, glycerol, and glutamate)
TCD flow velocities
arterial blood gas values (pH, pCO2, pO2, bicarbonate, base excess)

dosage and frequency of tromethamine administration
concomitant medication for ICP control

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- age > 18 years
- patient is in need of multimodality monitoring, including ICP, regional brain tissue oxygen tension (ptiO2) measurement and microdialysis
- Clinical indication for THAM administration for treatment of intractable intracranial hypertension (ICP > 20mmHg)

E.4

Principal exclusion criteria

- Patient age < 18 years
- blood pH > 7,5
- no need of multimodality monitoring
- mannitol administration within the last 3 hours (half-life time of 100min)
- immediate need for concomitant administration of mannitol

E.5 End points

E.5.1

Primary end point(s)

ptiO2 10, 30 and 60 minutes after tromethamine administration

E.5.1.1

Timepoint(s) of evaluation of this end point

10, 30 and 60 minutes after tromethamine administration

E.5.2

Secondary end point(s)

intracranial pressure
mean arterial pressure
cerebral perfusion pressure
cerebral metabolism measured by cerebral microdialysis (glucose, lactate, pyruvate, glycerol, and glutamate)
TCD flow velocities
arterial blood gas values (pH, pCO2, pO2, bicarbonate, base excess)

E.5.2.1

Timepoint(s) of evaluation of this end point

10, 30 and 60 minutes after tromethamine administration

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

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

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

E.8.1.1

Randomised

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

Yes

E.8.1.7.1

Other trial design description

exploratory pharmacodynamic open label single arm study

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

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
The trial will be terminated prematurely in any of the following cases
for example:
• Slow recruitment
• Poor quality of data
• Status of drug development changes
• Attempted or proven fraud

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 2016-06-28.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

Yes

F.3.3.4

Nursing women

Yes

F.3.3.5

Emergency situation

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

In view of the life-threating nature of the underlying disease, patients under sedation and mechanical ventilation are per definition incapable of giving consent.

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)

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

2016-06-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-06-07

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2023-05-29

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