Dose-finding for Dobutamine During Transitional Circulation in Very Preterm Infants (NeoCirc-002)

Dose-finding for Dobutamine During Transitional Circulation in the Very Preterm Infant

Single centre, dose finding trial to establish the minimum effective dose of dobutamine required to treat hemodynamic insufficiency, defined as low superior vena cava (SVC) flow, in infants below 33 weeks' gestation during transitional circulation (first 72 hours from birth).

Study Overview

• Status: Recruiting
• Conditions: Infant, Premature, Diseases; Circulatory and Respiratory Physiological Phenomena
• Intervention / Treatment: Drug: Intravenous dobutamine 5 mcg/kg/min; Drug: Intravenous dobutamine 7.5 mcg/kg/min; Drug: Intravenous dobutamine 10 mcg/kg/min; Drug: Intravenous dobutamine 12.5 mcg/kg/min; Drug: Intravenous dobutamine 15 mcg/kg/min

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Adelina Pellicer, MD; Phone Number: 917277416; Email: adelina.pellicer@salud.madrid.org

Study Locations

• Spain
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
    • Contact: María López, MD; Email: maríamaestro@gmail.com
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario La Paz
    • Contact: Adelina Pellicer, MD; Phone Number: 917277416; Email: adelina.pellicer@salud.madrid.org
  • Madrid, Spain, 28002
    • Recruiting
    • Hospital Universitario Quirónsalud
    • Contact: Fernando Cabañas, MD; Email: Fernando.cabanas@quironsalud.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Born with up to 32(+6) weeks gestation
• Presence of hemodynamic insufficiency, defined as SVC flow <51 ml/kg/min.
• Provision of signed and dated informed consent form by father/mother or legally designated representative, which can be given antenatally.

Exclusion Criteria:

• Neonates considered non-viable, with a clinical decision not to provide life support
• Infants with severe congenital hydrops fetalis needing chest or peritoneal drainage before recruitment
• Infants already on dobutamine treatment
• Infants with congenital malformations likely to affect cardiovascular adaptation (including: congenital diaphragmatic hernia, gastroschisis or congenital heart defects)
• Infants with chromosomal anomalies
• Lack of parental signed informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dobutamine dose A; Intravenous dobutamine will be administered at a dose of 5 mcg/kg/min. Weaning and stopping of the dobutamine infusion will be determined by the attending physician, following local policies.	Drug: Intravenous dobutamine 5 mcg/kg/min; Intravenous dobutamine will be administered at a dose of 5 mcg/kg/min.
Experimental: Dobutamine dose B; Intravenous dobutamine will be administered at a dose of 7.5 mcg/kg/min. Weaning and stopping of the dobutamine infusion will be determined by the attending physician, following local policies.	Drug: Intravenous dobutamine 7.5 mcg/kg/min; Intravenous dobutamine will be administered at a dose of 7.5 mcg/kg/min.
Experimental: Dobutamine dose C; Intravenous dobutamine will be administered at a dose of 10 mcg/kg/min. Weaning and stopping of the dobutamine infusion will be determined by the attending physician, following local policies.	Drug: Intravenous dobutamine 10 mcg/kg/min; Intravenous dobutamine will be administered at a dose of 10 mcg/kg/min.
Experimental: Dobutamine dose D; Intravenous dobutamine will be administered at a dose of 12.5 mcg/kg/min. Weaning and stopping of the dobutamine infusion will be determined by the attending physician, following local policies.	Drug: Intravenous dobutamine 12.5 mcg/kg/min; Intravenous dobutamine will be administered at a dose of 12.5 mcg/kg/min.
Experimental: Dobutamine dose E; Intravenous dobutamine will be administered at a dose of 15 mcg/kg/min. Weaning and stopping of the dobutamine infusion will be determined by the attending physician, following local policies.	Drug: Intravenous dobutamine 15 mcg/kg/min; Intravenous dobutamine will be administered at a dose of 15 mcg/kg/min.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimum dobutamine dose to reach and maintain a SVC flow above 55 ml/kg/min	Short-term pharmacodynamics (PD) endpoint: Minimum dobutamine dose to reach and maintain a superior vena cava (SVC) flow above 55 ml/kg/min on an echocardiogram performed at 1 and 3 hours after effective infusion of the allocated dose. The effective start of the infusion (t0) will be calculated as the time at which the infusion pump is switched on plus the empirical value for the interval arising from the dead space. We summarize t0 as "the time at which dobutamine is expected to reach the circulation"	1 and 3 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of neonates achieving and maintaining a clinically acceptable haemodynamic status	Proportion of neonates achieving and maintaining a clinically acceptable haemodynamic status with the dobutamine infusion alone in the first 72 hours from birth. Acceptable hemodynamic status is defined as the achievement and maintenance of dose success during the first 72 h from birth. The loss of such acceptable haemodynamic status occurs whenever there is a change in therapeutic strategy that involves cardiovascular treatment other than dobutamine alone due to exceeded safety parameters, treatment failure of the investigational infusion or the need for rescue treatment or death; any additional fluid bolus is considered as cardiovascular treatment.	72 hours
Absolute and relative frequencies of adverse events and severe adverse events	Absolute and relative frequencies of adverse events (AEs) and severe adverse events (SAEs), to be recorded and compared between groups. AEs are defined as any untoward medical occurrence in a patient or clinical investigation patients administered a medicinal product, which does not necessarily have a causal relationship with this treatment (the study medication). SAEs are defined as any untoward medical occurrence that at any dose: Results in death,; Is life-threatening; Requires inpatient hospitalization or prolongation of existing hospitalization; Results in persistent or significant disability/incapacity, or; Is a congenital anomaly/birth defect.; Other important medical events.	Through study completion, an average of 12 months

Collaborators and Investigators

• Sponsor: Instituto de Investigación Hospital Universitario La Paz

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2024
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: December 2, 2024
• First Submitted That Met QC Criteria: March 10, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 10, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Low superior vena cava flow; Hemodynamic insuffiency
• Additional Relevant MeSH Terms: Infant, Newborn, Diseases; Infant, Premature, Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Protective Agents; Adrenergic Agonists; Adrenergic Agents; Cardiotonic Agents; Adrenergic beta-Agonists; Sympathomimetics; Adrenergic beta-1 Receptor Agonists; Dobutamine
• Other Study ID Numbers: HULP 6422

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No