Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ongoing, recruitment ended
Participants planned
560
Countries
1
Sites
10
Bronchiolitis
Primary objective: to investigate if an SpO2 threshold of 88% for children and adolescents admitted with respiratory distress results in a safe reduction of length of hospital stay, compared to an SpO2 threshold of 92%.
Key facts
- Sponsor
- Spaarne Gasthuis
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Respiratory Tract Diseases [C08]
- Trial duration
- 5 Sep 2023 → ongoing
- Decision date (initial)
- 2023-06-27
- Transition trial
- No
- Low-intervention
- Yes
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Amphia Hospital Science Fund · ZonMw · Spaarne Gasthuis Science Fund · Dutch Foundation for Asthma Prevention
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Therapy, Safety
Primary objective: to investigate if an SpO2 threshold of 88% for children and adolescents admitted with respiratory distress results in a safe reduction of length of hospital stay, compared to an SpO2 threshold of 92%.
Secondary objectives 1
- To investigate if an SpO2 threshold of 88% leads to differences in duration and severity of symptoms, readmissions, time to normal activity, patient and parent quality of life and cost-effectiveness compared to an SpO2 threshold of 92%.
Conditions and MedDRA coding
Bronchiolitis
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Children aged 6 weeks to 12 years
- Hospitalized with lower respiratory distress due to bronchiolitis, viral wheeze or lower respiratory tract infection
- Requiring supplemental oxygen (SpO2 <92% or otherwise indicated by the treating physician)
Exclusion criteria 6
- children with other pre-existing respiratory diseases, cardiovascular, neurological or hematological conditions
- children born <32 weeks gestational age
- previously included in the study
- considering questionnaires are only available in Dutch and English, children (of parents) with different languages will be excluded.
- children (of parents) without a stable internet connection needed for answering questionnaires
- children already included in other studies, which potentially interfere with this study
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- the time from admission to meeting all discharge criteria
Secondary endpoints 12
- Length of stay
- Number of PICU admissions
- Time spent on oxygen therapy
- Duration of symptoms
- Time from admission to return to normal health
- Time from admission to return to school/day care
- Unscheduled health care visits after discharge during follow-up
- Patient Quality of Life
- Parental anxiety
- Overall pediatric health
- Economic evaluation
- Reasons for starting oxygen therapy
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Conoxia Liquid, 100% v/v, medicinaal gas, vloeibaar gemaakt.
PRD1854589 · Product
- Active substance
- Oxygen
- Substance synonyms
- OXYGENIUM
- Pharmaceutical form
- MEDICINAL GAS, LIQUEFIED
- Route of administration
- RESPIRATORY USE
- Max daily dose
- 0 Other
- Max total dose
- 0 Other
- Max treatment duration
- 1 Week(s)
- Authorisation status
- Authorised
- ATC code
- V03AN01 — -
- Marketing authorisation
- RVG 112179
- MA holder
- LINDE GAS THERAPEUTICS BENELUX BV
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Spaarne Gasthuis
- Sponsor organisation
- Spaarne Gasthuis
- Address
- Spaarnepoort 1
- City
- Hoofddorp
- Postcode
- 2134 TM
- Country
- Netherlands
Scientific contact point
- Organisation
- Spaarne Gasthuis
- Contact name
- Annemie L. M. Boehmer
Public contact point
- Organisation
- Spaarne Gasthuis
- Contact name
- Annemie L. M. Boehmer
Locations
1 EU/EEA country · 10 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ongoing, recruitment ended | 560 | 10 |
| Rest of world | — | 0 | — |
Investigational sites
Medical Center Haaglanden
Pediatrics, Lijnbaan 32, 2512 VA, 's-Gravenhage
Stichting Rijnstate Ziekenhuis
Pediatrics, Wagnerlaan 55, 6815 AD, Arnhem
Martini Ziekenhuis / Centrum Bijzondere Tandheelkunde Martini Ziekenhuis
Pediatrics, Van Swietenplein 1, 9728 NT, Groningen
Amphia Hospital
Pediatrics, Molengracht 21, 4818 CK, Breda
Canisius Wilhelmina Hospital
Pediatrics, Weg Door Jonkerbos 100, 6532 SZ, Nijmegen
St Antonius Hospital
