Clinical Trials Register

Summary
EudraCT Number:	2022-004166-37
Sponsor's Protocol Code Number:	100424
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:	2023-02-06
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

2022-004166-37

A.3

Full title of the trial

Hyperbaric oxygenation for patients with orthostatic dysregulation (postural orthostatic tachycardia) in Long- COVID. Prospectively randomized cross- over study.

Hyperbare Sauerstofftherapie bei Patienten mit orthostatischer Dysregulation im Rahmen von Long-Covid. Prospektive Cross-Over Studie.

A.3.1

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

Influence of 100% oxygen inhaled under hyperbaric conditions in patients
with cardiac symptoms after COVID-19 infection.

Hyperbare Sauerstofftherapie bei Patienten mit post-COVID-19
Symptomen.

A.4.1

Sponsor's protocol code number

100424

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	Division of Thoracic and Hyperbaric Surgery, Medical University Graz
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 of Graz
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 of Graz
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	Auenbruggerplatz 29
B.5.3.2	Town/ city	Graz
B.5.3.3	Post code	8036
B.5.3.4	Country	Austria
B.5.6	E-mail	freyja.smolle@medunigraz.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	Oxygen
D.2.1.1.2	Name of the Marketing Authorisation holder	Air-Liquide Austria 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	Sauerstoff medicAL
D.3.2	Product code	V03AN01
D.3.4	Pharmaceutical form	Inhalation vapour
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Oxygen
D.3.9.1	CAS number	7782-44-7
D.3.9.3	Other descriptive name	OXYGEN
D.3.9.4	EV Substance Code	SUB14733MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/V) percent weight/volume
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	99.5
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

Multiorgan symptoms after COVID-19 infection (Long COVID)

Multiorgan-Symptome nach COVID-19 Infektion (Long COVID)

E.1.1.1

Medical condition in easily understood language

Symptoms as breathing difficulties, fatigue, neuropathies and circulation problems in patients weeks to months after having contracted a COVID-19 infection.

Symptome wie Atembeschwerden, Mattigkeit, Neuropathien und Kreislaufprobleme bei Patienten Wochen bis Monate nach durchgemachter COVID-19 Infektion.

E.1.1.2

Therapeutic area

Body processes [G] - Biological Phenomena [G16]

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

The aim of the current study is to investigate the feasibility, safety and success of hyperbaric oxygen therapy in patients suffering from multiorgan symptoms considering orthostatic dysregulation (postural orthostatic tachycardia) after having contracted a COVID-19 infection (i.e."Long COVID").

Das Ziel dieser Studie ist es, die Machbarkeit, Sicherheit und Effektivität von hyperbarer Sauerstofftherapie bei Patienten mit Multiorgan- Symptomen unter spezieller Berücksichtigung der orthostatischen Dysregulation nach durchgemachter COVID-19 Infektion zu untersuchen (d.h. "Long COVID").

E.2.2

Secondary objectives of the trial

not applicable.

nicht zutreffend.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age 18 -90 years
2. Evident COVID-19 infection based on clinical diagnosis and at least one positive PCR test or Antibody test
3. Patients beyond 12 weeks after initial COVID-19 diagnosis, having failed to reassume their former life because of at least two lingering symptoms such as fatigue, dizziness, muscle weakness, insomnia, joint pain, myalgia, or headache lasting at least for 12 weeks (corresponding to grade 2- 4 of the current post-COVID-19 functional status scale)
4. Patients wit orthostatic dysregulation (postural orthostatic tachycardia) in Long- COVID
5. No active COVID-19 disease (as documented by negative PCR-test prior to enrolment).
6. Subject willing and able to read, understand and sign an informed consent and to do self-reporting according to questionnaire.

Alter: 18 - 90 Jahre
Evidente COVID-19 Infektion basierend auf klinischer Diagnose und einem positiven PCR-Test oder Antikörpernachweis
Patienten welche nach initialer COVID-19- Diagnose für die Dauer von mindestens 12 Wochen die entsprechende Long- COVID-Symptomatik von mind. zwei der folgenden Symptome aufweisen: Müdigkeit, Schwindel, Muskelschwäche, Schlaflosigkeit, Muskelschmerzen, Kopfschmerzen oder Gelenkschmerzen
Keine aktive COVID-19 Infektion (3 negative Tests im Abstand von 3 Tagen)
Fähigkeit zur Erteilung des Einverständnisses zur Teilnahme und zur Beantwortung des Fragebogens.

