With this study we aim to provide insight in the role of pulmonary RAS in the pathogenesis of ARDS in neonates and children. This study is performed in the context of a comparative study assessing the impact of age on the pulmonary RAS in ARDS. We…
ID
Source
Brief title
Condition
- Ancillary infectious topics
- Lower respiratory tract disorders (excl obstruction and infection)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameters are the different RAS components measured in
bronchoalveolare lavage fluid (BALF) and blood at different time points.
Secondary outcome
- Effector molecules of the pulmonary RAS (including cytokines, compoments of
coagulation and fibrotic components)
- Oxygenation index (OI); alveolar-arterial oxygen difference (DD(A-a)O2);
PaO2/FIO2 ratio
- Score for Neonatal Acute Physiology II (SNAPII) or pediatric risk of
mortality score (PRISM).
- Ventilator-free days (VFDs)
- Bronchopulmonary dysplasia (BPD)
- Mortality: within 60 days after study enrolment
Background summary
Children have a lower incidence and mortality from acute respiratory distress
syndrome (ARDS) than adults. In addition, experimental models of ARDS show that
adult animals are more susceptible to lung injury than newborn or young
animals. The age dependent mechanisms by which injury responses in the lungs
are acquired are unknown. Age dependent changes in the pulmonary
renin-angiotensin system (RAS) might offer an explanation for the differences
in susceptibility to and outcome of ARDS between children and adults. The two
key enzymes of the RAS, Angiotensin Converting Enzyme (ACE) and ACE2, have
opposite actions. ACE functions as a lung injury-promoting factor via
production of its effector peptide Angiotensin (Ang) II. In contrast, ACE2
functions as a lung protective factor by degradation of Ang II and generating
Ang-(1-7). Recently, an imbalance between ACE and ACE2 was shown in
experimental ARDS models. Moreover, experimental data indicate that aging is
associated with increased ACE and decreased ACE2 production in several tissues,
including the lung.
Study objective
With this study we aim to provide insight in the role of pulmonary RAS in the
pathogenesis of ARDS in neonates and children. This study is performed in the
context of a comparative study assessing the impact of age on the pulmonary RAS
in ARDS. We hypothesize that neonates and children have a relatively more
active pulmonary ACE2 pathway at the expense of the ACE pathway compared to
elderly patients, which affects the susceptibility and course of ARDS.
Study design
An investigator-initiated observational study at the neonatal intensive care
unit (NICU) or pediatric intensive care unit (PICU). Mechanically ventilated
neonates and children at risk for ARDS are subjected to serial bronchoalveolar
lavages (BAL) (as previous described in the research protocol (METC 98/099 and
METC 06/165), approved by the METC of the AMC) and blood collection, aiming to
determine the levels of the different RAS components. An identical study
protocols will be applied at the adult intensive care unit in order to
determine whether there are differences between the different age groups.
Study burden and risks
The BAL procedure has found to be a safe procedure in neonates and children. It
is previously used in the research protocol (METC 98/099 or METC 06/165),
approved by the METC of the AMC after a pilot was performed assessing the
potential complications of this procedure. Blood sample volumes will be limited
to 1 ml and collection will be performed within the daily routine collections
using an indwelling arterial catheter. Therefore the risks and burden
associated with this study protocol can be considered as minimal.
Patients included in the study do not have a direct benefit from the study. The
purpose of this study is to investigate the role of pulmonary RAS during ARDS
at all ages. We aim to identify biological distinctions in RAS response during
ARDS between different age groups, which may influence the course and outcome
of the disease. Insight into the role of maturation and aging in the context of
ARDS can lead to novel targets for age directed therapeutic options.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
•Signed informed consent by the parents or legal caretakers.
•Admitted to the neonatal intensive care unit (NICU) or pediatric intensive care unit (PICU) of the Emma Children*s Hospital, Academic Medical Center of Amsterdam, the Netherlands.
•Intubated and mechanically ventilated, with an anticipated duration of mechanical ventilation of at least 48 hours at enrolment (as judged by the investigator or the neonatologist on duty).
•Enrolment within 24 hours after the start of mechanical ventilation.
•Body weight of 1 kg or more at the time of enrolment.
•Two or more of the following criteria at the time of enrolment:
o Hypothermia (< 36 °C), fever (> 38.0 °C), or body temperature instability.
o Bradycardia or tachycardia, according to age, or a prolonged capillary refill time.
o Leukopenia or leucocytosis, according to age, or more than 10 % banded neutrophils.
o Tachypneu or apneu*s, according to age, or cyanosis
Exclusion criteria
•Neonates with a postconceptual age less than 32 weeks within 1 week post partum.
•Immune compromised; chronic respiratory failure, neuromuscular diseases, cyanotic congenital heart disease or signs of cardiogenic pulmonary edema, severe congenital pulmonary abnormalities.
•(Previous) use of medication which intervene with the RAS
•Previous mechanical ventilation, surfactant or NO-therapy within 1 week before eligibility for enrolment into the study.
•Longer than 48 hours antibiotics previous to IC-admission.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL42386.018.12 |