Pediatrics, Koekoekslaan 1, 3435 CM, Nieuwegein
Spaarne Gasthuis
Pediatrics, Boerhaavelaan 22, 2035 RC, Haarlem
Tergooiziekenhuizen
Pediatrics, Van Riebeeckweg 212, 1213 XZ, Hilversum
Stichting Isala Klinieken
Pediatrics, Dokter Van Heesweg 2, 8025 AB, Zwolle
Stichting Sint Franciscus Vlietland Groep
Pediatrics, Kleiweg 500, 3045 PM, 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 |
|---|---|---|---|---|---|
| Netherlands | 2023-09-05 | 2023-09-05 | 2024-12-04 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Serious breaches 1 · Art. 52 CTR
Serious breach SB-56471
- Sponsor became aware
- 2024-11-07
- Date of breach
- 2024-11-04
- Submission date
- 2024-11-08
- Member states concerned
- Netherlands
- Categories
- Protocol
- Areas impacted
- Subject safety
- Benefit-risk balance changed
- No
- Description
- The inclusion and randomisation of a patient that fulfilled an exclusion criterion. The randomized patient was a 15-month old, born prematurely at 26 weeks gestational age , while <32 is an exclusion criterion. The patient was already on supplemental oxygen (with local protocol saturation target) before randomisation. The patient was randomised to the 88% saturation target group. Supplemental oxygen without applying the new saturation target was continued due to increased work of breathing, according to the standard operation procedure of the study protocol. Further clinical deterioration later prompted the patient to be transferred to the Paediatric Intensive Care Unit. Only after this transfer did the local investigator become aware of the exclusion criterium and was the patient withdrawn from the study (study protocol dictates standard care always resumes after PICU transfer). Investigation has shown that the randomised oxygen saturation target of 88% has never been applied and therefore has not influenced the treatment of the patient at any time. The OxyKids trial was designed with a safety precaution: physicians can always commence or continue supplemental oxygen for clinical reasons other than oxygen saturation. We have seen in all cases so far that this safety precaution is applied in the correct way. The full report of this patient is attached as supporting information.
Wrongful inclusion and randomisation has previously occurred during the trial in 10 cases, out of 519 currently included. Due to the potential safety risk illustrated by the above case we felt it prudent to take further action, as well as submit this serious breach. Protocol violations of all previous 10 cases have been submitted to the sponsor. None of these patients were exposed to lower oxygen saturation or experienced adverse events. Again, this is in line with the study design where oxygen can be started for other reasons than oxygen saturation. - Sponsor actions
- Even though the risk of actual undertreatment of patients not suitable for trial participation is estimated to be negligible due to the study design, we have instructed all local investigators to remind, and where necessary retrain, their staff on the exclusion criteria. To incorporate these in the informed consent procedure and double check before enrolling a patient. This e-mail with instruction has been sent on the 8th of November.
| Organisation | City | Country | Type |
|---|---|---|---|
| Martini Ziekenhuis / Centrum Bijzondere Tandheelkunde Martini Ziekenhuis | Groningen | Netherlands | Other |
| Tergooiziekenhuizen | Hilversum | Netherlands | Other |
| Amphia Hospital | Breda | Netherlands | Other |
| Stichting Sint Franciscus Vlietland Groep | Rotterdam | Netherlands | Other |
| Spaarne Gasthuis | Hoofddorp | Netherlands | Sponsor (non commercial) |
Application history
5 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-04-18 | Netherlands | Acceptable with conditions 2023-06-27
|
2023-06-27 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2023-09-01 | Netherlands | Acceptable with conditions 2023-06-27
|
2023-09-01 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2023-09-19 | Netherlands | Acceptable with conditions 2023-06-27
|
2023-09-19 |
| 4 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-02-06 | Netherlands | Acceptable 2024-02-26
|
2024-02-26 |
| 5 | NON SUBSTANTIAL MODIFICATION | NSM-3 | 2024-05-28 | Netherlands | Acceptable 2024-02-26
|
2024-05-28 |