Clinical Trials Register

Summary
EudraCT Number:	2018-001387-39
Sponsor's Protocol Code Number:	1.4
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:	2019-01-30
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

2018-001387-39

A.3

Full title of the trial

A prospective, randomized, controlled trial to assess the effect of long-term oxygen therapy on 6-minute walking distance, clinical parameters and hemodynamics in patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH)

Der Einfluss der langzeitigen Sauerstoff-Therapie auf den 6-Min-Gehtest, die hämodynamischen und klinischen Parametern bei Patienten mit pulmonal-arterieller Hypertonie (PAH) / chronisch-thromboembolischer pulmonaler Hypertonie (CTEPH)

A.3.1

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

The effect of oxygen therapy in patients with pulmonary Hypertension.

Effekt von Sauerstofftherapie bei Patienten mit Lungenhochdruck

A.3.2

Name or abbreviated title of the trial where available

SOPHA

A.4.1

Sponsor's protocol code number

1.4

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	Thoraxklinik-Heidelberg gGmbH
B.1.3.4	Country	Germany
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	VitalAire GmbH and OMT GmbH & Co. KG
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	Thoraxklinik Heidelberg gGmbH
B.5.2	Functional name of contact point	Centre for pulmonary hypertension
B.5.3	Address:
B.5.3.1	Street Address	Röntgenstr. 1
B.5.3.2	Town/ city	Heidelberg
B.5.3.3	Post code	69126
B.5.3.4	Country	Germany
B.5.4	Telephone number	+4962213968076
B.5.5	Fax number	+4962213961209
B.5.6	E-mail	PH-Studies.THOR@med.uni-heidelberg.de

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, liquid
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	Inhalation vapour, liquid
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.3.9.3	Other descriptive name	Sauerstoff
D.3.9.4	EV Substance Code	SUB14733MIG
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

pulmonary arterial hypertension (PAH) and chronic thromboembolic
pulmonary hypertension (CTEPH)

pulmonal-arterielle Hypertonie (PAH) chronisch-thromboembolische
pulmonale Hypertonie (CTEPH)

E.1.1.1

Medical condition in easily understood language

Patients with pulmonary Hypertension

Patienten mit Lungenhochdruck

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To determine the benefits for PH patients from a long-term oxygen therapy (LTOT) given continuously during ≥16h/day for 12 weeks, measured by improvement of exercise performance assessed by the 6 minute walking distance (6MWD)

E.2.2

Secondary objectives of the trial

1) To investigate effects of oxygen treatment on QoL, measured with SF-36 questionnaire 2) To determine the hemodynamic and functional responses during long term oxygen treatment by echocardiography and right heart catheterisation 3) To investigate the change of clinical parameters such as blood gas analysis, laboratory (NT-proBNP), WHO functional class (WHO-FC) 4) To assess time to worsening of oxygen saturation

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Patients in both groups (n = 40) with precapillary PH, WHO class I -IV (mPAP ≥ 25 mm Hg, pulmonary arterial occlusion pressure ≤15 mm Hg), who are stable on optimized pharmacological treatment for at least six weeks and who do not suffer from other cardio-pulmonary disease will be recruited if arterial or capillary O2 partial pressure is repeatedly (<60 mmHg; alternatively, 90% of O2 saturation) at rest and during physical activity hypoxemia still persist (O2 partial pressure <60 mmHg SpO2 90 % ). - men and women 18 years of age or older - patient is diagnosed with Pulmonary Arterial Hypertension (World Health Organization (WHO) Category Group 1-3 (by the WHO Clinical classification system)), including Idiopathic (IPAH), Heritable PAH (HPAH, Familial PAH), and CTEPH, with exceptions as noted in exclusion criteria - patient (or patient's legally authorized representative) is willing and able to provide written informed consent - patient is willing and able to comply with the protocol, including required follow-up visits - Patient experiences oxygen desaturations below 90% (or pO2 below 60 mmHg) at rest with oxygen desaturations below 90% (or pO2 below 60 mmHg) during physical activity - patient has a stable functional class of PAH with no changes of medication during the last six weeks before inclusion

E.4

Principal exclusion criteria

- Patient is a female who is pregnant, nursing, or of child bearing potential and is not on a reliable form of birth control - patient has already been treated with long-term oxygen therapy within the last 3 weeks. - patient with pulmonary venous hypertension - significant functional limitation in lung function tests (FEV1>60%,TLC <60%) and CT morphological signs of pulmonary disease - significant left heart disease, requires acute pharmacological or interventional treatment - unstable conditions requiring pharmacological or other treatment, intensive care or relevant severe concomitant disease - patient is enrolled, has participated within the last thirty days, or is planning to participate, in a concurrent drug and/or device study during the course of this clinical trial. Co-enrolment in concurrent trials is only allowed with documented pre-approval from the study manager that there is not a concern that co-enrolment could confound the results of this trial. - patient has been initiated on a new oral or parenteral PAH therapy in the last two months - patient has had a recent (within three months) or otherwise unresolved infection requiring antibiotic treatment - patient with a cardiac index (CI) <1.8L/min/m2 - patient is Functional Class IV (New York Heart Association (NYHA)) active smoking status - patient with severe resting desaturation (repeatedly SpO2 ≤85%) or severe exercise-induced desaturation (SpO2 <80% for ≥10 minutes)

E.5 End points

E.5.1

Primary end point(s)

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks after treatment start with or without oxygen

E.5.2

Secondary end point(s)

- To investigate effects of oxygen treatment on QoL, measured with SF-36 questionnaire - To determine the hemodynamic and functional responses during long term oxygen treatment by echocardiography and right heart catheterisation - To investigate the change of clinical parameters such as blood gas analysis, laboratory (NT-proBNP), WHO functional class (WHO-FC) - To assess time to worsening of oxygen saturation and time to clinical worsening

E.5.2.1

Timepoint(s) of evaluation of this end point

12 weeks after treatment start with or without oxygen

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

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

treatment without oxygen

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.1.2.1

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

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)

After the end of the study it is up to the judgment of the investigator to prescribe oxygen to all patients who might benefit from the treatment.
This decision will be based on the physician's and the patient's
estimation taking into account the observed individual treatment
effect, progression of disease, patient view and any comments from the Ethics Committee, if applicable. Patient care and monitoring will be performed in the patients' specialized Centers.

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

2019-03-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-01-23

P. End of Trial
P.	End of Trial Status	Completed

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