CIRCA DIEM Trial Information

Background

Circadian rhythms are vital to normal fetal development but the fetus is dependent on maternal circadian rhythms until near-term. Preterm infants spend the first months of postnatal life in the disruptive setting of constant environmental light and noise, without maternal circadian inputs. In animals, disturbed circadian rhythms are associated with impaired brain development. Cognitive impairment remains the primary morbidity associated with extremely preterm birth, and increases health care costs.

Objective

We aim to establish if individual diurnal cycling of environmental light and noise levels improves cognitive outcomes of very preterm infants compared to more constant background lighting and noise.

Study Design

A multicentre, prospective, randomised, open, blinded end-point (PROBE) parallel controlled trial that assesses the effect of non-invasive application of eye masks and ear muffs for 10 hours per night via measurements of neurodevelopmental, social, psychological, physiological, and economic outcomes.

Study Population

Babies born at < 31 weeks and 6 days postmenstrual age by best obstetric estimate (inborn or outborn) who will have initial care at a perinatal centre where routine care does not include individual environmental light/noise cycling. Written informed parental consent to trial participation will be obtained prior to or after birth.

Intervention

Participants allocated to the intervention group will receive individual environmental modification from birth until discharge home.

The environmental modification will cycle environmental light and noise exposure to ensure the infants are exposed to both "day" and "night" during their inpatient stay. Infants assigned to the intervention group will be exposed to a minimum of 300 lux and a maximum of 600 lux during the day and will not have protection from noise unless receiving high-frequency oscillatory ventilation. During the evening, the intervention group will wear black-out eye masks and ear muffs placed over silicone ear plugs. The day cycle (300-600 lux and no noise protection) will extend from 6 am to 8 pm (14 hours). The nocturnal cycle (eye masks and ear muffs/plugs) will be applied from 8 pm to 6 am (10 hours). Standardised eye masks, silicone plugs and ear muffs will be supplied, and applied during each period by the nurse caring for the infant.

Outcome Measures

Primary outcome:

Mean difference in cognitive score on Bayley Scales of Infant Development (BSID)- III at 2 years corrected age.

Secondary outcomes include:

Short term secondary outcomes will include enteral intake over the first 28 d, growth velocity (assessed weekly in hospital and every 2 months for the first 6 months post-discharge), neonatal morbidities (BPD/NEC/ROP/Sepsis/IVH), and length of hospital stay. Longer-term secondary outcomes will include survival, Bayley III sub-scores, percentages of the cohort with cognitive scores > 1 SD or 2 SD's below the mean; infant behaviour (ITSEA), growth, and health service utilisation. Health economics assessments will consider economic costs of length of stay, infant morbidity, health service utilisation, and neurodevelopmental outcome.

Data/Power Analysis

Sample size: to achieve 90% power and alpha 0.05 is calculated at 954 infants, assuming a standard deviation of 15 points, a 10% loss to follow-up and a 30% adjustment for multiple births.

Commencement Date

June 2018

Investigators and Primary Contacts

Chief Investigator: Jane Pillow, The University of Western Australia, jane.pillow@uwa.edu.au

Australia New Zealand Clinical Trials Registry

(ANZCTR) Trial Registry Number: ACTRN12618000371291p

Funding

Telethon Perth Children's Hospital Research Fund