Dopamine vs. Norepinephrine for Hypotension in Neonates With Pulmonary Hypertension (DONE)

University of California (UC) Davis

Status and phase: Enrolling; Phase 4

Conditions: Pulmonary Hypertension of the Newborn (PPHN); Hypoxemic Respiratory Failure; Hypotension and Shock

Treatments: Drug: Dopamine administration; Drug: Norepinephrine

Study type: Interventional

Funder types: Other

Identifiers

NCT07322133

23394282

GFDS25 (Other Grant/Funding Number)

Details and patient eligibility

About

This pilot randomized clinical trial compares dopamine and norepinephrine as first-line vasoactive therapies in term and late preterm neonates with pulmonary hypertension associated with hypoxemic respiratory failure and systemic hypotension. Systemic hypotension is a common and clinically significant complication of persistent pulmonary hypertension of the newborn (PPHN) and frequently requires vasopressor support to maintain adequate systemic perfusion. Dopamine is commonly used in this setting; however, prior animal experimental and clinical data suggest it may increase pulmonary vascular resistance, potentially worsening right ventricular afterload and hypoxemia. Norepinephrine may preferentially increase systemic vascular resistance with less effect on the pulmonary circulation. This study evaluates short-term hemodynamic and oxygenation responses following initiation of dopamine or norepinephrine.

Full description

Persistent pulmonary hypertension of the newborn (PPHN) is a serious cardiopulmonary disorder characterized by sustained elevation of pulmonary vascular resistance, leading to right-to-left shunting, impaired oxygenation, and increased morbidity and mortality. In addition to hypoxemic respiratory failure, many infants with PPHN develop systemic hypotension. Management of systemic hypotension in this population is complex, as vasoactive medications may have differing effects on systemic and pulmonary circulations.

Dopamine is widely used as first-line therapy for neonatal hypotension because of its dose-dependent dopaminergic and adrenergic effects. However, both animal models and clinical observations suggest that dopamine may increase pulmonary vascular resistance in neonates with PPHN. Norepinephrine, a predominantly alpha-adrenergic agonist with modest beta-adrenergic activity, may provide more selective augmentation of systemic vascular resistance while exerting less influence on pulmonary vascular tone. Despite the increasing clinical use of norepinephrine in neonatal intensive care units, there are no prospective trials comparing dopamine and norepinephrine in neonates with PPHN.

This is a single-center, cluster-randomized, pilot clinical trial enrolling term and late preterm neonates with hypoxemic respiratory failure, echocardiographic evidence of pulmonary hypertension, and systemic hypotension that persists despite initial fluid resuscitation. Eligible infants are assigned by time-based cluster randomization to receive either dopamine or norepinephrine as first-line vasoactive therapy, consistent with standard clinical practice in the neonatal intensive care unit. Informed consent is obtained for research-specific procedures, including serial targeted neonatal echocardiography, while vasoactive medication use follows established clinical protocols.

Enrollment: 30 estimated patients

Sex: All

Ages: Under 28 days old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Postmenstrual age > 34 6/7 weeks and Postnatal age ≤ 28 days
2. On respiratory support (Invasive mechanical ventilation, NIPPV, CPAP, HFNC ≥ 2 LPM) and FiO2 ≥ 0.3
3. Echocardiographic evidence of pulmonary hypertension
4. Mean arterial pressure below the threshold for gestational age despite a 10-20 mL/kg fluid bolus

Permissible Comorbidities: CDH, trisomy 21, HIE on hypothermia, PDA, PFO/ASD, VSD < 2 mm

Exclusion criteria

1. Gestational age < 32 weeks
2. Severe hypoxic respiratory failure (OI > 35 or SpO2 < 75% on 100% FiO2 for > 60 minutes)
3. Lethal anomalies (e.g., trisomy 13 or 18)
4. Complex congenital heart disease beyond specified criteria

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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30 participants in 2 patient groups

Dopamine Arm

Active Comparator group

Description:

Infants in this group will receive dopamine as their first-line vasopressor. Continuous intravenous dopamine infusion will be initiated at 5 mcg/kg/min and titrated to achieve gestational age appropriate mean arterial blood pressure targets (maximum 20 mcg/kg/min).

Treatment:

Drug: Dopamine administration

Norepinephrine Arm

Active Comparator group

Description:

Infants in this group will receive norepinephrine as their first-line vasopressor. Continuous intravenous norepinephrine infusion initiated at 0.02 mcg/kg/min and titrated to achieve gestational age appropriate mean arterial blood pressure targets (maximum 1 mcg/kg/min).

Treatment:

Drug: Norepinephrine