Dobutamine in the Treatment of Haemodynamic Insufficiency in the Immediate Postnatal Period

Summary

Haemodynamic insufficiency after birth is seen commonly in babies born prematurely and is associated with adverse outcomes. In current clinical practice, a combination of blood pressure and clinical signs is used to guide therapy. However, blood pressure is a poor surrogate of systemic and organ (brain) blood flow distribution during transitional circulation. This state is characterised by increased peripheral vascular resistance and increased afterload causing myocardial depression and impaired blood flow distribution in spite of 'normal' blood pressure. Echocardiography-Doppler (Echo-D) measurement of superior vena cava (SVC) flow has been proposed as a more clinically relevant marker of circulatory impairment shortly after birth than systemic hypotension. When there is low SVC flow, several small-scale clinical trials have suggested dobutamine as the optimal therapeutic option. However the associations between SVC flow and short- and long- term outcomes are not strong enough to allow SVC flow alone to be the basis for the inclusion of patients into a confirmatory trial to demonstrate the efficacy and safety of dobutamine.

NeoCirc-001 - The primary objective is to answer some important questions required for the design of a subsequent placebo-controlled trial (NeoCirc-003), which will evaluate the effectiveness of a new neonatal formulation of dobutamine to treat haemodynamic insufficiency in the first 72 hours after birth in babies born at less than 33 weeks' gestation. Observational data will be collected from this population with a view to determining the degree to which diagnostic measures influence treatment decisions. The primary outcome is death or worst cranial ultrasound (CUS) appearance at or before 36 weeks' gestation.

NeoCirc-001A - The primary objective is to estimate the elimination half-life, and consequently the time to steady-state of dobutamine in extremely premature neonates.

NeoCirc-001B - The primary objective is to construct a population pharmacokinetic pharmacodynamic model that will be validated using samples collected during the confirmatory trial (NeoCirc-003).

Conditions

• Shock

Interventions

DRUG

Dobutamine

Infants who meet the definition of poor perfusion state will be treated at the discretion of the responsible physician following the standard local policies. The interventions will be dobutamine from a new neonatal formulation developed for NeoCirc and/or other treatments (including any other cardiovascular drug or volume replacement with normal saline).

Sponsors & Collaborators

• Hospital Universitario La Paz

  collaborator OTHER

• Brighton and Sussex University Hospitals NHS Trust

  collaborator OTHER

• University of Luebeck

  collaborator OTHER

• Servicio Vasco de Salud Osakidetza, Spain

  collaborator UNKNOWN

• University of Liverpool

  collaborator OTHER

• Vest Children´s Hospital, Germany

  collaborator UNKNOWN

• Datteln University Witten-Herdecke

  collaborator UNKNOWN

• Iuliu Hatieganu University of Medicine and Pharmacy

  collaborator OTHER

• Semmelweis University

  collaborator OTHER

• University of Pecs

  collaborator OTHER

• Gazi University

  collaborator OTHER

• Tufts Medical Center

  collaborator OTHER

• Hannover Medical School

  collaborator OTHER

• Onorach Clinical Dundee, Scotland

  collaborator UNKNOWN

• Proveca Limited Daresbury, England

  collaborator UNKNOWN

• Institut National de la Santé Et de la Recherche Médicale, France

  collaborator OTHER_GOV

• Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz

  lead OTHER

Principal Investigators

• Adelina Pellicer, MD PhD · SERMAS La Paz University Hospital

• Heike Rabe, MD PhD · Brighton and Sussex University Hospitals (BSUH)

• Fernando Cabañas, MD PhD · Servicio Madrileño de Salud (SERMAS)

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Max Age

72 Hours

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-05-30

Primary Completion

2015-10-13

Completion

2017-10-10

Countries

• Spain

Study Locations