Hypotension Clinical Trial
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
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.
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 intraventricular
haemorrhage. Furthermore dopamine the most commonly used inotrope has effects on many
physiologic functions including pituitary effects which lead to secondary hypothyroidism a
known risk factor for poor long-term neurodevelopmental outcome in the preterm infant. In
addition dopamine elevates BP in the newborn predominantly due to vasoconstriction, which may
be associated with a reduction in systemic perfusion.
There is no consensus on definitions of hypotension in the preterm infant. Many clinicians
rely on absolute BP values alone to guide intervention. BP reference ranges are often based
on birth weight, gestational age and postnatal age criteria. These statistically determined
values vary considerably being based on observations of BP made in small cohorts of infants
the majority of whom were born before the widespread implementation of important perinatal
interventions (e.g antenatal glucocorticoid therapy) which are known to improve outcome and
reduce the incidence of intraventricular haemorrhage in preterm infants. The Joint Working
Group of the British Association of Perinatal Medicine has recommended that the mean arterial
BP in mmHg should be maintained above the gestational age in weeks (e.g. an infant born at 25
weeks gestation should have a mean BP > 25mmHg). Despite little published evidence to support
this 'rule', it remains the most common criterion used to define hypotension and it has been
used in a number of recent randomised therapeutic intervention trials where it was the sole
entry criteria. However, Cunningham et al have shown a poor relationship between this
criterion and the incidence of intraventricular haemorrhage in preterm infants. In a separate
study, the CNN report that 52% of preterm infants with birth weight < 1500g have a mean
arterial BP less than their gestational age on the first day of life and thus may be
diagnosed with and treated for hypotension.
It is uncertain whether hypotension (however defined) results in adverse clinical outcomes
including adverse short-term outcomes (increased incidence of intraventricular haemorrhage)
and adverse long-term neurodevelopmental outcome. Furthermore it is unclear whether
intervention to treat hypotension results in improved outcomes. Dopamine is the most commonly
used agent, an endogenous catecholamine that causes vasoconstriction and elevates BP, but has
not been shown to improve clinical outcomes. Epinephrine is another endogenous catecholamine,
which at low to moderate doses causes vasodilatation and stimulates cardiac function. It may
increase perfusion when used in hypotensive neonates but the data are limited.
Current standard approaches to evaluation and treatment of transitional circulatory problems
in the preterm infant are not evidence based. It is essential that these approaches be
adequately investigated in this at risk group of infants.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT04062994 -
A Clinical Decision Support Trial to Reduce Intraoperative Hypotension
|
||
Active, not recruiting |
NCT02016599 -
Effects of Transitional Circulation in ELBW Infants
|
||
Recruiting |
NCT05836610 -
Hydrocortisone Therapy Optimization During Hypothermia Treatment in Asphyxiated Neonates
|
Phase 4 | |
Completed |
NCT03215797 -
Phenylephrine or Norepinephrine for a Better Hemodynamic Stability
|
Phase 3 | |
Suspended |
NCT02315937 -
Hemodynamic Assessment During Spinal Anesthesia Using Transthoracic Echocardiography'
|
N/A | |
Completed |
NCT02907931 -
Carotid Doppler Ultrasound for the Measurement of Intravascular Volume Status
|
N/A | |
Recruiting |
NCT02532270 -
Detecting Hypotension By Continuous Non-invasive Arterial Pressure Monitoring
|
N/A | |
Completed |
NCT02802683 -
Hemodynamic Impact of Hyperbaric Versus Isobaric for Spinal Anesthesia During Cesarean Delivery
|
Phase 4 | |
Completed |
NCT02437799 -
Dicrotic Notch and Hypotension at Caesarean Under Spinal Anaesthesia
|
N/A | |
Not yet recruiting |
NCT01941472 -
Transcutaneous pO2, Transcutaneous pCO2 and Central Venous pO2 Variations to Predict Fluid Responsiveness
|
N/A | |
Completed |
NCT02146898 -
The Severity Of Hypotension Comparing Three Positions During Spinal Anesthesia For Cesarean Delivery
|
N/A | |
Completed |
NCT01930227 -
Transcutaneous Electrical Acupoint Stimulation(TEAS) for Hypotension After Spinal Anesthesia in Parturients
|
N/A | |
Recruiting |
NCT01434251 -
Treatment of Hypotension of Prematurity (TOHOP)
|
N/A | |
Withdrawn |
NCT01183741 -
Accuracy of Non-Invasive Blood Pressure Measurement in Adults
|
Phase 3 | |
Completed |
NCT01592669 -
Passive Leg Raising Attenuates and Delays Tourniquet Deflation-induced Hypotension and Tachycardia
|
N/A | |
Completed |
NCT00991627 -
Different Approaches to Maternal Hypotension During Cesarean Section
|
Phase 4 | |
Withdrawn |
NCT00750516 -
Lactic Acid Levels In Hypotensive Patients Without(Standard) and With Tourniquet
|
||
Completed |
NCT00115726 -
Trial Assessing the Effect of Preoperative Furosemide on Intraoperative Blood Pressure
|
Phase 4 | |
Recruiting |
NCT05513066 -
Management Arterial Hypotension During Planned Caesarean Section, Intravenous Ephedrine/Phenylephrine Mixture Versus Intravenous Baby Noradrenaline
|
||
Completed |
NCT04089644 -
Manual vs Closed-loop Control of Mean Arterial Pressure
|
N/A |