Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
64
Countries
1
Sites
7
unborn baby with developmental disorder of the left side of the heart
Evidence of efficacy of materno-fetal hyperoxygenation (MFHO) during the third trimester of pregnancy on growth of underdeveloped fetal left ventricular structures
Key facts
- Sponsor
- Universitaetsklinikum Erlangen AöR
- Participant type
- Pediatric, Patients
- Age range
- In Utero, 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Trial duration
- 25 Apr 2025 → ongoing
- Decision date (initial)
- 2024-03-25
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
External identifiers
- EU CT number
- 2024-512679-11-00
- EudraCT number
- 2022-000608-36
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Therapy, Safety
Evidence of efficacy of materno-fetal hyperoxygenation (MFHO) during the third trimester of pregnancy on growth of underdeveloped fetal left ventricular structures
Conditions and MedDRA coding
unborn baby with developmental disorder of the left side of the heart
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10021076 | Hypoplastic left heart syndrome | 100000004850 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- >= 18 years of age (mother)
- third trimester of pregnancy (mother)
- non-smoker (mother)
- A. uterina doppler ultrasound at least one-sided without pathological findings (mother)
- cardiac disorder with at least one underdeveloped left ventricular structure detected by echocardiography (fetus)
- sufficient fetal cardiac function (fetus)
Exclusion criteria 17
- alcohol or drug abuse (mother)
- multiple pregnancy (mother)
- adipositas permagna (BMI>40) (mother)
- diabetes melllitus, insulin-dependent (mother)
- obstetrical issues (e.g. Cervix uteri <25mm, premature contractions, preeclampsia, eclampsia, HELLP Syndrome, …) (mother)
- fetus impossible to evaluate by echocardiography (mother)
- patholog. utero-placental resistance (mother)
- cardiac failure (NYHA III/IV or decompensated) (mother)
- severe COPD, hypercapnia (mother)
- underlying disease or chromosomal abnormality which might influence the effect of MFHO (fetus)
- hemodynamic factors with influence on filling/emptying of the left heart which might affect MFHO efficacy (fetus)
- fetal cardiac failure (fetus)
- Hydrops fetalis (fetus)
- severe growth retardation (fetus)
- no flow in A. umbilicalis (fetus)
- severe extracardiac malformations (fetus)
- visit 2: inadequate response to O2 provocation during echocardiography (fetus)
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- median change of the sum of the Z-scores of the initially chosen echocardiographic fetal heart structures under O2 provocation at the time point PW35d0 (+/- 2 days) compared to the initial values on PW32d0 (+/- 2 days) under O2 provocation
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
LOX medicAL 100% (V/V) Gas zur medizinischen Anwendung, kälteverflüssigt
PRD334261 · Product
- Active substance
- Oxygen
- Pharmaceutical form
- MEDICINAL GAS, CRYOGENIC
- Route of administration
- INHALATION USE
- Max daily dose
- 4320 l litre(s)
- Max total dose
- 241920 l litre(s)
- Max treatment duration
- 8 Week(s)
- Authorisation status
- Authorised
- ATC code
- V03AN01 — -
- Marketing authorisation
- 6283297.00.00
- MA holder
- AIR LIQUIDE MEDICAL GMBH
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Universitaetsklinikum Erlangen AöR
- Sponsor organisation
- Universitaetsklinikum Erlangen AöR
- Address
- Maximiliansplatz 2, Innenstadt Innenstadt
- City
- Erlangen
- Postcode
- 91054
- Country
- Germany
Scientific contact point
- Organisation
- Universitaetsklinikum Erlangen AöR
- Contact name
- Prof. Dr. Holm Schneider
Public contact point
- Organisation
- Universitaetsklinikum Erlangen AöR
- Contact name
- Prof. Dr. Holm Schneider
Locations
1 EU/EEA country · 7 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Germany | Ongoing, recruiting | 64 | 7 |
| Rest of world | — | 0 | — |
Investigational sites
Universitaet Leipzig
Abteilung für Geburtsmedizin, Liebigstrasse 20a, Zentrum-Suedost, Leipzig
Barmherzige Brueder gemeinnuetzige Krankenhaus GmbH
Klinik St. Hedwig - Klinik für Frauenheilkunde und Geburtshilfe, Pruefeninger Strasse 86, Westenviertel, Regensburg
Herz Und Diabeteszentrum NRW Bad Oeynhausen Universitaetsklinik Der Ruhr-Universitaet Bochum
Klinik für Kinderkardiologie und angeborene Herzfehler, Georgstrasse 11, Innenstadt, Bad Oeynhausen
Universitaetsklinikum Mannheim GmbH
Deutsches Zentrum für Fetalchirurgie und minimal invasive Therapie (DZFT), Theodor-Kutzer-Ufer 1-3, Wohlgelegen, Mannheim
Klinikum Der Landeshauptstadt Stuttgart gKAöR
Olgasptial / Frauenklinik, Kriegsbergstrasse 62, Mitte, Stuttgart
Universitaetsklinikum Erlangen AöR
Kinder- und Jugendklinik, Loschgestrasse 15, Innenstadt, Erlangen
Universitaetsklinikum Essen AöR
Klinik für Frauenheilkunde und Geburtshilfe, Hufelandstrasse 55, Holsterhausen, Essen
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Germany | 2023-05-10 | 2023-08-18 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Temporary halts 1 · Art. 38 CTR
Temporary halt TH-70325
- Halt date
- 2025-02-11
- Member states concerned
- Germany
- Publication date
- 2025-02-11
- Reason
- Safety related (clinical or pre-clinical results)
- Explanation
- Für die klinische Prüfung HYPEROX wurde ein schwerwiegendes unerwünschtes Ereignis, für welches ein kausaler Zusammenhang mit der Prüfmedikation nicht ausgeschlossen werden kann (SAR), gemeldet. Im Studienprotokoll (Version 1.4 vom 10. Juli 2024) ist festgelegt, dass ein solches Ereignis eine Unterbrechung der klinischen Prüfung zur Folge haben soll.
- Follow-up measures
- Alle Rekrutierungsmaßnahmen wurden eingestellt, die Aufnahme weiterer Studienteilnehmer in die klinische Prüfung ist vorerst nicht möglich. Auf Grundlage der DSMB-Empfehlung wird entscheiden, ob und wann die klinische Prüfung fortgesetzt werden kann.
- Benefit-risk balance changed
- No
- Treatment stopped
- Yes
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 8 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_HYPEROX_Protocol_redacted | 1.5 |
| Protocol (for publication) | D4_HYPEROX_Subject_Card | 1.1 |
| Recruitment arrangements (for publication) | K1_Recruitment_IC_procedure_HYPEROX | 1.0 |
| Recruitment arrangements (for publication) | K2_Recruitment_material_HYPEROX | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS_ICF_HYPEROX_redacted | 1.5 |
| Subject information and informed consent form (for publication) | L2_Diary_HYPEROX | 1.2 |
| Subject information and informed consent form (for publication) | L2_Information_IMP_HYPEROX_redacted | 1.1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_LOX_medicAL | NA |
Application history
5 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-03-12 | Germany | Acceptable 2024-03-20
|
2024-03-25 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-07-19 | Germany | Acceptable 2024-08-22
|
2024-08-26 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-04-03 | Germany | Acceptable 2025-04-25
|
2025-04-28 |
| 4 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-10-10 | Germany | Acceptable | 2025-11-07 |
| 5 | SUBSTANTIAL MODIFICATION | SM-4 | 2026-02-10 | Germany | Acceptable | 2026-03-31 |