Haemodynamic insufficiency (Haemodynamic insufficiency after birth is commonly seen in babies born prematurely. The condition has a significant clinical impact. A final common pathway is seen but the consequences of functional impairment are diverse. During the neonatal period haemodynamic insufficiency can lead to loss of existing function and the loss of function that is yet to be developed.) MedDRA version: 20.0 Level: PT Classification code 10009196 Term: Circulatory failure neonatal Syste
Conditions
Interventions
Product Name: Dobutamine
Product Code: Dobutamine Hydrochloride
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: DOBUTAMINE HYDROCHLORIDE
CAS Number: 49745-95-1
Concentration unit: mg/m
Sponsors
SERMAS-FIBHULP
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Infants are eligible to be included in the study only if they meet all of the following criteria: • 24(+0) to 32(+6) weeks gestation • Admitted in the neonatal intensive care unit • Presence of haemodynamic insufficiency, defined as the presence of one or more of the following within first 72 hours after birth: o MABP 4 mm/l OR o SVC flow =65 years) no F.1.3.1
Exclusion criteria
Exclusion criteria: Patients will be excluded from the study if they meet any of the following 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 commercial dobutamine treatment • Infants with congenital malformations likely to affect cardiovascular adaptation (including: congenital diaphragmatic hernia, gastroschisis or congenital heart defects). • Infants in whom a surgical treatment is planned within 72 hours of birth • Infants carrying chromosomal anomalies • Lack of parental signed informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To demonstrate (short-term objective) that fluid bolus and dobutamine infusion as compared to fluid bolus and placebo infusion increases the proportion of neonates achieving and maintaining a clinically acceptable haemodynamic status with the dobutamine investigational infusion alone in the first 72 hours from birth. • To demonstrate (medium-term objective) that fluid bolus and dobutamine infusion as compared to fluid bolus and placebo infusion increases the proportion of neonates alive without severe neurological complications at term-equivalence.;Secondary Objective: • To assess (long term objective) the efficacy of dobutamine on long-term neurodevelopmental outcome. • To evaluate (safety objective) the safety of dobutamine for the whole study population as well as for the three treatment groups separately. • To assess which starting dose of dobutamine (2.5 µg/kg/min vs. 5 µg/kg/min) leads to better short-term outcomes. • To assess the concentration/effect relationship of dobutamine and determine the individual covariates explaining the inter-individual pharmacokinetic/pharmacodynamics variability. • To evaluate the effect of dobutamine therapy on infants with different genetic background for high vs. low genetic blood pressure estimates.;Timepoint(s) of evaluation of this end point: (1) Short term: The first 72 hours from birth (2) Medium term: Term equivalent age (TEA);Primary end point(s): Two co-primary efficacy endpoints will be investigated: (1) Short term (pharmacodynamic) endpoint: proportion of neonates achieving and maintaining a clinically acceptable haemodynamic status [A] with the dobutamine investigational infusion alone in the first 72 hours from birth. (2) Medium term (clinical) endpoint: Proportion of neonates surviving without severe neurological complications [B] at term equivalent age (TEA) [C]. [A] Acceptable haemodynamic status with investigational infusion is defined, for the purposes of this study, as the achievement an | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Proportion of patients that arrive at 24 months corrected gestational age without neurodevelopmental disability. • Absolute and relative frequencies of AEs and SAEs, to be recorded and compared between groups. -Optimal Starting Dose: Defined as the starting dose that provides the minimum number of dose steps until the efficient dose. - Population pharmacokinetics and PK/PD modelling based on sparse blood sampling yielding the following endpoints: Lack of bias of the model on the Visual Predictive Checks and Goodness of fit plots, Residual standard Errors > 50 % on the estimated PK/PD parameters. -Response of infants to dobutamine therapy with high (> percentile 75), intermediate (percentile 25-75) and low (< percentile 25) genetic blood pressure estimates.;Timepoint(s) of evaluation of this end point: Long term objective: 24 months | — |
Countries
Spain, Turkey
Contacts
Public ContactMarta Pavía
Mrs
Outcome results
None listed