Pulmonary Hypertension in Extremely Preterm Infants

Pulmonary Hypertension Clinical Trial

— PiEP  

Official title:

Pulmonary Hypertension in Extremely Preterm Infants - A Prospective Cohort Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05136235
• Other study ID #: PiEP study
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 2022
• Est. completion date: December 2025

Study information

• Verified date: October 2021
• Source: Universitair Ziekenhuis Brussel
• Contact: Barbara De Bisschop, MD
• Phone: 0032 2 477 77 21
• Email: barbara.debisschop[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Extremely preterm infants are at risk for developing bronchopulmonary dysplasia (BPD) and associated chronic pulmonary hypertension (PH), a consequence of altered pulmonary vasculature. This condition occurs in about 25% of babies with BPD, and the association grows with increasing BPD severity. Other risk factors have been described as well. Morbidity and mortality associated with prematurity and/or BPD increase significantly in the presence of PH.

Thus, international guidelines encourage the use of standardized screening protocols for this condition. However, several questions regarding these recommendations are left unanswered, such as a clear definition for PH in this population.

The research aim is to prospectively evaluate prevalence, risk factors and clinical course of PH in these children. The investigators aim to identify at-risk infants early on and ultimately improve survival making use of an early targeted intervention.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 350
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 2 Weeks

Eligibility

Inclusion Criteria: Preterm infants with

• Gestational age <28 0/7 weeks

• Birth weight <1000 grams

Exclusion Criteria:

• Major congenital malformations

• Structural airway or lung disease

• Congenital heart disease

• Lack of parental consent

Related Conditions & MeSH terms

• Bronchopulmonary Dysplasia
• Hypertension
• Hypertension, Pulmonary
• Premature Birth
• Pulmonary Hypertension

Intervention

Diagnostic Test:
• Echocardiography
There will be screened for pulmonary hypertension by means of serial echocardiographies during the study period
• NT-proBNP
At 36 weeks postmenstrual age there will be screened for pulmonary hypertension by means of an NT-proBNP measurement in a blood sample

Locations

Country	Name	City	State
n/a

Sponsors (7)

Lead Sponsor	Collaborator
Universitair Ziekenhuis Brussel	AZ Sint-Jan AV, GZA Ziekenhuizen Campus Sint-Augustinus, Universitaire Ziekenhuizen Leuven, University Hospital, Ghent, Ziekenhuis Netwerk Antwerpen (ZNA), Ziekenhuis Oost-Limburg

References & Publications (5)

Abman SH, Hansmann G, Archer SL, Ivy DD, Adatia I, Chung WK, Hanna BD, Rosenzweig EB, Raj JU, Cornfield D, Stenmark KR, Steinhorn R, Thébaud B, Fineman JR, Kuehne T, Feinstein JA, Friedberg MK, Earing M, Barst RJ, Keller RL, Kinsella JP, Mullen M, Deterding R, Kulik T, Mallory G, Humpl T, Wessel DL; American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; Council on Clinical Cardiology; Council on Cardiovascular Disease in the Young; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Surgery and Anesthesia; and the American Thoracic Society. Pediatric Pulmonary Hypertension: Guidelines From the American Heart Association and American Thoracic Society. Circulation. 2015 Nov 24;132(21):2037-99. doi: 10.1161/CIR.0000000000000329. Epub 2015 Nov 3. Erratum in: Circulation. 2016 Jan 26;133(4):e368. — View Citation

Arjaans S, Zwart EAH, Ploegstra MJ, Bos AF, Kooi EMW, Hillege HL, Berger RMF. Identification of gaps in the current knowledge on pulmonary hypertension in extremely preterm infants: A systematic review and meta-analysis. Paediatr Perinat Epidemiol. 2018 May;32(3):258-267. doi: 10.1111/ppe.12444. Epub 2018 Jan 17. Review. — View Citation

Hilgendorff A, Apitz C, Bonnet D, Hansmann G. Pulmonary hypertension associated with acute or chronic lung diseases in the preterm and term neonate and infant. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK. Heart. 2016 May;102 Suppl 2:ii49-56. doi: 10.1136/heartjnl-2015-308591. — View Citation

