Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
396
Countries
2
Sites
19
Apnea of prematurity
The main objective of our trial is to investigate if doxapram is safe and effective in reducing the composite outcome of death and neurodevelopmental impairment/severe disability at 18 to 24 months corrected age as compared to placebo
Key facts
- Sponsor
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years
- Gender
- Male and Female
- Therapeutic area
- Not possible to specify
- Trial duration
- 16 Jun 2020 → ongoing
- Decision date (initial)
- 2024-11-13
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
External identifiers
- EU CT number
- 2024-515625-29-00
- EudraCT number
- 2019-003666-41
- ClinicalTrials.gov
- NCT04430790
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Safety, Therapy
The main objective of our trial is to investigate if doxapram is safe and effective in reducing the composite outcome of death and neurodevelopmental impairment/severe disability at 18 to 24 months corrected age as compared to placebo
Conditions and MedDRA coding
Apnea of prematurity
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 7
- Admitted to the NICU of one of the participating centres
- Written informed consent according to the national guidelines of both (the Netherlands) or at least one (Belgium and Canada) parent(s) or legal representatives
- Gestational age at birth < 29 weeks
- Postnatal age of at least 120 hours
- Caffeine therapy, adequately dosed
- Optimal non-invasively respiratory support according to the local treatment policy (with nasal CPAP or ventilation ((S)NIPPV, BIPAP/Duopap, nasal HFO)
- Frequent and/or severe apneas that require a medical intervention as judged by the attending physician
Exclusion criteria 5
- Previous use of open label doxapram
- Use of theophylline (to replace doxapram)
- Chromosomal defects (e.g. trisomy 13, 18, or 21)
- Major congenital malformations that: 1) Compromise lung function (e.g. surfactant protein deficiencies, congenital diaphragmatic hernia); 2) Result in chronic ventilation (e.g. Pierre Robin sequence), or 3) Increase the risk of death or adverse neurodevelopmental outcome (congenital cerebral malformations, chromosomal abnormalities)
- Palliative care or treatment limitations because of high risk of impaired outcome
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Primary outcome will be the composite outcome of death or severe disability at the age of 18-24 months corrected age. Both outcomes will also be analyzed seperately.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Doxapram Hydrochloride Monohydrate
PRD11644154 · Product
- Active substance
- Doxapram Hydrochloride Monohydrate
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 48 mg/kg milligram(s)/kilogram
- Max total dose
- 2 mg/kg/h milligram(s)/kilogram/hour
- Max treatment duration
- 10 Week(s)
- Authorisation status
- Not Authorised
- ATC code
- R07AB01 — DOXAPRAM
- MA holder
- ERASMUS MC
- Paediatric formulation
- No
- Orphan designation
- No
Placebo 1
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Sponsor organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Address
- Dr. Molewaterplein 40
- City
- Rotterdam
- Postcode
- 3015 GD
- Country
- Netherlands
Scientific contact point
- Organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Contact name
- S.H.P. Simons
Public contact point
- Organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Contact name
- S.H.P. Simons
Locations
2 EU/EEA countries · 19 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Belgium | Ongoing, recruiting | 100 | 10 |
| Netherlands | Ongoing, recruiting | 200 | 9 |
| Rest of world
Canada
|
— | 96 | — |
Investigational sites
Hopital Erasme
Neonatology, Lennikse Baan 808, 1070, Anderlecht
Cliniques Universitaires Saint-Luc
Neonatology, Hippokrateslaan 10, Batiment 54, Sint-Lambrechts-Woluwe
Ziekenhuis Aan De Stroom
Neonatology, Oosterveldlaan 24, 2610, Antwerp
Grand Hopital De Charleroi
Neonatology, Grand'rue 3, 6000, Charleroi
UZ Brussel
Neonatology, Laarbeeklaan 101, 1090, Jette
Antwerp University Hospital
Neonatology, Drie Eikenstraat 655, 2650, Edegem
Chirec
Neonatology, Boulevard Du Triomphe 201, 1160, Brussels
Ziekenhuis Oost Limburg
Neonatology, Synaps Park 1, 3600, Genk
UZ Leuven
Neonatology, Herestraat 49, 3000, Leuven
Az St-Jan Brugge-Oostende A.V.
Neonatology, Ruddershove 10, 8000, Brugge
Universitair Medisch Centrum Groningen
IC Neonatology, Hanzeplein 1, 9713 GZ, Groningen
Isala Klinieken Stichting
IC Neonatology, Dokter Van Heesweg 2, 8025 AB, Zwolle
Leids Universitair Medisch Centrum (LUMC)
IC Neonatology, Albinusdreef 2, 2333 ZA, Leiden
Amsterdam UMC Stichting
IC Neonatology, Meibergdreef 9, 1105 AZ, Amsterdam
Radboud universitair medisch centrum Stichting
IC Neonatology, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen
Universitair Medisch Centrum Utrecht
IC Neonatology, Heidelberglaan 100, 3584 CX, Utrecht
Maxima Medisch Centrum
IC Neonatology, Ds Theodor Fliednerstraat 1, 5631 BM, Eindhoven
Academisch Ziekenhuis Maastricht
IC Neonatology, P Debyelaan 25, 6229 HX, Maastricht
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
IC Neonatology, Wytemaweg 80, 3015 CN, Rotterdam
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 |
|---|---|---|---|---|---|
| Belgium | 2021-07-20 | 2021-11-12 | |||
| Netherlands | 2020-06-16 | 2020-06-18 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 9 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_2024-515625-29-00 | 11 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangement | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangement | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF with neuromonitoring | 5 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF with neuromonitoring_redacted | 6 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_FR | 4 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_redacted | 6 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_with blood samples_redacted | 5 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_with neuromonitoring_FR | 5 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-10-10 | Netherlands | Acceptable 2024-11-11
|
2024-11-11 |