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Pilot Study of Sucrose to Reduce Pain in Sick Babies

Sponsor
Children's Hospital of Eastern Ontario (Other)
Overall Status
Terminated
CT.gov ID
NCT01438008
Collaborator
University of Ottawa (Other)
9
Enrollment
1
Location
2
Arms
52
Actual Duration (Months)
0.2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: 24% sucrose po solution
  • Drug: Placebo po
 Phase 4

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
9 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Be Sweet to Sick Babies: Analgesic Effects of Oral Sucrose and Concomitant Opioid Analgesics; a Pilot Randomized Controlled Trial
Actual Study Start Date :
May 1, 2012
Actual Primary Completion Date :
Sep 1, 2016
Actual Study Completion Date :
Sep 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Sucrose 24% po

24% sucrose solution. The Children's Hospital of Eastern Ontario (CHOE) pharmacy department will provide syringes labeled "NICU Pain Relief Study" containing a maximum dose of 1 mL of a 24% sucrose solution

Drug: 24% sucrose po solution
CHEO pharmacy department will provide syringes labeled "NICU Pain Relief Study" containing a maximum of 1 ml dose of a 24% sucrose solution. 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. The total amount of the study solution will be divided into a maximum of 5 aliquots and administered throughout the procedure at two minutes prior to the heel lance, immediately prior to the heel lance, and two-minutely intervals until completion of the procedure.
Other Names:
  • CHEO Sucrose

    		•
    Placebo Comparator: Placebo po

    The CHEO pharmacy department will provide a syringe labeled "NICU Pain Relief Study" containing a maximum of 1 ml dose of water (contents almost identical in color, consistency and odor to the sucrose solution) in identical packagings

    Drug: Placebo po
    CHEO pharmacy department will provide syringes labeled "NICU Pain Relief Study" containing a maximum of 1 ml dose of water (almost identical in color, consistency and odor placebo to the sucrose solution in identical packaging) The total amount of the study solution will be divided into 5 aliquots and administered throughout the procedure at two minutes prior to the heel lance, immediately prior to the heel lance, and two-minutely intervals until completion of the procedure
    Other Names:
  • Baxter sterile water

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Premature Infant Pain Profile (PIPP) [Baseline, day one of blood test]

      The Premature Infant Pain Profile (PIPP), a validated seven-indicator multidimensional pain assessment tool which is extensively used in neonatal pain research. The scale consists of seven indicators including assessment of gestational age and behavioural state (contextual indicators), heart rate and oxygen saturation (physiological indicators), and facial actions-brow bulge, eye squeeze, and nasolabial furrow (behavioural indicators), which are scored on a 0-3 scale and added for a total score of 0-21 Facial expression scores were also recorded on a 0-4 scale using a modified Neonatal Facial Coding System (NFCS) at 30, and 60 seconds following the beginning of the procedure. The modified NFCS coded for the presence (1) or absence (0) of the 4 most common facial expressions in response to acute pain (brow bulge, eye squeeze, nasolabial furrow, and stretch open mouth). High values on both of these scales represent worse outcome (i.e higher pain intensity).

    Secondary Outcome Measures

    1. Total Crying Time [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.]

      Cry duration is a useful method to determine infant distress in general and to evaluate pain in the infant's environmental context.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Children's Hospital of Eastern Ontario Ottawa Ontario Canada K1H 8L1

    Sponsors and Collaborators

    • Children's Hospital of Eastern Ontario
    • University of Ottawa

    Investigators

    • Principal Investigator: Denise Harrison, PhD, Children's Hospital of Eastern Ontario

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Denise Harrison, Endowed Chair in Nursing Care of Children, Youth and Families, Children's Hospital of Eastern Ontario
    ClinicalTrials.gov Identifier:
    NCT01438008
    Other Study ID Numbers:
    • 123942
    First Posted:
    Sep 21, 2011
    Last Update Posted:
    Oct 19, 2020
    Last Verified:
    Sep 1, 2020
    Keywords provided by Denise Harrison, Endowed Chair in Nursing Care of Children, Youth and Families, Children's Hospital of Eastern Ontario
    Sucrose
    Pain

