Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ended
Participants planned
310
Countries
1
Sites
1
Patent ductus arteriosus (PDA)
The objective of this study is to evaluate the clinical impact, efficacy and safety of combination regime (Ibuprofen + IV Acetaminophen) for the first treatment course for PDA in ELGANs vs. Ibuprofen alone (current standard treatment). Primary objective: To reduce the incidence of bronchopulmonary dysplasia or death in…
Key facts
- Sponsor
- Royal College Of Surgeons In Ireland
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14]
- Trial duration
- 7 Aug 2024 → 6 Feb 2026
- Decision date (initial)
- 2023-07-28
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Mount Sinai Hospital
External identifiers
- EU CT number
- 2023-503209-13-00
- ClinicalTrials.gov
- NCT05340582
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Safety, Efficacy
The objective of this study is to evaluate the clinical impact, efficacy and safety of combination regime (Ibuprofen + IV Acetaminophen) for the first treatment course for PDA in ELGANs vs. Ibuprofen alone (current standard treatment).
Primary objective: To reduce the incidence of bronchopulmonary dysplasia or death in ELGANs receiving pharmacotherapy for PDA, by reducing treatment failure with the use of combination regime.
Secondary objectives 1
- Secondary objective: To examine the safety and impact of the combination regime on other neonatal morbidities.
Conditions and MedDRA coding
Patent ductus arteriosus (PDA)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | LLT | 10034129 | Patent ductus arteriosis | 10010331 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- 1. Preterm infants born <27+0 weeks gestational age admitted to one of four study NICUs: Mount Sinai Hospital, Sunnybrook Health Sciences Centre, McMaster Children’s Hospital, or the Rotunda Hospital
- 2. Permission given by the attending clinician to approach and then consent obtained from parents
- 3. Diagnosis of PDA ≥ 1.5 mm on echocardiography with unrestrictive predominantly left to right shunt
- 4. Designated to receive first treatment course with intravenous or enteral ibuprofen, as decided by the attending team.
Exclusion criteria 10
- 1. Chromosomal anomaly
- 2. Pre-treatment renal dysfunction defined as urine output < 1ml/kg/hour for the previous 24 hours or serum creatinine > 100 micromol/L
- 3. Pre-treatment hepatic dysfunction defined as serum aminotransferase (ALT) > 100 units/L94
- 4. Platelet count <50,000 per microliter and no plan to transfuse platelets
- 5. Permission denied by the attending clinician to approach parents
- 6. Parental consent not available
- 7. Previous exposure to PDA medical treatment with any drug (prophylactic indomethacin use for prevention of intraventricular hemorrhage will not be considered as PDA treatment).
- 8. Use of any other investigational medicinal product within previous 30 days
- 9. Any other medical condition/or treatment that contraindicates treatment with paracetamol or ibuprofen, such ashypersensitivity to paracetamol, propacetamol hydrochloride, or to any of the excipients listed in Section 6.1 of the SmPC for Paracetamol 10mg/ml solution for infusion
- 10. Cases of severe hepatocellular insufficiency.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Primary outcome: Composite of pre-discharge mortality or any grade BPD, defined as need for oxygen or positive pressure respiratory support at 36 weeks postmenstrual age.
