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

NCT ID: NCT03311178

Last Updated: 2017-10-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-05-30

Study Completion Date

2017-10-10

Brief Summary

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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).

Detailed Description

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Conditions

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Shock

Keywords

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Shock Preterm infant Dobutamine

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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).

Group Type EXPERIMENTAL

Dobutamine

Intervention Type DRUG

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).

Interventions

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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).

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Target population for informed consent:

* neonates 24 to 32+6 weeks´ gestation,
* postnatal age \<72 hours;

Infants eligible for circulatory failure pathway:

* parental informed consent obtained;
* The infants will be assessed, as per routine clinical practice, for clinical signs indicating infants at risk of poor perfusion, and will be recruited if they develop haemodynamic insufficiency defined as: either two or more of: (i) Mean blood pressure (MBP) \< gestational age (GA)-1 mmHg (invasive/non-invasive, two readings 15 min apart); (ii) SVC flow \< 51 ml/kg/min; (iii) capillary refill time (CRT) \> 4 sec; (iv) Lactate \> 4 mmol/l (v) Base excess \<-9 mmol/l or: MBP \< GA -5 mmHg (invasive/non-invasive, two readings 15 min apart)

Exclusion Criteria

* non-viability;
* congenital hydrops or malformations likely to affect cardiovascular adaptation;
* surgery planned within 72 hours of birth;
* chromosomal anomalies;
* informed consent form (ICF) not signed.
Maximum Eligible Age

72 Hours

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospital Universitario La Paz

OTHER

Sponsor Role collaborator

Brighton and Sussex University Hospitals NHS Trust

OTHER

Sponsor Role collaborator

University of Luebeck

OTHER

Sponsor Role collaborator

Servicio Vasco de Salud Osakidetza, Spain

UNKNOWN

Sponsor Role collaborator

University of Liverpool

OTHER

Sponsor Role collaborator

Vest Children´s Hospital, Germany

UNKNOWN

Sponsor Role collaborator

Datteln University Witten-Herdecke

UNKNOWN

Sponsor Role collaborator

Iuliu Hatieganu University of Medicine and Pharmacy

OTHER

Sponsor Role collaborator

Semmelweis University

OTHER

Sponsor Role collaborator

University of Pecs

OTHER

Sponsor Role collaborator

Gazi University

OTHER

Sponsor Role collaborator

Tufts Medical Center

OTHER

Sponsor Role collaborator

Hannover Medical School

OTHER

Sponsor Role collaborator

Onorach Clinical Dundee, Scotland

UNKNOWN

Sponsor Role collaborator

Proveca Limited Daresbury, England

UNKNOWN

Sponsor Role collaborator

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

OTHER_GOV

Sponsor Role collaborator

Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz

OTHER

Sponsor Role lead

Responsible Party

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Adelina Pellicer

Chief Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Adelina Pellicer, MD PhD

Role: STUDY_CHAIR

SERMAS La Paz University Hospital

Heike Rabe, MD PhD

Role: STUDY_DIRECTOR

Brighton and Sussex University Hospitals (BSUH)

Fernando Cabañas, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Servicio Madrileño de Salud (SERMAS)

Locations

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La Paz University Hospital, Department of Neonatology

Madrid, , Spain

Site Status

Countries

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Spain

References

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Kluckow M, Evans N. Low superior vena cava flow and intraventricular haemorrhage in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2000 May;82(3):F188-94. doi: 10.1136/fn.82.3.f188.

Reference Type BACKGROUND
PMID: 10794784 (View on PubMed)

Kluckow M, Evans N. Superior vena cava flow in newborn infants: a novel marker of systemic blood flow. Arch Dis Child Fetal Neonatal Ed. 2000 May;82(3):F182-7. doi: 10.1136/fn.82.3.f182.

Reference Type BACKGROUND
PMID: 10794783 (View on PubMed)

Osborn DA, Paradisis M, Evans N. The effect of inotropes on morbidity and mortality in preterm infants with low systemic or organ blood flow. Cochrane Database Syst Rev. 2007 Jan 24;2007(1):CD005090. doi: 10.1002/14651858.CD005090.pub2.

Reference Type BACKGROUND
PMID: 17253539 (View on PubMed)

Dempsey EM, Barrington KJ. Treating hypotension in the preterm infant: when and with what: a critical and systematic review. J Perinatol. 2007 Aug;27(8):469-78. doi: 10.1038/sj.jp.7211774.

Reference Type BACKGROUND
PMID: 17653217 (View on PubMed)

Other Identifiers

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Neocirculation 001

Identifier Type: -

Identifier Source: org_study_id