    Study Results

    Participant Flow

    Recruitment Details Between June 2012 and September 2015, 73 infants admitted in the NICU were assessed for eligibility, 50 (69%) were ineligible, of the 23 (32%) infants that were approached, 7 (3%) declined to participate, 16 (70%) provided consent.
    Pre-assignment Detail Consent was obtain for 16 infants to participate, 7 (44%) were not randomized (prior to data collection n=3 infants were weaned off fentanyl, n=3 infants were discharged/transferred, n=1 medical team refused). 9 (12%) infants were randomized. 4 infants were allocated to sucrose and 5 infants were allocated to water.
    Arm/Group Title Sucrose 24% po Placebo po
    Arm/Group Description 24% sucrose solution. The CHEO pharmacy department will provide syringes labeled "NICU Pain Relief Study" containing a maximum dose of 1 mL of a 24% sucrose solution 24% sucrose po solution: CHEO pharmacy department will provide syringes labeled "NICU Pain Relief Study" containing a maximum of 1 ml dose of a 24% sucrose solution. 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. The total amount of the study solution will be divided into a maximum of 5 aliquots and administered throughout the procedure at two minutes prior to the heel lance, immediately prior to the heel lance, and two-minutely intervals until completion of the procedure. The CHEO pharmacy department will provide a syringe labeled "NICU Pain Relief Study" containing a maximum of 1 ml dose of water (contents almost identical in color, consistency and odor to the sucrose solution) in identical packagings Placebo po: CHEO pharmacy department will provide syringes labeled "NICU Pain Relief Study" containing a maximum of 1 ml dose of water (almost identical in color, consistency and odor placebo to the sucrose solution in identical packaging) The total amount of the study solution will be divided into 5 aliquots and administered throughout the procedure at two minutes prior to the heel lance, immediately prior to the heel lance, and two-minutely intervals until completion of the procedure
    Period Title: Overall Study
    STARTED 4 5
    COMPLETED 4 5
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Sucrose 24% po Placebo po Total
    Arm/Group Description 24% sucrose solution. The CHEO pharmacy department will provide syringes labeled "NICU Pain Relief Study" containing a maximum dose of 1 mL of a 24% sucrose solution 24% sucrose po solution: CHEO pharmacy department will provide syringes labeled "NICU Pain Relief Study" containing a maximum of 1 ml dose of a 24% sucrose solution. 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. The total amount of the study solution will be divided into a maximum of 5 aliquots and administered throughout the procedure at two minutes prior to the heel lance, immediately prior to the heel lance, and two-minutely intervals until completion of the procedure. The CHEO pharmacy department will provide a syringe labeled "NICU Pain Relief Study" containing a maximum of 1 ml dose of water (contents almost identical in color, consistency and odor to the sucrose solution) in identical packagings Placebo po: CHEO pharmacy department will provide syringes labeled "NICU Pain Relief Study" containing a maximum of 1 ml dose of water (almost identical in color, consistency and odor placebo to the sucrose solution in identical packaging) The total amount of the study solution will be divided into 5 aliquots and administered throughout the procedure at two minutes prior to the heel lance, immediately prior to the heel lance, and two-minutely intervals until completion of the procedure Total of all reporting groups
    Overall Participants 4 5 9
    Age (days) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [days]
    17.5
    10.0
    10.0
    Age (gestational age (days)) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [gestational age (days)]
    261.5
    236.0
    236.0
    Sex: Female, Male (Count of Participants)
    Female
    3
    75%
    2
    40%
    5
    55.6%
    Male
    1
    25%
    3
    60%
    4
    44.4%
    Type of Procedure (Count of Participants)
    Heel lance
    4
    100%
    4
    80%
    8
    88.9%
    Naso/oro gastric insertion
    0
    0%
    1
    20%
    1
    11.1%
    Duration of Procedure (seconds) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [seconds]
    281
    380
    301
    Type of opioid administered (Count of Participants)
    Morphine
    1
    25%
    1
    20%
    2
    22.2%
    Fentanyl
    3
    75%
    4
    80%
    7
    77.8%
    Previous use of sucrose (Count of Participants)
    Yes
    1
    25%
    4
    80%
    5
    55.6%
    No
    1
    25%
    1
    20%
    2
    22.2%
    Unknown
    2
    50%
    0
    0%
    2
    22.2%

    Outcome Measures

    1. Primary Outcome
    Title Premature Infant Pain Profile (PIPP)
    Description The Premature Infant Pain Profile (PIPP), a validated seven-indicator multidimensional pain assessment tool which is extensively used in neonatal pain research. The scale consists of seven indicators including assessment of gestational age and behavioural state (contextual indicators), heart rate and oxygen saturation (physiological indicators), and facial actions-brow bulge, eye squeeze, and nasolabial furrow (behavioural indicators), which are scored on a 0-3 scale and added for a total score of 0-21 Facial expression scores were also recorded on a 0-4 scale using a modified Neonatal Facial Coding System (NFCS) at 30, and 60 seconds following the beginning of the procedure. The modified NFCS coded for the presence (1) or absence (0) of the 4 most common facial expressions in response to acute pain (brow bulge, eye squeeze, nasolabial furrow, and stretch open mouth). High values on both of these scales represent worse outcome (i.e higher pain intensity).
    Time Frame Baseline, day one of blood test

