Abstract:
<h4>Introduction</h4>Infants with severe or recurrent transitional hypoglycaemia continue to have high rates of adverse neurological outcomes and new treatment approaches are needed that target the underlying pathophysiology. Diazoxide is one such treatment that acts on the pancreatic β-cell in a dose-dependent manner to decrease insulin secretion.<h4>Methods and analysis</h4>Phase IIB, double-blind, two-arm, parallel, randomised trial of diazoxide versus placebo in neonates ≥35 weeks' gestation for treatment of severe (blood glucose concentration (BGC)<1.2 mmol/L or BGC 1.2 to <2.0 mmol/L despite two doses of buccal dextrose gel and feeding in a single episode) or recurrent (≥3 episodes <2.6 mmol/L in 48 hours) transitional hypoglycaemia. Infants are loaded with diazoxide 5 mg/kg orally and then commenced on a maintenance dose of 1.5 mg/kg every 12 hours, or an equal volume of placebo. The intervention is titrated from the third maintenance dose by protocol to target BGC in the range of 2.6-5.4 mmol/L. The primary outcome is time to resolution of hypoglycaemia, defined as the first point at which the following criteria are met concurrently for ≥24 hours: no intravenous fluids, enteral bolus feeding and normoglycaemia. Groups will be compared for the primary outcome using Cox's proportional hazard regression analysis, expressed as adjusted HR with a 95% CI.<h4>Ethics and dissemination</h4>This trial has been approved by the Health and Disability Ethics Committees of New Zealand (19CEN189). Findings will be disseminated in peer-reviewed journals, to clinicians and researchers at local and international conferences and to the public.<h4>Trial registration number</h4>ACTRN12620000129987.
