Management of Hypotension In the Preterm Infant

NCT01482559 | Terminated Phase 3 DMC

• 2 other identifiers: HIP-FP7-BrePco2010-023988-17
• Study Type: interventional
• Target: 58
• Locations: 5 countries
• Sites: 10

Brief Summary

The HIP trial is a large pragmatic, multinational, randomised trial of two different strategies for the management of hypotension in extremely low gestational age newborns (Standard with dopamine versus a restricted with placebo approach). HYPOTHESIS: A restricted approach to the management of hypotension in extremely low gestational age newborns will result in improved neonatal and long-term developmental outcomes. PRIMARY OBJECTIVE: To determine whether a restricted approach to the management of hypotension compared to using dopamine as first line pressor agent in infants born less than 28 weeks of gestation within the first 72 hrs after birth (transitional period), improves survival without significant brain injury at 36 weeks postmenstrual age (PMA) and improves survival without moderate or severe neurodevelopmental disability at 2 years corrected age.

Conditions

Hypotension; Low Blood Pressure; Intraventricular Hemorrhage of Prematurity

Keywords

Dopamine; Intraventricular haemorrhage; Periventricular Leukomalacia; Neurodisability; Infant

Outcome Measures

Primary Outcomes (2)

• First Co-Primary Outcome Measure: Survival to 36 weeks postmenstrual age free of severe brain injury

  Survival to 36 weeks postmenstrual age free of severe brain injury (moderate or severe ventricular dilatation, intracerebral echodense lesions, and cystic periventricular leukomalacia) on cranial ultrasound at 36 weeks or discharge home which ever is the earlier.

  36 weeks

• Second Co-Primary Outcome Measure: Survival without moderate or serious disability as defined using consensus criteria for neurodevelopmental impairment.

  Families will be offered routine appointments as per the local follow-up system. At 12-months, the physician will complete a simple disability assessment and all surviving infants will have a locally performed formal neurodisability assessment at 24 months age corrected for weeks of prematurity defined using criteria set out in the consensus statement "Health status...." (ww bapm.org/publications).

  2 years of age

Secondary Outcomes (1)

• All cause mortality at 36 weeks gestational age

  36 weeks gestational age

Study Arms (2)

dextrose 5%

PLACEBO COMPARATOR

IV Infusion

Drug: Dextrose 5%

Dopamine Hydrochloride

EXPERIMENTAL

IV Infusion

Drug: Dopamine hydrochloride

Interventions

Dopamine hydrochloride DRUG

Active drug substance 1.5 mg in 1 mL IV Infusion Minimum dose = 5mcg/kg/min Maximum dose = 20mcg/kg/min

Also known as: ATC Code: C01CA04

Dopamine Hydrochloride

Dextrose 5% DRUG

IV Infusion Minimum dose = 5mcg/kg/min Maximum dose = 20mcg/kg/min

Also known as: Placebo

dextrose 5%

Eligibility Criteria

• Age: 23 Weeks - 27 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Gestational age at birth less than 28 completed weeks, i.e. up to and including 27 weeks and 6 days.
• Within 72 hours of birth
• An indwelling arterial line, either umbilical or peripheral (e.g. radial, posterior tibial), suitably calibrated and zeroed, to monitor BP with the measuring dome at the level of the infant's mid-axillary line when supine
• A pre-trial cerebral ultrasound scan demonstrating no evidence of grade 3 or 4 haemorrhage intraventricular haemorrhage (IVH)(i.e. intraparenchymal echodensity or echolucency, with or without acquired cerebral ventriculomegaly)
• A mean blood pressure 1 mmHg or more below a mean BP value equivalent to the gestational age in completed weeks, which persists over a 15 minute period (mean BP \< gestational age)

You may not qualify if:

• Considered non-viable by attending clinicians.
• Life-threatening congenital abnormalities including congenital heart disease (excluding patent ductus arteriosus, small atrial and/or ventricular septal defect). Infants known to require surgical treatment e.g. congenital diaphragmatic hernia, trache-oesophageal fistula, omphalocele, gastroschisis. Neuromuscular disorders. Frank hypovolaemia. Hydrops Fetalis.
• Cranial ultrasound abnormality grade 3 IVH or more prior to enrolment

