Hypotension in Preterm Infants (HIP) randomised trial

Eugene M Dempsey, Keith J Barrington, Neil Marlow, Colm Patrick Finbarr O'Donnell, Jan Miletin, Gunnar Naulaers, Po-Yin Cheung, John David Corcoran, Afif Faisal El-Khuffash, Geraldine B Boylan, Vicki Livingstone, Gerard Pons, Jozef Macko, David Van Laere, Hana Wiedermannova, Zbyněk Straňák, HIP consortium, Eugene M Dempsey, Keith J Barrington, Neil Marlow, Colm Patrick Finbarr O'Donnell, Jan Miletin, Gunnar Naulaers, Po-Yin Cheung, John David Corcoran, Afif Faisal El-Khuffash, Geraldine B Boylan, Vicki Livingstone, Gerard Pons, Jozef Macko, David Van Laere, Hana Wiedermannova, Zbyněk Straňák, HIP consortium

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.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Trial design flow diagram. BP, blood pressure; GA, gestational age.
Figure 2
Figure 2
CONSORT diagram. CONSORT, Consolidated Standards of Reporting Trials.
Figure 3
Figure 3
Changes in MBP over time by group. MBP, mean blood pressure.

References

    1. Rabe H, Rojas-Anaya H. Inotropes for preterm babies during the transition period after birth: friend or foe? Arch Dis Child Fetal Neonatal Ed 2017;102:F547–50. 10.1136/archdischild-2016-311709
    1. Cox DJ, Groves AM. Inotropes in preterm infants--evidence for and against. Acta Paediatr 2012;101:17–23. 10.1111/j.1651-2227.2011.02545.x
    1. Dempsey EM, Barrington KJ. Treating hypotension in the preterm infant: when and with what: a critical and systematic review. J Perinatol 2007;27:469–78. 10.1038/sj.jp.7211774
    1. Batton B, Li L, Newman NS, et al. . Use of antihypotensive therapies in extremely preterm infants. Pediatrics 2013;131:e1865–73. 10.1542/peds.2012-2779
    1. Dempsey EM, Barrington KJ, Marlow N, et al. . Management of hypotension in preterm infants (the hip trial): a randomised controlled trial of hypotension management in extremely low gestational age newborns. Neonatology 2014;105:275–81. 10.1159/000357553
    1. Dempsey EM, Barrington KJ. Diagnostic criteria and therapeutic interventions for the hypotensive very low birth weight infant. J Perinatol 2006;26:677–81. 10.1038/sj.jp.7211579
    1. Sehgal A, Osborn D, McNamara PJ. Cardiovascular support in preterm infants: a survey of practices in Australia and New Zealand. J Paediatr Child Health 2012;48:317–23. 10.1111/j.1440-1754.2011.02246.x
    1. Batton B, Batton D, Riggs T. Blood pressure during the first 7 days in premature infants born at postmenstrual age 23 to 25 weeks. Am J Perinatol 2007;24:107–15. 10.1055/s-2007-970178
    1. Laughon M, Bose C, Allred E, et al. . Factors associated with treatment for hypotension in extremely low gestational age newborns during the first postnatal week. Pediatrics 2007;119:273–80. 10.1542/peds.2006-1138
    1. Stranak Z, Semberova J, Barrington K, et al. . International survey on diagnosis and management of hypotension in extremely preterm babies. Eur J Pediatr 2014;173:793–8. 10.1007/s00431-013-2251-9
    1. Subhedar NV, Shaw NJ. Dopamine versus dobutamine for hypotensive preterm infants. Cochrane Database Syst Rev 2000;2:CD001242. 10.1002/14651858.CD001242
    1. Faust K, Härtel C, Preuß M, et al. . Short-term outcome of very-low-birthweight infants with arterial hypotension in the first 24 h of life. Arch Dis Child Fetal Neonatal Ed 2015;100:F388–92. 10.1136/archdischild-2014-306483
