Randomized Controlled Trial

. 2021 Jul;106(4):398-403.

doi: 10.1136/archdischild-2020-320241. Epub 2021 Feb 24.

Hypotension in Preterm Infants (HIP) randomised trial

Eugene M Dempsey¹, Keith J Barrington², Neil Marlow³, Colm Patrick Finbarr O'Donnell⁴, Jan Miletin⁵, Gunnar Naulaers⁶, Po-Yin Cheung⁷, John David Corcoran⁸, Afif Faisal El-Khuffash⁸, Geraldine B Boylan⁹, Vicki Livingstone⁹, Gerard Pons¹⁰, Jozef Macko¹¹, David Van Laere¹², Hana Wiedermannova¹³, Zbyněk Straňák¹⁴; HIP consortium

Affiliations

¹ Department of Paediatric and Child Health and INFANT Research Centre, University College Cork, Cork, Ireland g.dempsey@ucc.ie.
² Néonatologie, Centre Hospitalier Universitaire Sainte Justine, Montreal, Quebec, Canada.
³ Institute for Womens Health, University College London, London, UK.
⁴ Neonatal Intensive Care Unit, The National Maternity Hospital, Dublin, Ireland.
⁵ Paediatric and Newborn Medicine, Coombe Women and Infants University Hospital, Dublin, Ireland.
⁶ Neonatology, Katholieke Universiteit Leuven, Leuven, Belgium.
⁷ Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
⁸ Faculty of Medicine and Health Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland.
⁹ Department of Paediatric and Child Health and INFANT Research Centre, University College Cork, Cork, Ireland.
¹⁰ Clinical Pharmacology, Groupe Hospitalier Cochin-Broca, Hôtel Dieu, AP-HP, Paris, France.
¹¹ Department of Neonatology, Tomas Bata University in Zlin, Zlin, Zlínský Kraj, Czech Republic.
¹² NICU, UZ Antwerp, Edegem, Antwerp, Belgium.
¹³ Department of Pediatrics and Neonatal Care, Ostravska Univerzita, Ostrava, Moravskoslezský, Czech Republic.
¹⁴ Institute for the Care of Mother and Child, Third Faculty of Medicine, Charles University, Prague, Czech Republic.

PMID: 33627329
PMCID: PMC8237176
DOI: 10.1136/archdischild-2020-320241

Randomized Controlled Trial

Hypotension in Preterm Infants (HIP) randomised trial

Eugene M Dempsey et al. Arch Dis Child Fetal Neonatal Ed. 2021 Jul.

. 2021 Jul;106(4):398-403.

doi: 10.1136/archdischild-2020-320241. Epub 2021 Feb 24.

Authors

Affiliations

¹ Department of Paediatric and Child Health and INFANT Research Centre, University College Cork, Cork, Ireland g.dempsey@ucc.ie.
² Néonatologie, Centre Hospitalier Universitaire Sainte Justine, Montreal, Quebec, Canada.
³ Institute for Womens Health, University College London, London, UK.
⁴ Neonatal Intensive Care Unit, The National Maternity Hospital, Dublin, Ireland.
⁵ Paediatric and Newborn Medicine, Coombe Women and Infants University Hospital, Dublin, Ireland.
⁶ Neonatology, Katholieke Universiteit Leuven, Leuven, Belgium.
⁷ Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
⁸ Faculty of Medicine and Health Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland.
⁹ Department of Paediatric and Child Health and INFANT Research Centre, University College Cork, Cork, Ireland.
¹⁰ Clinical Pharmacology, Groupe Hospitalier Cochin-Broca, Hôtel Dieu, AP-HP, Paris, France.
¹¹ Department of Neonatology, Tomas Bata University in Zlin, Zlin, Zlínský Kraj, Czech Republic.
¹² NICU, UZ Antwerp, Edegem, Antwerp, Belgium.
¹³ Department of Pediatrics and Neonatal Care, Ostravska Univerzita, Ostrava, Moravskoslezský, Czech Republic.
¹⁴ Institute for the Care of Mother and Child, Third Faculty of Medicine, Charles University, Prague, Czech Republic.

PMID: 33627329
PMCID: PMC8237176
DOI: 10.1136/archdischild-2020-320241

Abstract

Objective: To determine whether restricting the use of inotrope after diagnosis of low blood pressure (BP) in the first 72 hours of life affects survival without significant brain injury at 36 weeks of postmenstrual age (PMA) in infants born before 28 weeks of gestation.

Design: Double-blind, placebo-controlled randomised trial. Caregivers were masked to group assignment.

Setting: 10 sites across Europe and Canada.

Participants: Infants born before 28 weeks of gestation were eligible if they had an invasive mean BP less than their gestational age that persisted for ≥15 min in the first 72 hours of life and a cerebral ultrasound free of significant (≥ grade 3) intraventricular haemorrhage.

Intervention: Participants were randomly assigned to saline bolus followed by either a dopamine infusion (standard management) or placebo (5% dextrose) infusion (restrictive management).

Primary outcome: Survival to 36 weeks of PMA without severe brain injury.

Results: The trial terminated early due to significant enrolment issues (7.7% of planned recruitment). 58 infants were enrolled between February 2015 and September 2017. The two groups were well matched for baseline variables. In the standard group, 18/29 (62%) achieved the primary outcome compared with 20/29 (69%) in the restrictive group (p=0.58). Additional treatments for low BP were used less frequently in the standard arm (11/29 (38%) vs 19/29 (66%), p=0.038).

Conclusion: Though this study lacked power, we did not detect major differences in clinical outcomes between standard or restrictive approach to treatment. These results will inform future studies in this area.

Trial registration number: NCT01482559, EudraCT 2010-023988-17.

Keywords: cardiology; neonatology; pharmacology.

PubMed Disclaimer

Conflict of interest statement

Competing interests: None declared.

Figures

**Figure 1**
Trial design flow diagram. BP, blood pressure; GA, gestational age.

**Figure 2**
CONSORT diagram. CONSORT, Consolidated Standards of Reporting Trials.

**Figure 3**
Changes in MBP over time by group. MBP, mean blood pressure.

See this image and copyright information in PMC

Comment in

When perfection is the enemy of good: EBM lessons from the HIP trial.
Carr CB, Ryan RM. Carr CB, et al. J Perinatol. 2023 Feb;43(2):253-256. doi: 10.1038/s41372-022-01554-8. Epub 2022 Nov 14. J Perinatol. 2023. PMID: 36376449 No abstract available.

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Evaluation of the Hypotensive Preterm Infant: Evidence-Based Practice at the Bedside?
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Blood pressure changes during the first 24 hours of life and the association with the persistence of a patent ductus arteriosus and occurrence of intraventricular haemorrhage.
Boldt R, Mäkelä PM, Immeli L, Sund R, Leskinen M, Luukkainen P, Andersson S. Boldt R, et al. PLoS One. 2021 Nov 30;16(11):e0260377. doi: 10.1371/journal.pone.0260377. eCollection 2021. PLoS One. 2021. PMID: 34847157 Free PMC article.

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References

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Hypotension in Preterm Infants (HIP) randomised trial

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Hypotension in Preterm Infants (HIP) randomised trial

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