Poppi - Procedural pain in premature infants
A single centre randomised placebo-controlled trial investigating the efficacy of morphine analgesia for procedural pain in infants. This trial is led by Dr Eleri Adams and Dr Rebeccah Slater in collaboration with the NPEU and the Paediatric and Infant Pain & Anaesthesia (PiPA) group.
The aim of the Poppi Trial (Procedural Pain in Premature Infants) is to test whether morphine can provide effective pain relief in babies during invasive medical procedures. While morphine is frequently given to adults when they experience pain, it is not clear whether morphine provides effective pain relief in babies. This means morphine is usually not prescribed to babies when clinical staff perform clinically-essential medical procedures.
An example of a painful procedure that is frequently and regularly performed on premature babies is an eye exam that tests for Retinopathy of Prematurity – this is a disease which if untreated can lead to permanent blindness. Although the eye exam is considered to be painful, and stressful for both infants and parents, and can result in unstable breathing and heartbeat for up to 24 hours after the exam, the pain relief currently provided during this procedure, which includes sucrose, breast milk and topical eye drops, has been shown to be ineffective.
The Poppi trial will use clinical pain assessment tools to measure pain in babies during the eye exam and during a clinically-required blood test. We will test whether babies who are given morphine experience less pain, and whether this improves the stability of the babies breathing and heartbeat after the procedure. We will also use some recently developed brain-imaging techniques to observe how morphine can affect pain-related brain activity. Given that babies cannot tell us when they are in pain, this is an important new approach which will help us understand how the infant brain processes pain and will tell us whether pain-relieving drugs are effectively reducing patterns of pain-related brain activity.
- EudraCT No.:
- REC Reference:
- Clinical Trials Unit:
- National Perinatal Epidemiology Unit CTU
- University of Oxford
- The Wellcome Trust and NIHR Efficacy and Mechanism Evaluation (EME) Programme
- Recruitment Target:
- 156 babies (33 month recruitment period)
- Duration of Study:
- September 2015 - November 2018
Babies on the neonatal unit at the John Radcliffe Hospital, Oxford will be considered for inclusion into the trial if:
- They are born less than 32 weeks’ gestation or birth weight <1501 g
- They are between 34 and 42 weeks gestational age at the time of the study
- They require a clinical heel lance and retinopathy of prematurity (ROP) screening on the same test occasion.
- The parents/guardians have consented to inclusion in the trial.
Babies will be excluded from participation in the trial if they:
- Have intraventricular haemorrhage > grade II
- Have short bowel syndrome
- Are receiving nil by mouth due to documented gut pathology
- Received opiates in the last 72 hours
- Received other analgesics or sedatives in the last 24 hours
- Have a previously documented episode of morphine sensitivity
- Have a congenital malformation or genetic condition known to affect neurological development
- Are born to mothers who regularly use opiates during pregnancy or while breastfeeding or expressing breast milk.
Or senior clinician considers inclusion in trial to be medically inappropriate.
Babies will be randomly allocated to receive either morphine sulphate or placebo (inactive solution) prior to ROP screening. Neither parents nor staff caring for a baby will know which treatment has been allocated- a blinded randomised controlled trial.
During the ROP screening and after the drug has been administered, the babies will be attached to the EEG, EMG and video monitoring equipment. A clinical heel lance and heel lance-control stimuli (where the lancet is rotated such that on release the blade does not touch the foot) will be performed. During each procedure pain-related (nociceptive-specific) brain activity will be recorded.
To test whether administration of morphine reduces clinical pain scores (Premature infant pain profile -PIPP) during the 30 second period after ROP screening compared with a placebo (inactive solution).
To test whether administration of morphine reduces nociceptive-specific brain activity following a clinically-essential heel lance compared with a placebo (inactive solution).
To test whether administration of morphine improves clinical stability after ROP screening in the 6-hour and 24-hour period following the exam.
To test whether administration of morphine reduces clinical pain scores (PIPP) and reflex withdrawal activity following a clinically-essential heel lance compared with a placebo (inactive solution).
To test whether administration of morphine is safe by determining whether it results in episodes of respiratory depression or hypotension that require intervention compared with a placebo.