Sponsors & Collaborators

• University College Cork: lead
• Cork University Hospital: collaborator
• Coombe Women and Infants University Hospital: collaborator
• Royal College of Surgeons, Ireland: collaborator
• National Maternity Hospital, Ireland: collaborator
• University Hospital, Antwerp: collaborator
• KU Leuven: collaborator
• University of Alberta: collaborator
• St. Justine's Hospital: collaborator
• Institute for the Care of Mother and Child, Prague, Czech Republic: collaborator
• GABO:mi: collaborator
• BrePco Biopharma Limited: collaborator
• University College, London: collaborator
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator
• Clininfo S.A.: collaborator

Study Sites (10)

University Hospital Antwerp

Antwerp, Edegem, B-2650, Belgium

Location

Katholieke Universiteit Leuven

Oude God, Leuven, 3000, Belgium

Location

University of Alberta

Edmonton, Alberta, T6G 2R3, Canada

Location

Centre hospitalier universitaire Sainte-Justine

Montreal, Quebec, H1T 1C9, Canada

Location

Univerzita Karlova v Praze

Prague, 11636, Czechia

Location

Coombe Women and Infants University Hospital

Dublin, Dublin, 8, Ireland

Location

Cork University Maternity Hospital

Cork, Ireland

Location

Royal College of Surgeons in Ireland

Dublin, Ireland

Location

University College Dublin

Dublin, Ireland

Location

Royal Maternity Hospital

Belfast, BT12 6BA, United Kingdom

Location

Related Publications (1)

• Dempsey EM, Barrington KJ, Marlow N, O'Donnell CPF, Miletin J, Naulaers G, Cheung PY, Corcoran JD, El-Khuffash AF, Boylan GB, Livingstone V, Pons G, Macko J, Van Laere D, Wiedermannova H, Stranak Z; HIP consortium. Hypotension in Preterm Infants (HIP) randomised trial. Arch Dis Child Fetal Neonatal Ed. 2021 Jul;106(4):398-403. doi: 10.1136/archdischild-2020-320241. Epub 2021 Feb 24.

  PMID: 33627329 DERIVED

MeSH Terms

Conditions

Hypotension; Leukomalacia, Periventricular

Interventions

Dopamine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Encephalomalacia; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Biogenic Monoamines; Biogenic Amines; Amines; Organic Chemicals; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Eugene Dempsey

  University College Cork

  STUDY DIRECTOR

• Peter Filan

  Cork University Maternity Hospital

  PRINCIPAL INVESTIGATOR

• Gunnar Naulaers

  KU Leuven

  PRINCIPAL INVESTIGATOR

• Zybnek Stranak

  Univerzita Karlova v Praze

  PRINCIPAL INVESTIGATOR

• Keith Barrington

  St. Justine's Hospital

  PRINCIPAL INVESTIGATOR

• Colm O Donnell

  University College Dublin

  PRINCIPAL INVESTIGATOR

• Jan Miletin

  Coombe Women and Infants University Hospital

  PRINCIPAL INVESTIGATOR

• Po-Yin Cheung

  University of Alberta

  PRINCIPAL INVESTIGATOR

• David Corcoran

  Royal College of Surgeons in Ireland

  PRINCIPAL INVESTIGATOR

• Neil Marlow

  University College, London

  PRINCIPAL INVESTIGATOR

• Gerard Pons

  Institut National de la Santé Et de la Recherche Médicale, France

  PRINCIPAL INVESTIGATOR

• David Van Laere

  Neonatale Intensieve Zorgen

  PRINCIPAL INVESTIGATOR

• David Millar

  Royal Maternity Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Eugene Dempsey, Consultant Neonatologist

Study Record Dates

• First Submitted: November 27, 2011
• First Posted: November 30, 2011
• Study Start: February 1, 2015
• Primary Completion: September 1, 2017
• Study Completion: October 1, 2019
• Last Updated: October 2, 2019

Record last verified: 2019-09

Locations

BE (2); IE (4); CZ (1); GB (1); CA (2)