Secondary endpoints 2
- i) PDA treatment success, defined as PDA closure or becoming insignificant [diameter <1.5 mm]. ii) Renal or hepatic dysfunction occurring within 7 days of treatment initiation, as defined under exclusion criteria. iii) Further exposure to PDA treatments (these will be as per units’ standard practice, not part of this study). iv) Procedure for PDA closure. v)Mortality
- vi) severity of BPD at 36 weeks postmenstrual age using Jensen’s criteria recently shown to be the definition which best predicted early childhood morbidities (grade 1, nasal cannula ≤2 L/min; grade 2, nasal cannula >2 L/min or noninvasive positive airway pressure; grade 3, invasive mechanical ventilation), vii) NEC ≥ stage 2A. viii) Duration (days) of invasive or non-invasive respiratory support. ix) Diuretic use during NICU stay. x) Exposure to postnatal steroids. xi) Sepsis during NICU stay
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
Paracetamol 10mg/ml solution for infusion
PRD607792 · Product
- Active substance
- Paracetamol
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 60 mg/kg milligram(s)/kilogram
- Max total dose
- 180 mg/kg milligram(s)/kilogram
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- N02BE01 — PARACETAMOL
- Marketing authorisation
- PA0736/035/001
- MA holder
- B.BRAUN MELSUNGEN AG
- MA country
- Ireland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Pedea 5 mg/ml solution for injection
PRD3705239 · Product
- Active substance
- Ibuprofen
- Substance synonyms
- (RS)-2-(4-isobutylphenyl)propionic acid, 2-(4-isobutylphenyl)propionic acid
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 20 mg/kg milligram(s)/kilogram
- Max total dose
- 40 mg/kg milligram(s)/kilogram
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- C01EB16 — -
- Marketing authorisation
- EU/1/04/284/001
- MA holder
- RECORDATI RARE DISEASES
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
Sodium Chloride 0.9% w/v Intravenous Infusion BP Solution for Infusion
PRD563915 · Product
- Active substance
- Sodium Chloride
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 0.9 % (W/V) percent weight/volume
- Max total dose
- 0.9 % (W/V) percent weight/volume
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- B05BB01 — ELECTROLYTES
- Marketing authorisation
- PA 0736/003/001
- MA holder
- B.BRAUN MELSUNGEN AG
- MA country
- Ireland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Royal College Of Surgeons In Ireland
- Sponsor organisation
- Royal College Of Surgeons In Ireland
- Address
- 123 Saint Stephen's Green
- City
- Dublin 2
- Postcode
- D02 YN77
- Country
- Ireland
Scientific contact point
- Organisation
- Royal College Of Surgeons In Ireland
- Contact name
- Mandy Jackson
Public contact point
- Organisation
- Royal College Of Surgeons In Ireland
- Contact name
- Mandy Jackson
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Ireland | Ended | 75 | 1 |
| Rest of world
Canada
|
— | 235 | — |
Investigational sites
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 |
|---|---|---|---|---|---|
| Ireland | 2024-05-08 | 2024-05-08 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Temporary halts 1 · Art. 38 CTR
Temporary halt TH-34456
- Halt date
- 2024-07-10
- Member states concerned
- Ireland
- Publication date
- 2024-07-11
- Reason
- Study management related
- Explanation
- GCP compliance issues, in particular relating to safety reporting (e.g. co-morbidities occurring long after treated condition has resolved and IMP has been discontinued).
- Follow-up measures
- Currently only one participant has been enrolled. The treated condition for this participant has resolved and the participant is no longer receiving IMP (since May). Participant is very unwell from conditions related to prematurity and unrelated to the trial or the IMP.
Plan is to review safety reporting with investigator team and to update the protocol to reduce need for reporting of co-morbidities occurring after treated condition has resolved and IMP has been discontinued. - Benefit-risk balance changed
- No
- Treatment stopped
- No
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 11 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | ACEDUCT Group Specific Appendix Ireland__V1 123Mar2023 | 1 |
| Protocol (for publication) | EU Study Protocol ACEDUCT_V3 18Jul2024_Clean | 3 |
| Protocol (for publication) | EU Study Protocol ACEDUCT_V4 15Apr25_Clean | 4 |
| Protocol (for publication) | Study Protocol ACEDUCT_v2_May12 2022 | 2 |
| Recruitment arrangements (for publication) | NREC-CT-Recruitement-and-informed-consent-procedureACEDUCT | 1 |
| Subject information and informed consent form (for publication) | ACEDUCT Maternal PIL ICF V2 point1 19Mar2025 Clean | 2.1 |
| Subject information and informed consent form (for publication) | ACEDUCT Parent Information Leaflet and consent form_V1 13Feb2023 | 1 |
| Subject information and informed consent form (for publication) | ACEDUCT Parent Information Leaflet and consent form_V2 point1 19Mar2025 Clean | 2.1 |
| Summary of Product Characteristics (SmPC) (for publication) | Paracetamol 10mg ml solution for infusion BBraun | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | pedea-epar-product-information_en | 1 |
| Synopsis of the protocol (for publication) | EU Study Protocol ACEDUCT_V3 16Sept2024_Clean | 3 |
Application history
5 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-04-05 | Ireland | Acceptable 2023-07-24
|
2023-07-28 |
| 2 | SUBSTANTIAL MODIFICATION | SM-3 | 2024-01-11 | Ireland | Acceptable 2024-03-27
|
2024-03-27 |
| 3 | SUBSTANTIAL MODIFICATION | SM-5 | 2024-07-22 | Ireland | Acceptable 2024-10-09
|
2024-10-09 |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-03-19 | Ireland | Acceptable 2024-10-09
|
2025-03-19 |
| 5 | SUBSTANTIAL MODIFICATION | SM-7 | 2025-05-26 | Ireland | Acceptable 2025-08-05
|
2025-09-02 |