E.4

Principal exclusion criteria

1. Active malignancy
2. HBOT for any reason prior to study enrolment
3. Chest pathology incompatible with pressure changes (including untreated pneumothorax, bullous emphysema, moderate to severe asthma)
4. Ear or sinus pathology incompatible with pressure changes
5. Pregnancy or breast feeding
6. Patients unable to give informed consent

Aktuell bestehende, maligne Erkrankung
Anamnestisch durchgeführte HBO aus anderer Indikation
Thoraxpathologie, die keine Exposition in wechselnden Umgebungsdruck erlaubt (Bullöse Lungenveränderungen COPD III oder IV, Asthma, unbehandelter Pneumothorax)
Pathologie an Ohr oder Nebenhöhlen, die keinen Druckausgleich gestattet
Schwangere und Stillende
Nicht zurechnungsfähige oder nicht einwilligungsfähige Patienten

E.5 End points

E.5.1

Primary end point(s)

Hyperbaric oxygen treatment (HBO) leads to a significant improvement of the peak oxygen consumption of more than at least 15%, improvement of the blood gas values, the vital signs, the personal oxygen demand, the personal well being and the orthostatic dysregulation in patients with Long-COVID symptoms.

Die HBO-Therapie führt zu einer messbaren und statistisch signifikanten Verbesserung der maximalen Sauerstoffaufnahme (VO2 max) um mind. 15% Blutgaswerte, der Vitalparameter, des subjektiven Sauerstoffbedarfs und zu einer subjektiven Besserung der physischen Allgemeinsymptome insbesondere der orthostatischen Dysregulation bei Patienten mit Long COVID- Symptomatik.

E.5.1.1

Timepoint(s) of evaluation of this end point

1. At the start and after 4 weeks:
- Laboratory parameters (including Trop-T, D-Dimer, WBC, RBC, IL-6, CRP, Ferritin, CoV-19 antibodies)
- SF-36 questionnaire, Borg dyspnea score, fatigue assessment scale and Post-COVID-19 Functional Status scale (PCFS)
- Schellong test
- Bodyplethysmography
- Spiroergometry

2. During HBO (cross over time point)
- Laboratory parameters (including Trop-T, D-Dimer, WBC, RBC, IL-6, CRP, Ferritin, CoV-19 antibodies)
- SF-36 questionnaire, Borg dyspnea score, fatigue assessment scale and Post-COVID-19 Functional Status scale (PCFS)
- Schellong test
- Bodyplethysmography
- Spiroergometry

3. Regularly during HBO
- Blood pressure
- Heart rate
- Blood gases
- Need for oxygen-supplementation

4. 3 months
- Questionnaires mentioned above

1. Zu Beginn und nach 4 Wochen:
- Laborparameter (inkl. Trop-T, D-Dimer, Leukocyten, Blutbild, IL-6, CRP, Ferritin, CoV-19-Antikörper)
- Standardisierte Fragebögen: SF-36 questionnaire, Borg dyspnea score, fatigue assessment scale and Post-COVID-19 Functional Status scale (PCFS)
- Schellong Test
- Bodyplethysmographie
- Spiroergometrie

2. Während HBO (cross over):
- Laborparameter (inkl. Trop-T, D-Dimer, Leukocyten, Blutbild, IL-6, CRP, Ferritin, CoV-19-Antikörper)
- Standardisierte Fragebögen (s.o.)
- Schellong Test
- Bodyplethysmographie
- Spiroergometrie

3. Routinemäßig während HBO selbst:
- Blutdruck
- Puls
- Blutgase
- Sauerstoffbedarf

4. Nach 3 Monaten:
- Standardisierte Fragebögen (s.o.)

E.5.2

Secondary end point(s)

Effect of HBO treatment on laboratory parameters related to inflammation and epithelial damage, tissue oxygen levels, lung function parameters, Borg dyspnea score (46), fatigue assessment scale, post-COVID-19 functional status scale (PCFS) and parameters from the SF-36 questionnaire.

Effekt der HBO auf die laborchemischen Entzündungsparameter, Endothelschäden-assoziierte Blutparameter, Gewebssauerstoffspiegel, Lungenfunktion, subjektives Allgemeinbefinden, neurologische und cardio-vaskuläre Symptomatik.

E.5.2.1

Timepoint(s) of evaluation of this end point

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

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

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

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

Yes

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Pilotstudie

Pilot 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

Yes

E.8.2.3.1

Comparator description

Cross over -Design: beide Gruppen erhalten die HBO-Therapie, aber hintereinander bzw. abwechselnd

Cross over design: both groups receive HBO treatment alternately (2 weeks HBO and 2 weeks waiting)

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

Letzte Studienvisite des letzten Patienten

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 2023-02-06.

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

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)

Treatment and care after participants have ended participation in the trial is not different from usual treatment of Long COVID patients.

Die Behandlung und Betreuung von TeilnehmerInnen nach Ende der Teilnahme an der Studie unterscheidet sich nicht von der üblichen Behandlung von Patienten mit Long COVID.

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

2023-03-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-05-02

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

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