Clinical trial NCT01438008: Pilot Study of Sucrose to Reduce Pain in Sick Babies
Official title: Be Sweet to Sick Babies: Analgesic Effects of Oral Sucrose and Concomitant Opioid Analgesics; a Pilot Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Pain Due to Certain Specified Procedures
Keywords: Sucrose
Pain
Lead sponsor: Children's Hospital of Eastern Ontario
Sponsor class: OTHER
Collaborators: name: University of Ottawa
First posted: 2011-09-21
Enrollment: 9
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Small amounts of sweet tasting sugar water reduces pain in babies during painful blood tests and injections. The investigators do not know if sugar also reduces pain in babies already receiving a continuous infusion of opioid analgesics. This project will help determine if small amounts of sugar water reduce pain in babies already receiving a continuous infusion of opioid analgesic during a heel lance procedure or nasogastric/orogastric (NG/OG) tube insertions. The investigators hypothesize that infants who are receiving opioid analgesics will have lower pain scores during their blood tests (heel lance) or NG/OG tube insertion, when sucrose is given, compared to when water is given.

Detailed description: Background: Sick infants nursed in Neonatal Intensive Care Units (NICU) are exposed to large numbers of repeated painful procedures during their hospitalization \[1-6\]. Effectively reducing pain during these frequently performed and repeated painful procedures minimizes short term behavioural and physiological responses to pain, and has the potential to reduce long term adverse effects, including altered responses to subsequent pain \[7\] and increased risk of adverse neurodevelopmental, behavioural, and cognitive outcomes \[8\] The effectiveness of sucrose and other sweet solutions in the reduction of pain during painful procedures in infants has been well established. Despite the large numbers of randomized controlled trials (RCTs) of sweet solutions for procedural pain reduction in infants, there remain significant knowledge and research gaps. One of the key unanswered questions is whether sweet solutions reduce pain when given with concomitant opioid analgesics \[9\].

Rationale: Sick infants in hospital need to have blood tests as part of their medical care. Oral sucrose and glucose has shown to effectively reduce behavioural responses to pain and pain scores during commonly performed painful procedures in preterm and term newborn infants and infants up to 12 months of age. However, the investigators do not know if this also works for infants already receiving a continuous infusion of opioid analgesics. The aim is to establish preliminary evidence of the effectiveness of oral sucrose in reducing pain during heel lancing or NG/OG tube insertion when concomitant opioid analgesics are being administered, and to use the pilot data to inform a full scale RCT.

Hypothesis: Infants who are receiving opioid analgesics will have lower pain scores during their blood tests (heel lance) or NG/OG tube insertion, when sucrose is given, compared to when water is given.

Primary Objective: To obtain preliminary data about the effectiveness of sucrose and concomitant opioid analgesics compared to opioid analgesics alone during the painful procedure of heel lancing or NG/OG tube insertion to inform a full scale RCT.

Secondary Objectives: To determine the acceptability of the interventions to infants' parents and to use these results to help us calculate sample size for a subsequent full trial.

Methods: A single-center, randomized, double-blind, placebo controlled pilot trial will be conducted in an urban tertiary care pediatric university-affiliated hospital NICU. The study population is all infants who are inpatients in the Neonatal Intensive Care Unit (NICU) who are receiving a continuous infusion of opioid analgesics and who require a heel lance for the purpose of medically-required capillary blood sampling or a NG/OG tube insertion. Study participants will be randomly allocated to receive 24% sucrose solution or a placebo solution (water). The maximum amount of the study solution will be administered according to the infant's gestational age and according to the hospital's Sucrose policy:

\<28 weeks gestation = maximum dose of 0.1 mL; 28-31 weeks gestation = maximum dose of 0.3 mL; 32-35 weeks gestation = maximum dose of 0.5 mL; \>36 weeks gestation = maximum dose between 0.5-1.0 mL.

The primary outcome measure is the difference in pain levels during the heel lance procedure or NG/OG tube insertion in the study population as assessed by the Premature Infant Pain Profile (PIPP).

Secondary outcomes will include; i) total crying time; ii) skin conductance activity, a valid, non-invasive, physiological measure of pain and stress in infants.

Statistical analysis: PIPP scores, crying time, and skin conductance activity will be summarized using mean and standard deviation if normally distributed, and median and interquartile range (IQR) if non-normally distributed. An intention to treat analysis will be performed.

