Randomised Placebo-Controlled Trial of Early Targeted Treatment of Patent Ductus Arteriosus with Paracetamol in Extremely Low Birth Weight Infants (ETAPA)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University College Dublin

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16], Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

26 Sep 2021 → ongoing

Decision date (initial)

2024-09-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Health Research Board (Ireland)

External identifiers

EU CT number

2024-516846-20-00

EudraCT number

2020-004245-37

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

Our primary objective is to compare the efficacy of early targeted treatment of PDA, in ELBW infants, with intravenous Paracetamol administration compared to placebo, in reducing the combined outcomes of PIVH, NEC and death before discharge.

Secondary objectives 1

1. To investigate the efficacy of early targeted treatment of PDA, in ELBW infants, with intravenous Paracetamol infusion compared with placebo, in preventing or reducing further known complications associated with PDA, as well as recording a number of known variables relating to prematurity from enrolment in the trial until discharge home from the hospital.

Conditions and MedDRA coding

Patent Ductus Arteriosus

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Neonates with birth weight less than 1000g, inborn or transferred from other hospitals
2. Decision made by the treating team to provide intensive care
3. Large PDA, defined as PDA with diameter greater than 1.5mm with non-restrictive flow (defined as diastolic flow less than 50% of systolic flow), determined by targeted functional neonatal echocardiography (fnECHO) between 6 and 12 hours of age

Exclusion criteria 12

1. Infants with major congenital anomalies including neural tube defects, major structural cardiac anomalies (excluding PDA/ASD/PFO/muscular VSD <5mm), abdominal wall defects and congenital diaphragmatic hernia and major dysmorphic features with an abnormal karyotype e.g. T21, T13, T18.
2. *Applicable to Czech Republic sites only: Birth Weight <500g*
3. *Applicable to Czech Repblic sites only: Birth Gestational Age <23 weeks of gestation*
4. The treating clinician does not intend to offer the infant intensive care.
5. Bidirectional shunt of PDA on fnECHO (defined as shunt exceeding 30% of the right to left proportion of the shunting).
6. Grade II – IV IVH on point of care cranial ultrasound (CRUSS) on screening (between six to twelve hours of age).
7. Pulmonary haemorrhage (PH) prior to study commencement
8. Severe persistent pulmonary hypertension of the newborn (PPHN).
9. History or examination suggestive of liver failure prior to study commencement
10. Written informed consent has not been obtained before the infant is 12 hours of age, or subjects’ parent(s)/guardian(s) withdraws consent prior to commencement of trial assessments or processes.
11. *Applicable to Czech Republic sites only: Proven Rhesus incompatibility with isoimmunisation*
12. Participation in another interventional study involving intravenous IMP

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of PIVH ≥grade II, NEC ≥grade IIa (Bell's staging), and death will be assessed at discharge.

Secondary endpoints 1

1. The secondary endpoint of CLD will be assessed at 36 weeks CGA. All other secondary endpoints will be assessed at discharge home, apart from developmental outcome at 2 years of corrected gestational age which will be assessed by Bayley’s assessment as phase 3 of ETAPA trial (and is not part of this protocol)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University College Dublin

Sponsor organisation

University College Dublin

Address

Catherine Mcauley Centre, 21 Nelson Street, Phibsborough 21 Nelson Street Phibsborough

City

Dublin 7

Postcode

DUB LIN7

Country

Ireland

Scientific contact point

Organisation

University College Dublin

Contact name

Jan Miletin

Public contact point

Organisation

University College Dublin

Contact name

Jan Miletin

Locations

2 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications