Hypotension and ShockPhase 4DONENCT07322133
Dopamine vs. Norepinephrine for Hypotension in Neonates With Pulmonary Hypertension (DONE)
A Phase 4 study testing Dopamine administration and Norepinephrine in people with Hypotension and Shock and Pulmonary Hypertension of the Newborn (PPHN), run by University of California, Davis at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages Up to 28 days
- Conditions the study is for
- Hypotension and Shock, Pulmonary Hypertension of the Newborn (PPHN), Hypoxemic Respiratory Failure
- What is being tested?
- Dopamine administration and Norepinephrine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Oct 2026to 30 Jun 2027
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 28 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Postmenstrual age > 34 6/7 weeks and Postnatal age ≤ 28 days
- On respiratory support (Invasive mechanical ventilation, NIPPV, CPAP, HFNC ≥ 2 LPM) and FiO2 ≥ 0.3
- Echocardiographic evidence of pulmonary hypertension
- 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
Who cannot join
- Gestational age < 32 weeks
- Severe hypoxic respiratory failure (OI > 35 or SpO2 < 75% on 100% FiO2 for > 60 minutes)
- Lethal anomalies (e.g., trisomy 13 or 18)
- Complex congenital heart disease beyond specified criteria
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
UC Davis Children's Hospital
Sacramento, California, 95817
Solomon Tatagiri, MBBS, 916-734-8672, solomontp@gmail.com
Deepika Sankaran, MD, 916-734-8672, dsankaran@health.ucdavis.edu
About this study
Official title: Dopamine vs. Norepinephrine in Term and Late Preterm Neonates With Hypoxemic Respiratory Failure and Systemic Hypotension Due to Pulmonary Hypertension: A Pilot Trial
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.
Read the detailed 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.
- Conditions
- Hypotension and Shock, Pulmonary Hypertension of the Newborn (PPHN), Hypoxemic Respiratory Failure
- Being tested
- Dopamine administration, Norepinephrine
- Keywords
- Pulmonary Hypertension, Systemic Hypotension, Vasopressor
- Medical subject headings
- Hypotension, Shock, Respiratory Insufficiency, Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dopamine administrationDrug
Infants meeting the inclusion criteria who are randomized to dopamine arm will receive dopamine infusion starting at 5 mcg/kg/min, titrated to mean arterial pressure targets based on gestational age, max dose 20 mcg/kg/min.
NorepinephrineDrug
Infants meeting the inclusion criteria who are randomized to norepinephrine arm will receive norepinephrine infusion starting at 0.02 mcg/kg/min, titrated to mean arterial pressure targets based on gestational age, max dose 1 mcg/kg/min.
| Study group | Role | What they receive |
|---|---|---|
| Dopamine Arm | Active comparator | 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). Receives: Drug: Dopamine administration |
| Norepinephrine Arm | Active comparator | 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). Receives: Drug: Norepinephrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
SAP/PAP ratio
Ratio of systemic arterial pressure to pulmonary arterial pressure (SAP/PAP)
Measured: Within 30 hours of vasopressor initiation.
LV Cardiac output
Left Ventricular Cardiac Output calculated with echocardiography
Measured: Within 30 hours of vasopressor initiation
Oxygenation Indices
FiO₂ (fraction of inspired oxygen), SpO₂ (peripheral oxygen saturation), PaO₂ (arterial oxygen partial pressure), OI (oxygenation index), OSI (oxygen saturation index)
Measured: Within 30 hours of vasopressor initiation
Secondary outcomes (3)
Use of inhaled nitric oxide (iNO)
Measured: Within 30 hours of vasopressor initiation
Need for additional vasoactive agents
Measured: Within 30 hours of vasopressor initiation
Echocardiographic markers of heart function
Right ventricle and Left ventricle function
Measured: Within 30 hours of vasopressor initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2026
- Study start30 Oct 2026 (estimated)
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Hypotension and ShockStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Miracle Network
- Responsible party
- Sponsor
- Investigators
- Deepika Sankaran, MD, Principal investigator, UC Davis Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07322133
- Sponsor's protocol ID
- 2339428
- Other IDs
- GFDS25
- Acronym
- DONE
- Status last verified
- Aug 2026
- First submitted
- 5 Jan 2026
- Last updated
- 18 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Jain A, El-Khuffash AF, van Herpen CH, Resende MHF, Giesinger RE, Weisz D, Mertens L, Jankov RP, McNamara PJ. Cardiac Function and Ventricular Interactions in Persistent Pulmonary Hypertension of the Newborn. Pediatr Crit Care Med. 2021 Feb 1;22(2):e145-e157. doi: 10.1097/PCC.0000000000002579.
