Clinical Trial: Management of Hypotension In the Preterm Infant

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Management of Hypotension In Preterm Infants: The HIP Trial Protocol for a Randomized Controlled Trial of Hypotension Management in the Extremely Low Gestational Age Newborn

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.


Detailed Summary:

While hypotension - low blood pressure (BP) - is commonly diagnosed and treated in the very preterm infant there is enormous variation in clinical practice.Hypotension is statistically associated with adverse short-term and long-term outcomes however a systematic review of the literature was unable to find clear criteria to define hypotension. In addition the evidence to support current management strategies is minimal and mostly dependent on small studies that have measured short-term physiologic endpoints. Preterm infants who are diagnosed with and treated for low BP often have no biochemical or clinical signs of shock, they may have normal systemic blood flow, low systemic vascular resistance, and adequate tissue oxygen delivery and probably do not require treatment. Careful observation of such infants without intervention approach previously coined "permissive hypotension" may well be appropriate.

Excessive intervention in preterm infants may be unnecessary or even harmful. Analysis of a large neonatal database (Canadian Neonatal Network, CNN) demonstrated that treatment of hypotension was associated with an increase in serious brain injury. This remained true even after mean BP was included in the regression model suggesting that it may be the treatment of hypotension rather than the presence of hypotension which is harmful. The most common approach to treatment is to give one or more fluid boluses followed by dopamine. However, observational data have shown an association of fluid bolus administration with intracranial bleeding and in animal models correction of hypotension by rapid volume infusion can result in intraventricular haemorrhage; a complication which is associated with increased rates of death and neurosensory impairment in preterm human infants. Fluctuations in BP following commencement of inotropes are well recognised and could also trigger i
Sponsor: University College Cork

Current Primary Outcome:

  • First Co-Primary Outcome Measure: Survival to 36 weeks postmenstrual age free of severe brain injury [ Time Frame: 36 weeks ]
    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.
  • Second Co-Primary Outcome Measure: Survival without moderate or serious disability as defined using consensus criteria for neurodevelopmental impairment. [ Time Frame: 2 years of age ]
    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).


Original Primary Outcome: Survival to 36 weeks gestational age free of severe brain injury on cranial ultrasound at or nearest 36 weeks [ Time Frame: 2 years corrected gestational age ]

A composite primary outcome, of survival to 36 weeks gestational age free of severe brain injury (moderate or severe ventricular dilatation, intracerebral echodense lesions, and cystic periventricular leukomalacia) on cranial ultrasound at or nearest 36 weeks. It is important to combine these two outcome components because early death may preclude the formal diagnosis of IVH. It is a standard composite, dichotomous outcome.


Current Secondary Outcome: All cause mortality at 36 weeks gestational age [ Time Frame: 36 weeks gestational age ]

Original Secondary Outcome: Same as current

Information By: University College Cork

Dates:
Date Received: November 27, 2011
Date Started: January 2015
Date Completion: January 2018
Last Updated: January 27, 2015
Last Verified: January 2015