Bicarbonate for AcidosiS in very pretErm babies: a randomised clinical trial: The BASE Trial

Background: Sodium bicarbonate (SB) is widely, but not universally, used to treat metabolic acidosis (MA) in very preterm (VPT) babies but the evidence underpinning its use is poor. SB is believed to correct MA and so improve cardiac function. However, the use of SB can lead to worsening of intracellular acidosis with consequent adverse outcomes.

Aims and Objectives: The aim of this study is to evaluate the safety, clinical and cost-effectiveness of the routine use of SB to treat MA in VPT babies compared to not using SB. The primary objective is to evaluate the effect of SB on survival to discharge from neonatal care without major morbidity. The secondary objectives are to evaluate the impact of SB on survival without moderate to severe neurodevelopmental impairment at 2-years of age corrected for prematurity, individual major morbidities during neonatal care, duration of neonatal unit stay and cost effectiveness.

Research question: In VPT babies born <31 weeks’ gestation with MA (P), does a pathway of routine use of SB (I) compared to no routine treatment with SB (C) increase or decrease the risk of survival to discharge from neonatal care without major morbidity (O)?

Design: Multicentre, pragmatic, open-label, two-arm, parallel-group, opt-out, randomised controlled trial, with an internal pilot and integrated health economic analysis. Setting: NHS neonatal units in the UK

Methods: Enrolled babies will be randomised when they meet the inclusion criteria of MA to a care pathway of either routine use of SB for MA or no treatment with SB. All other aspects of care, including treatment for MA occurring during or after cardiopulmonary resuscitation, will be determined by the treating clinician, in keeping with the practice of the neonatal unit.

Outcomes: Primary: survival to discharge from neonatal care without major morbidity. Major morbidities comprise: 1) bronchopulmonary dysplasia, 2) treatment for retinopathy of prematurity, 3) major brain injury (grade 3 / 4 IVH or periventricular leukomalacia (PVL)), 4) late-onset sepsis, 5) severe necrotising enterocolitis and 6) need for major surgery.

Key secondary: Survival without moderate to severe neurodevelopmental impairment at 2-years of age corrected for prematurity.

Other secondary: Individual major morbidities during neonatal care, duration of neonatal unit stay and cost effectiveness.

Sample size: A total of 3,764 babies (1,882 in each group) would have 90% power (2-sided 5% significance) to detect an absolute risk difference (increase or decrease) of 6% in the primary outcome rate (from 53% to 47%, or 53% to 59%) allowing for inflation by 1.29 to allow for 10% cross over from control to intervention and 2% from intervention to control.

Timelines: i) regulatory approvals and set-up, 6 months ii) recruitment including internal pilot 36 months iii) follow up to discharge 3 months iv) 2-year outcomes 27 months v) database lock, analysis and final report 6 months. Total duration 75 months.

Impact: This study will be the first adequately powered trial to study the safety and efficacy, both in the short and long-term, of the use of SA to treat MA in VPT babies. Regardless of the study’s result, the BASE trial will lead to more evidence-based practice and cost-effective care of VPT worldwide.

Dissemination: Results of the study will be publicised via a study website, study social media accounts, conferences, publications, presentations and targeted messages to all stakeholders.