PubMed 33044416Lesneski AL, Vali P, Hardie ME, Lakshminrusimha S, Sankaran D. Randomized Trial of Oxygen Saturation Targets during and after Resuscitation and Reversal of Ductal Flow in an Ovine Model of Meconium Aspiration and Pulmonary Hypertension. Children (Basel). 2021 Jul 14;8(7):594. doi: 10.3390/children8070594.
PubMed 34356574Siefkes HM, Lakshminrusimha S. Management of systemic hypotension in term infants with persistent pulmonary hypertension of the newborn: an illustrated review. Arch Dis Child Fetal Neonatal Ed. 2021 Jul;106(4):446-455. doi: 10.1136/archdischild-2020-319705. Epub 2021 Jan 21.
PubMed 33478959Lakshminrusimha S. The pulmonary circulation in neonatal respiratory failure. Clin Perinatol. 2012 Sep;39(3):655-83. doi: 10.1016/j.clp.2012.06.006.
PubMed 22954275Tourneux P, Rakza T, Bouissou A, Krim G, Storme L. Pulmonary circulatory effects of norepinephrine in newborn infants with persistent pulmonary hypertension. J Pediatr. 2008 Sep;153(3):345-9. doi: 10.1016/j.jpeds.2008.03.007. Epub 2008 May 12.
PubMed 18534241Steinhorn RH. Neonatal pulmonary hypertension. Pediatr Crit Care Med. 2010 Mar;11(2 Suppl):S79-84. doi: 10.1097/PCC.0b013e3181c76cdc.
PubMed 20216169Sankaran D, Lakshminrusimha S. Pulmonary hypertension in the newborn- etiology and pathogenesis. Semin Fetal Neonatal Med. 2022 Aug;27(4):101381. doi: 10.1016/j.siny.2022.101381. Epub 2022 Aug 7.
PubMed 35963740McNamara PJ, Giesinger RE, Lakshminrusimha S. Dopamine and Neonatal Pulmonary Hypertension-Pressing Need for a Better Pressor? J Pediatr. 2022 Jul;246:242-250. doi: 10.1016/j.jpeds.2022.03.022. Epub 2022 Mar 18. No abstract available.
PubMed 35314154Liet JM, Boscher C, Gras-Leguen C, Gournay V, Debillon T, Roze JC. Dopamine effects on pulmonary artery pressure in hypotensive preterm infants with patent ductus arteriosus. J Pediatr. 2002 Mar;140(3):373-5. doi: 10.1067/mpd.2002.123100.
PubMed 11953739Cheung PY, Barrington KJ. The effects of dopamine and epinephrine on hemodynamics and oxygen metabolism in hypoxic anesthetized piglets. Crit Care. 2001;5(3):158-66. doi: 10.1186/cc1016. Epub 2001 Apr 26.
PubMed 11353933Budniok T, ElSayed Y, Louis D. Effect of Vasopressin on Systemic and Pulmonary Hemodynamics in Neonates. Am J Perinatol. 2021 Oct;38(12):1330-1334. doi: 10.1055/s-0040-1712999. Epub 2020 Jun 2.
PubMed 32485754Shah S, Dhalait S, Fursule A, Khandare J, Kaul A. Use of Vasopressin as Rescue Therapy in Refractory Hypoxia and Refractory Systemic Hypotension in Term Neonates with Severe Persistent Pulmonary Hypertension-A Prospective Observational Study. Am J Perinatol. 2024 May;41(S 01):e886-e892. doi: 10.1055/a-1969-1119. Epub 2022 Oct 27.
PubMed 36302521McNamara PJ, Jain A, El-Khuffash A, Giesinger R, Weisz D, Freud L, Levy PT, Bhombal S, de Boode W, Leone T, Richards B, Singh Y, Acevedo JM, Simpson J, Noori S, Lai WW. Guidelines and Recommendations for Targeted Neonatal Echocardiography and Cardiac Point-of-Care Ultrasound in the Neonatal Intensive Care Unit: An Update from the American Society of Echocardiography. J Am Soc Echocardiogr. 2024 Feb;37(2):171-215. doi: 10.1016/j.echo.2023.11.016.
PubMed 38309835de Boode WP, Singh Y, Gupta S, Austin T, Bohlin K, Dempsey E, Groves A, Eriksen BH, van Laere D, Molnar Z, Nestaas E, Rogerson S, Schubert U, Tissot C, van der Lee R, van Overmeire B, El-Khuffash A. Recommendations for neonatologist performed echocardiography in Europe: Consensus Statement endorsed by European Society for Paediatric Research (ESPR) and European Society for Neonatology (ESN). Pediatr Res. 2016 Oct;80(4):465-71. doi: 10.1038/pr.2016.126. Epub 2016 Jun 8. No abstract available.
PubMed 27384404