    1. Batton B, Li L, Newman NS, et al. . Early blood pressure, antihypotensive therapy and outcomes at 18-22 months' corrected age in extremely preterm infants. Arch Dis Child Fetal Neonatal Ed 2016;101:F201–6. 10.1136/archdischild-2015-308899
    1. Barrington KJ, Dempsey EM. Cardiovascular support in the preterm: treatments in search of indications. J Pediatr 2006;148:289–91. 10.1016/j.jpeds.2005.12.056
    1. Dempsey EM, Al Hazzani F, Barrington KJ. Permissive hypotension in the extremely low birthweight infant with signs of good perfusion. Arch Dis Child Fetal Neonatal Ed 2009;94:F241–4. 10.1136/adc.2007.124263
    1. Watterberg KL, Fernandez E, Walsh MC, et al. . Barriers to enrollment in a randomized controlled trial of hydrocortisone for cardiovascular insufficiency in term and late preterm newborn infants. J Perinatol 2017;37:1220–3. 10.1038/jp.2017.131
    1. Batton BJ, Li L, Newman NS, et al. . Feasibility study of early blood pressure management in extremely preterm infants. J Pediatr 2012;161:65–9. 10.1016/j.jpeds.2012.01.014
    1. Steinhorn RH, Fineman J, Kusic-Pajic A, et al. . Bosentan as adjunctive therapy for persistent pulmonary hypertension of the newborn: results of the randomized multicenter placebo-controlled exploratory trial. J Pediatr 2016;177:90–6. 10.1016/j.jpeds.2016.06.078
    1. Gagliardi L. Treatment of hypotension in preterm infants: pathophysiology versus evidence-based medicine. Acta Paediatr 2013;102:446–8. 10.1111/apa.12190
    1. Padbury JF. Gasping for air. J Pediatr 2016;177:2–3. 10.1016/j.jpeds.2016.08.038
    1. Dempsey EM, Connolly K. Who are the PDCO? Eur J Pediatr 2014;173:233–5. 10.1007/s00431-013-2096-2
    1. Bravo MC, López-Ortego P, Sánchez L, et al. . Randomized, placebo-controlled trial of dobutamine for low superior vena cava flow in infants. J Pediatr 2015;167:572–8. 10.1016/j.jpeds.2015.05.037
    1. Durrmeyer X, Marchand-Martin L, Porcher R, et al. . Abstention or intervention for isolated hypotension in the first 3 days of life in extremely preterm infants: association with short-term outcomes in the EPIPAGE 2 cohort study. Arch Dis Child Fetal Neonatal Ed 2017;102:490–6. 10.1136/archdischild-2016-312104
    1. Barrington KJ, Stewart S, Lee S. Differing blood pressure thresholds in preterm infants, effects on frequency of diagnosis of hypotension and intraventricular haemorrhage. Pediatr Res 2002;51:455A.
    1. Tarnow-Mordi W, Morris J, Kirby A, et al. . Delayed versus immediate cord clamping in preterm infants. N Engl J Med 2017;377:2445–55. 10.1056/NEJMoa1711281
    1. Katheria AC, Lakshminrusimha S, Rabe H, et al. . Placental transfusion: a review. J Perinatol 2017;37:105-111. 10.1038/jp.2016.151
    1. Popat H, Robledo KP, Kirby A, et al. . Associations of measures of systemic blood flow used in a randomized trial of delayed cord clamping in preterm infants. Pediatr Res 2019;86:71–6. 10.1038/s41390-019-0348-1
    1. Göpel W, Kribs A, Ziegler A, et al. . Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised, controlled trial. Lancet 2011;378:1627–34. 10.1016/S0140-6736(11)60986-0
    1. Azzopardi D, Brocklehurst P, Edwards D, et al. . The TOBY study. whole body hypothermia for the treatment of perinatal asphyxial encephalopathy: a randomised controlled trial. BMC Pediatr 2008;8:17. 10.1186/1471-2431-8-17
    1. Rich WD, Auten KJ, Gantz MG, et al. . Antenatal consent in the support trial: challenges, costs, and representative enrollment. Pediatrics 2010;126:e215–21. 10.1542/peds.2009-3353

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