Study of Dopamine Versus Vasopressin for Treatment of Low Blood Pressure in Low Birth Weight Infants

Study Overview
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Brief Summary
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Low blood pressure or hypotension is a very important problem that is often seen in premature babies, especially those with low birth weight. Severe hypotension leads to significant problems including brain bleeds, developmental delays, kidney and liver problems, and other issues that can affect babies for the rest of their lives. An important aspect in the management of infants with hypotension is the decision of when to treat and with what agent. Research is being conducted to try to find the best medication to use in these situations. Dopamine is often used first, but it does not always prove to be effective, and it has several concerning side effects. This study will look at vasopressin, which has fewer side effects, as a first-line medication for low blood pressure in extremely low birth weight infants. Hypotheses and Specific Aims: This study will show superiority of vasopressin to dopamine in preterm, extremely low birth weight infants who have hypotension within the first 24 hours of life. We will specifically look at its ability to raise blood pressure values, improve clinical symptoms seen, any adverse effects, and clinical outcomes of babies being treated.

Detailed Description
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Hypotension in the low birth weight (LBW) and extremely low birth weight (ELBW) infant is often encountered in the postnatal adaptation phase. Severe, prolonged hypotension contributes to cellular dysfunction and cell death. Systemic hypotension affects close to half of all ELBW infants and a significant portion of LBW infants. The true definition of hypotension remains to be a question. There is a linear association between birth weight, gestational age, and mean blood pressure but blood pressure can vary significantly in the first day of life. The critical period tends to be the first 24-36 hours of life as blood pressure tends to rise significantly in the first 72 hours of life regardless of gestational age. Preterm infants suffering from hypotension have a higher incidence and increased severity of intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), and long-term neurodevelopmental sequelae compared to normotensive preterm infants. Effects on other organ systems can result in renal injury, hepatic injury, and the development of necrotizing enterocolitis among other complications. An important aspect in the management of infants with hypotension is the decision of when to treat and with what agent. Dopamine is commonly used as first-line therapy, but issues with efficacy and its side effect profile have lessened its favorability over the years. Few studies compare dopamine to other agents as a first -line treatment. This study hopes to contribute to the literature information on vasopressin as a potential first-line agent for treatment of neonatal hypotension in low birth weight infants.

Official Title
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Dopamine Versus Vasopressin for Cardiovascular Support in Extremely Low Birth Weight Infants: A Randomized, Blinded Pilot Study

Conditions
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Hypotension

Intervention / Treatment
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* Drug: Dopamine
* Drug: Arginine Vasopressin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants less than 24 hours of age Infants with birth weight of <1001 grams and/or gestational age of <29 weeks Not initiated on any continuous pressor therapy prior to enrollment Intravenous line in place Outborn infants meeting eligibility criteria Exclusion Criteria: Infants not meeting eligibility criteria Infants with life-threatening congenital defects Infants with congenital hydrops Infants with frank hypovolemia (perinatal history consistent with decreased circulating blood volume plus clinical signs of hypovolemia) Infants with other unresolved causes of hypotension (air leaks, lung overdistention, or metabolic abnormalities).

Ages Eligible for Study
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Maximum Age: 24 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dopamine treatment<br>Dopamine treatment beginning at 5 mcg/kg/min and titrated by 5 mcg/kg/min to effect up to maximum of 20 mcg/kg/min | Drug: Dopamine<br>* dopamine at low/medium/and high dose (5, 10, 15, and 20 mcg/kg/min) given IV as a continuous infusion, titrated up for efficacy<br>* Other names: Dopamine Hydrochloride;|
| Active Comparator: Vasopressin treatment<br>Arginine Vasopressin treatment beginning at 0.01 units/kg/hr and titrated up by 0.01 units/kg/hr to effect up to a maximum of 0.04 units/kg/hr | Drug: Arginine Vasopressin<br>* vasopressin at low/medium/and high dose (0.01, 0.02, 0.03, or 0.04 units/kg/hr) given IV as a continuous infusion, titrated up for efficacy<br>* Other names: Argipressin;|
| No Intervention: Comparison Arm<br>Infants who did not require vasopressor support for hypotension during the first 24 hours of life | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects in Each Group Who Have Achieved an Optimal Mean Blood Pressure Value at 24 Hours of Life | Optimal mean blood pressure (OMBP) will be defined as either a 10% increase in mean blood pressure value or a 2-3 mmHg rise in mean blood pressure value AND an improvement in tissue perfusion as demonstrated by a resolution in the specified clinical symptom (designated upon enrollment) within 4-6 hours of having reached OMBP | 24 hours of life | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart Rate Change From Baseline | Heart rate change from baseline during study drug administration | 96 hours or until hypotension completely resolved and medications stopped | 
| Acid-base Status |  | 96 hours or until hypotension resolved and medication completely stopped | 
| Hyponatremia |  | 96 hours or until medication completely stopped | 
| Urine Output |  | 96 hours or until hypotension resolved and medication completely stopped | 
| Evidence of Ischemic Changes | Physical examinations were done on at least a twice daily basis to evaluate for any ischemic lesions (especially on the limbs) of all subjects. The presence of any lesion considered to be due to ischemia would have been reported in this data. | 96 hours or until medication completely stopped | 
| Necrotizing Enterocolitis |  | until hospital discharge, up to 12 weeks | 
| Ventilator Days |  | Until hospital discharge, up to 15 months | 
| Presence of Patent Ductus Arteriosus (PDA) |  | until hospital discharge, up to 12 weeks | 
| Grade 3 Intraventricular Hemorrhage or Worse on Head Ultrasound |  | Until hospital discharge, up to 15 months | 
| Retinopathy of Prematurity Stage 3 or Higher | All subjects were followed by an ophthalmologist with initial exam at 4-6 weeks of age. The Stages describe the ophthalmoscopic findings at the junction between the vascularized and avascular retina. Each subject is followed until cleared by ophthalmology. For this outcome measure, the most severe stage of disease was used in analysis. Stage 1 is a faint demarcation line. Stage 2 is an elevated ridge. Stage 3 is extraretinal fibrovascular proliferation (neovascularization). Stage 4 is sub-total retinal detachment. Stage 5 is total retinal detachment. Stages 1 and 2 do not lead to blindness. However, they can progress to the more severe stages. | Until hospital discharge, up to 15 months | 
| Presence of Bronchopulmonary Dysplasia (BPD) | Infants were evaluated for oxygen need at 36 weeks postmenstrual age. If they required supplemental oxygen, they were diagnosed with BPD | 36 weeks postmenstrual age | 
| All Cause Mortality |  | admission to hospital discharge, up to 15 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypotension, Low blood pressure, Neonate, Dopamine, Vasopressin, Extremely Low Birth Weight Infant