Eligibility criteria: Inclusion Criteria:

Infants who are inpatients of the NICU:

* Who are receiving a continuous intravenous infusion of an opioid analgesic such as morphine or fentanyl at a maximum dose equivalent to 20 mcg/kg/hr of morphine and;
* Who require heel lance for medically required blood sampling or nasogastric/orogastric (NG/OG) tube insertions and;
* Who are eligible to receive sucrose as per the hospital's Sucrose policy for infants.

Exclusion Criteria:

* Infants less than 25 weeks gestation
* Infants with any injury to the skin where the probe needs to be placed
* Infants with an implanted defibrillator or pacemaker
* Infants with an injury affecting sympathetic nerve conduction
* Infants exposed to antenatal methadone
* Infants who, aside from being on opioid analgesics, are ineligible to receive sucrose as per the hospital's Sucrose policy38
* If the infant's mother wishes to breastfeed during the procedure
* Infants with known or suspected fructose intolerance
* Infants with spinal cord malformation (e.g. myelomeningocele and sacral teratoma) since these infant's response, and sensitivity to pain may differ from infants without spinal cord malformations
* Infants who are unconscious, heavily sedated and those with absent gag and/or swallow reflex
* Infants who are in isolation with only essential personnel caring for them
* To ensure there is no interaction effect of muscle relaxants, which may impact on infants' ability to mount a behavioural response to pain, assessments will not be conducted until a period of 24 hours since the previous muscle relaxant dose
* Parental language barrier (if unable to speak/understand French and/or English)

Primary outcomes:
measure: Premature Infant Pain Profile (PIPP)
timeFrame: Baseline, day one of blood test
Secondary outcomes:
measure: Total Crying Time
timeFrame: Total crying time were recorded as a proportion of the time spent crying over the total length of procedure and/or in the 3 minutes that followed.
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
Study officials:
affiliation: Children's Hospital of Eastern Ontario
name: Denise Harrison, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Barker DP, Rutter N. Exposure to invasive procedures in neonatal intensive care unit admissions. Arch Dis Child Fetal Neonatal Ed. 1995 Jan;72(1):F47-8. doi: 10.1136/fn.72.1.f47.
citation: Carbajal R, Rousset A, Danan C, Coquery S, Nolent P, Ducrocq S, Saizou C, Lapillonne A, Granier M, Durand P, Lenclen R, Coursol A, Hubert P, de Saint Blanquat L, Boelle PY, Annequin D, Cimerman P, Anand KJ, Breart G. Epidemiology and treatment of painful procedures in neonates in intensive care units. JAMA. 2008 Jul 2;300(1):60-70. doi: 10.1001/jama.300.1.60.
citation: Harrison D, Loughnan P, Manias E, Johnston L. Analgesics administered during minor painful procedures in a cohort of hospitalized infants: a prospective clinical audit. J Pain. 2009 Jul;10(7):715-22. doi: 10.1016/j.jpain.2008.12.011. Epub 2009 Apr 23.
citation: Johnston CC, Collinge JM, Henderson SJ, Anand KJ. A cross-sectional survey of pain and pharmacological analgesia in Canadian neonatal intensive care units. Clin J Pain. 1997 Dec;13(4):308-12. doi: 10.1097/00002508-199712000-00008.
citation: Porter FL, Anand KJ. Epidemiology of Pain in Neonates. Research & Clinical Forums 20(4): 9-16, 1998.
citation: Simons SH, van Dijk M, Anand KS, Roofthooft D, van Lingen RA, Tibboel D. Do we still hurt newborn babies? A prospective study of procedural pain and analgesia in neonates. Arch Pediatr Adolesc Med. 2003 Nov;157(11):1058-64. doi: 10.1001/archpedi.157.11.1058.
citation: Taddio A, Katz J. The effects of early pain experience in neonates on pain responses in infancy and childhood. Paediatr Drugs. 2005;7(4):245-57. doi: 10.2165/00148581-200507040-00004.
citation: Grunau RE, Holsti L, Haley DW, Oberlander T, Weinberg J, Solimano A, Whitfield MF, Fitzgerald C, Yu W. Neonatal procedural pain exposure predicts lower cortisol and behavioral reactivity in preterm infants in the NICU. Pain. 2005 Feb;113(3):293-300. doi: 10.1016/j.pain.2004.10.020.
citation: Harrison D, Loughnan P, Manias E, Smith K, Johnston L. Effect of concomitant opioid analgesics and oral sucrose during heel lancing. Early Hum Dev. 2011 Feb;87(2):147-9. doi: 10.1016/j.earlhumdev.2010.11.008. Epub 2010 Dec 8.