Provisions for post-trial care {30}
TOLERANCE, RECURRENCE
Similar to clinical practice, the clinical team should monitor participants who have weaned off study drug for 48–72 h prior to discharge to ensure that recurrence of NOWS signs do not occur. If there is a recurrence of NOWS signs during the 48–72 h post-intervention period, and if that recurrence merits pharmacologic therapy per the institution’s guideline, study drug will be restarted at the prior dose of the rapid wean (25% of stabilization dose) or the slow wean (20% of the stabilization dose) interventions. Tolerance for weaning will then be re-evaluated after 24 h of study drug administration. When the infant has been off the opioid and prior to discharge, a trained examiner will administer the NNNS. The assessment takes approximately 20–25 min to complete. We will not administer the NNNS at the same time relative to the last opioid exposure due to the unpredictable number and timing of opioid escalations in each weaning intervention and to avoid potential unblinding of the intervention.