title: A blinded randomised placebo-controlled trial investigating the efficacy of morphine analgesia for procedural pain in infants: Trial protocol.
abstract: Infant pain has both immediate and long-term negative consequences, yet in clinical practice it is often undertreated. To date, few pain-relieving drugs have been tested in infants. Morphine is a potent analgesic that provides effective pain relief in adults, but there is inconclusive evidence for its effectiveness in infants. The purpose of this study is to establish whether oral morphine provides effective analgesia for procedural pain in infants. A blinded, placebo-controlled, parallel-group randomized, phase II, clinical trial will be undertaken to determine whether morphine sulphate administered orally prior to clinically-required retinopathy of prematurity (ROP) screening and heel lancing provides effective analgesia.  156 infants between 34 and 42 weeks' gestational age who require a clinical heel lance and ROP screening on the same test occasion will be included in the trial. Infants will be randomised to receive either a single dose of morphine sulphate (100 μg/kg) or placebo. Each infant will be monitored for 48 hours and safety data will be collected during the 24 hours following drug administration. The primary outcome will be the Premature Infant Pain Profile-revised (PIPP-R) score 30 seconds after ROP screening. The co-primary outcome will be the magnitude of nociceptive-specific brain activity evoked by a clinically-required heel lance. Infant clinical stability will be assessed by comparing the number of episodes of bradycardia, tachycardia, desaturation and apnoea, and changes in respiratory support requirements in the 24-hour periods before and after the clinical intervention. In addition, drug safety will be assessed by considering the occurrence of apnoeic and hypotensive episodes requiring intervention in the 24-hour period following drug administration. This study has been published as anAccepted Protocol SummarybyThe Lancet.
authors.affiliation: Department of Paediatrics, University of Oxford, Oxford, UK.
authors.forename: Rebeccah
authors.identifier: 0000-0003-1595-4846
authors.initials: R
authors.lastname: Slater
authors.affiliation: Department of Paediatrics, University of Oxford, Oxford, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Hartley
authors.affiliation: Department of Paediatrics, University of Oxford, Oxford, UK.
authors.forename: Fiona
authors.initials: F
authors.lastname: Moultrie
authors.affiliation: Department of Paediatrics, University of Oxford, Oxford, UK.
authors.forename: Eleri
authors.initials: E
authors.lastname: Adams
authors.affiliation: National Perinatal Epidemiology Unit (NPEU), University of Oxford, Oxford, UK.
authors.forename: Ed
authors.initials: E
authors.lastname: Juszczak
authors.affiliation: Nuffield Department of Anaesthetics, John Radcliffe Hospital, Oxford, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Rogers
authors.affiliation: MRC Centre for Reproductive Health, The Queen's Medical Research Institute, Edinburgh, UK.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Norman
authors.affiliation: Oxford Eye Hospital, John Radcliffe Hospital, Oxford, UK.
authors.forename: Chetan
authors.initials: C
authors.lastname: Patel
authors.affiliation: National Perinatal Epidemiology Unit (NPEU), University of Oxford, Oxford, UK.
authors.forename: Kayleigh
authors.initials: K
authors.lastname: Stanbury
authors.affiliation: Department of Paediatrics, University of Oxford, Oxford, UK.
authors.forename: Amy
authors.initials: A
authors.lastname: Hoskin
authors.affiliation: Department of Paediatrics, University of Oxford, Oxford, UK.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Green
keywords: Analgesia; Brain; EEG; Infant; Morphine; Pain; Retinopathy of Prematurity