Inflammation, Prematurity; Extreme
Conditions
Keywords
anakinra, IL-1Ra, bronchopulmonary dysplasia, diffuse white matter injury
Brief summary
Phase I/II study of anakinra to prevent the impact of perinatal inflammation in extremely premature infants.
Detailed description
With improvements in antenatal and neonatal care over the last 20 years, now infants are born as early as 22 weeks gestation and survive to discharge from hospital. This increased survival comes with increased risk of long term issues such as cerebral palsy and chronic lung disease. There is strong evidence to show these risks are increased due to an underlying inflammatory process initiated around the time of premature birth. This study aims to prove the safety of treating infants born between 24-27+6 weeks gestation with Anakinra, a medication which is similar to an anti-inflammatory molecule the body makes itself called Interleukin 1 Receptor Antagonist (IL-1Ra). Anakinra acts to reduce the inflammatory response and is currently used in adults and children as young as 8 months to manage autoimmune inflammatory conditions. This study looks at the safety of giving Anakinra to babies born extremely premature, over the first 3 weeks of life. Once safety is established, the investigators will conduct a larger trial studying the efficacy of this treatment for reducing the risk of long-term complications caused by neonatal inflammation in extremely preterm infants.
Interventions
DRUGAnakinra
Anakinra will be given to enrolled infants starting in the first 24hrs of life for the first 3 weeks of life.
Sponsors
Monash University
Hudson Institute of Medical Research
Te Whatu Ora - Health New Zealand
University of Auckland, New Zealand
Monash Medical Centre
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose escalation
Eligibility
Sex/Gender
ALL
Age
24 Weeks to 28 Weeks
Healthy volunteers
No
Inclusion criteria
* Born at 24 to 27+6 weeks gestation
Exclusion criteria
* Inability of the legal representatives to consent * Any disease or condition that the investigators judge could confound the trial results; these include, but are not limited to, genetic syndromes, severe cardiac abnormalities, substantial pre-/perinatal compromise (profound/severe hypoxia (SaO2 \<80% for \>3h), congenital diaphragmatic hernia, intrauterine stroke and others. * Imminent death
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment-related serious adverse reactions (suspected and unexpected) | 3 weeks | Monitoring of vital signs and documentation of any significant adverse effects, for the duration of treatment which is 3 weeks, such as cardiorespiratory deterioration requiring escalation of therapy (need to start or increase inotropic medication), need for cardiopulmonary resuscitation, incidence of sepsis and death within 15mins of infusion. Continuously collected physiological data will be summarised as area under the curve in 24h epochs. Serum creatinine will be monitored for incidence of acute kidney injury on days 3, 7 and 14. Liver function will be monitored for incidence of drug-induced liver injury on days 3, 7 and 14. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma interleukin-1 receptor antagonist levels will be measured and reported in pg/mL for each participant conferred by treatment with anakinra | 22 days | Blood will be taken prior to commencement of the trial medication, then at 6 & 12hr post-dose on days 1 and 22 and 12hr post dose on day 3, 7 and 14 and the IL-1Ra level recorded in pg/mL. |
Countries
Australia, New Zealand
Outcome results
None listed