Krishnan U, Feinstein JA, Adatia I, Austin ED, Mullen MP, Hopper RK, Hanna B, Romer L, Keller RL, Fineman J, Steinhorn R, Kinsella JP, Ivy DD, Rosenzweig EB, Raj U, Humpl T, Abman SH; Pediatric Pulmonary Hypertension Network (PPHNet). Evaluation and Management of Pulmonary Hypertension in Children with Bronchopulmonary Dysplasia. J Pediatr. 2017 Sep;188:24-34.e1. doi: 10.1016/j.jpeds.2017.05.029. Epub 2017 Jun 20. Review. — View Citation

Levy PT, Jain A, Nawaytou H, Teitel D, Keller R, Fineman J, Steinhorn R, Abman SH, McNamara PJ; Pediatric Pulmonary Hypertension Network (PPHNet). Risk Assessment and Monitoring of Chronic Pulmonary Hypertension in Premature Infants. J Pediatr. 2020 Feb;217:199-209.e4. doi: 10.1016/j.jpeds.2019.10.034. Epub 2019 Nov 14. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Presence of pulmonary hypertension	Pulmonary hypertension will be defined as one or more of the following echocardiographic findings: Presence of a cardiac shunt with bidirectional or right-to-left flow; Estimated right ventricular systolic pressure (RVSP) >40 mmHg; RVSP/systemic systolic blood pressure (SBP) ratio >0.5; Presence of ventricular septal wall flattening	3-10 days of life (time depending on the timing of the first echocardiography)
Primary	Presence of pulmonary hypertension	Pulmonary hypertension will be defined as one or more of the following echocardiographic findings: Presence of a cardiac shunt with bidirectional or right-to-left flow; Estimated right ventricular systolic pressure (RVSP) >40 mmHg; RVSP/systemic systolic blood pressure (SBP) ratio >0.5; Presence of ventricular septal wall flattening	at 28 days of life
Primary	Presence of pulmonary hypertension	Pulmonary hypertension will be defined as one or more of the following echocardiographic findings: Presence of a cardiac shunt with bidirectional or right-to-left flow; Estimated right ventricular systolic pressure (RVSP) >40 mmHg; RVSP/systemic systolic blood pressure (SBP) ratio >0.5; Presence of ventricular septal wall flattening	at 36 weeks PMA
Primary	Presence of pulmonary hypertension	Pulmonary hypertension will be defined as one or more of the following echocardiographic findings: Presence of a cardiac shunt with bidirectional or right-to-left flow; Estimated right ventricular systolic pressure (RVSP) >40 mmHg; RVSP/systemic systolic blood pressure (SBP) ratio >0.5; Presence of ventricular septal wall flattening	at 6 months of age
Primary	Presence of pulmonary hypertension	Pulmonary hypertension will be defined as one or more of the following echocardiographic findings: Presence of a cardiac shunt with bidirectional or right-to-left flow; Estimated right ventricular systolic pressure (RVSP) >40 mmHg; RVSP/systemic systolic blood pressure (SBP) ratio >0.5; Presence of ventricular septal wall flattening	at 12 months of age
Secondary	Presence of bronchopulmonary dysplasia	Assessment of supplemental oxygen	at 28 days of life
Secondary	Presence of bronchopulmonary dysplasia	Classification of BPD with an oxygen reduction test	at 36 weeks PMA
Secondary	Birth weight	Birth weight in grams	at birth
Secondary	Gestational age	Gestational age in weeks	at birth
Secondary	Small for gestational age	Birth weight	at birth
Secondary	Oligohydramnios	Presence of oligohydramnios during pregnancy	at birth
Secondary	Maternal hypertensive disorders	Presence of maternal hypertensive disorders during pregnancy (pre-eclampsia, hypertension, HELLP)	at birth
Secondary	ROP	Presence of retinopathy of prematurity	at 36 weeks
Secondary	NEC	Presence of necrotizing enterocolitis	at 36 weeks
Secondary	PDA	Presence of patent ductus arteriosus	at 36 weeks
Secondary	Sepsis	Presence of sepsis	up to discharge from the NICU, an average of 16 weeks
Secondary	VAP	Presence of ventilator associated pneumonia	at 36 weeks