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Sucrose 24% po Placebo po
    Arm/Group Description 24% sucrose solution. The CHEO pharmacy department will provide syringes labeled "NICU Pain Relief Study" containing a maximum dose of 1 mL of a 24% sucrose solution 24% sucrose po solution: CHEO pharmacy department will provide syringes labeled "NICU Pain Relief Study" containing a maximum of 1 ml dose of a 24% sucrose solution. 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. The total amount of the study solution will be divided into a maximum of 5 aliquots and administered throughout the procedure at two minutes prior to the heel lance, immediately prior to the heel lance, and two-minutely intervals until completion of the procedure. The CHEO pharmacy department will provide a syringe labeled "NICU Pain Relief Study" containing a maximum of 1 ml dose of water (contents almost identical in color, consistency and odor to the sucrose solution) in identical packagings Placebo po: CHEO pharmacy department will provide syringes labeled "NICU Pain Relief Study" containing a maximum of 1 ml dose of water (almost identical in color, consistency and odor placebo to the sucrose solution in identical packaging) The total amount of the study solution will be divided into 5 aliquots and administered throughout the procedure at two minutes prior to the heel lance, immediately prior to the heel lance, and two-minutely intervals until completion of the procedure
    Measure Participants 4 5
    PIPP-R at 30 seconds
    9.5
    10
    PIPP-R at 60 seconds
    9.5
    9
    NFCS at 30 seconds
    1.5
    0
    NFCS at 60 seconds
    2
    0
    2. Secondary Outcome
    Title Total Crying Time
    Description Cry duration is a useful method to determine infant distress in general and to evaluate pain in the infant's environmental context.
    Time Frame 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.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Sucrose 24% po Placebo po
    Arm/Group Description 24% sucrose solution. The CHEO pharmacy department will provide syringes labeled "NICU Pain Relief Study" containing a maximum dose of 1 mL of a 24% sucrose solution 24% sucrose po solution: CHEO pharmacy department will provide syringes labeled "NICU Pain Relief Study" containing a maximum of 1 ml dose of a 24% sucrose solution. 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. The total amount of the study solution will be divided into a maximum of 5 aliquots and administered throughout the procedure at two minutes prior to the heel lance, immediately prior to the heel lance, and two-minutely intervals until completion of the procedure. The CHEO pharmacy department will provide a syringe labeled "NICU Pain Relief Study" containing a maximum of 1 ml dose of water (contents almost identical in color, consistency and odor to the sucrose solution) in identical packagings Placebo po: CHEO pharmacy department will provide syringes labeled "NICU Pain Relief Study" containing a maximum of 1 ml dose of water (almost identical in color, consistency and odor placebo to the sucrose solution in identical packaging) The total amount of the study solution will be divided into 5 aliquots and administered throughout the procedure at two minutes prior to the heel lance, immediately prior to the heel lance, and two-minutely intervals until completion of the procedure
    Measure Participants 4 5
    Median (Inter-Quartile Range) [seconds]
    0
    0

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Sucrose 24% po Placebo po
    Arm/Group Description 24% sucrose solution. The CHEO pharmacy department will provide syringes labeled "NICU Pain Relief Study" containing a maximum dose of 1 mL of a 24% sucrose solution 24% sucrose po solution: CHEO pharmacy department will provide syringes labeled "NICU Pain Relief Study" containing a maximum of 1 ml dose of a 24% sucrose solution. 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. The total amount of the study solution will be divided into a maximum of 5 aliquots and administered throughout the procedure at two minutes prior to the heel lance, immediately prior to the heel lance, and two-minutely intervals until completion of the procedure. The CHEO pharmacy department will provide a syringe labeled "NICU Pain Relief Study" containing a maximum of 1 ml dose of water (contents almost identical in color, consistency and odor to the sucrose solution) in identical packagings Placebo po: CHEO pharmacy department will provide syringes labeled "NICU Pain Relief Study" containing a maximum of 1 ml dose of water (almost identical in color, consistency and odor placebo to the sucrose solution in identical packaging) The total amount of the study solution will be divided into 5 aliquots and administered throughout the procedure at two minutes prior to the heel lance, immediately prior to the heel lance, and two-minutely intervals until completion of the procedure
    All Cause Mortality
    Sucrose 24% po Placebo po
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Sucrose 24% po Placebo po
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/4 (0%) 0/5 (0%)
    Other (Not Including Serious) Adverse Events
    Sucrose 24% po Placebo po
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/4 (0%) 0/5 (0%)

    Limitations/Caveats

    Recruitment for this study was difficult due to the tight inclusion criteria. Although consent was provided for 16 infants to participate, only 9 infants were randomized and studied the results may contribute to systematic review data.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Denise Harrison
    Organization Children's Hospital of Eastern Ontario
    Phone 6137377600 ext 6045
    Email dharrison@cheo.on.ca
    Responsible Party:
    Denise Harrison, Endowed Chair in Nursing Care of Children, Youth and Families, Children's Hospital of Eastern Ontario
    ClinicalTrials.gov Identifier:
    NCT01438008
    Other Study ID Numbers:
    • 123942
    First Posted:
    Sep 21, 2011
    Last Update Posted:
    Oct 19, 2020
    Last Verified:
    Sep 1, 2020