Analgesic Efficacy of Different Doses of Sucrose During Blood Sampling in Preterm Infants

Pain Clinical Trial

Official title:

Analgesic Efficacy of Different Doses of Sucrose During Blood Sampling in Preterm Infants: Prospective, Randomized, Controlled, Double Blind, Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02859376
• Other study ID #: AOP0066025
• Status: Recruiting
• Phase: N/A
• First received: December 16, 2015
• Last updated: August 3, 2016
• Start date: February 2016
• Est. completion date: December 2016

Study information

• Verified date: August 2016
• Source: University Hospital Padova
• Contact: Teresa Mion, MD
• Phone: +39 049 8213547
• Email: tritrimi[@]gmail.com
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The objective of this trial is to compare the analgesic effect of a single dose of oral sucrose 24% administered two minutes before a blood sampling (either heel prick or vascular puncture) versus multiple doses of oral sucrose 24% administered two minutes before and during the procedure in a population of preterm newborns of Gestational Age ≤ 36+6 weeks hospitalized in Neonatal Intensive Care Unit, using neonatal pain scales (Premature Infant Pain Profile (PIPP), Face, Legs, Activity, Cry, Consolability (FLACC) and indirect Visual Analogue Scale (VAS)) and Skin Conductance (SC) measurement (Pain Monitor).

Description:

This is a controlled, randomized, double blind, (double--dummy) study to evaluate the analgesic efficacy of sucrose. The study staff will evaluate all inborn newborns admitted to the Neonatal Intensive Care Unit (NICU) with a Gestational Age (GA) ≤36+6 weeks; the newborns will be immediately screened for eligibility based upon the pre--defined study inclusion/exclusion criteria.

Then, the parents will be informed about the study and the written informed consent form will be signed. Those eligible will be randomized into the study through computer generated randomization list.

The population of the study consists of premature infants undergoing blood sampling. It is estimated that approximately 144 premature neonates (72 per group either heel prick or venepuncture) will be included in the randomized study.

All eligible neonates whose parents have agreed to participate in the study by signing the informed consent form will be randomized as soon as they are admitted to the NICU.

This study will be conducted in 3 phases:

• Pre--randomization The following items will be obtained: Maternal history including the mother's medical and pregnancy history, prenatal care status; Antenatal analgesics and sedative drugs given to the mother; Estimated GA, birth weight and length. All the data have to be noted on the Case Report Form (CRF);

• Study phase: Premature neonates undergoing blood samples through skin breaking procedures, meeting inclusion criteria, will be randomized as soon as the doctor decision to drown the blood is made, to either sucrose 24% 0,3 mL if ≤ 1000 g or 0,5 mL if > 1000 g two minutes before the skin breaking procedure or sucrose 24% 0,3 mL if ≤ 1000 g or 0,5 mL if > 1000 g two minutes before and during the skin breaking procedure, according to a computer generated randomization list. A trained operator (a nurse or a doctor) will perform heel pricks using an automatic lance (Tenderfoot® micro--preemie for infants < 1000 g and Tenderfoot preemie for infants > 1000 grams) and venipuncture using a butterfly needle 23--25 gauge. Any skin breaking procedure, either heel prick or venipuncture, for each patient will be noted down;; patients will be video--recorded during blood sampling to allow at least two operators to evaluate the analgesic efficacy of the intervention by algometric measurements. In a subgroup of patients skin conductance will also be measured.

Algometric measurements: The pain evaluation will be done visualizing the video of the procedure. Two different evaluators independently will assign the pain score with:

1. Premature Infant Pain Profile (PIPP) at 30 and 60 seconds after the skin puncture

2. Face, Legs, Activity, Cry, Consolability (FLACC) scale at 30 seconds

3. Indirect Visual Analogue Scale (VAS) at 30 seconds for inter--rater agreement. One week later the same evaluators will assign again the pain scores for the intra--rater agreement.

Instrumental PAIN examinations: Pain Monitor is an instrument that measures SC. It detects hand or foot skin conductance gradient, which is directly related to the painful stimuli. The sympathetic nervous system releases acetylcholine that acts on muscarine receptors inducing a sweating and SC increase in response to painful stimuli. Pain monitor is simple to use: tree electrodes positioned on neonate foot sole are connected to the central system. Pain monitor immediately and continuously reacts to stimuli without being influenced neither by hemodynamic variability nor by neuromuscular blocks. The measurement its represented on a compatible computer monitor through a graphic function with SC values expressed in microsiemens on the ordinate axis and time on the abscissa axis. Stressful and painful stimuli related SC variability is represented by peaks and the under peaks area defines pain intensity at detection moment. During monitoring you can note down directly on the graphic every intervention on the patient (medication, blood sample, ect.). Detection can be extrapolated with Excel for statistical analysis.

• Follow--up phase: it will begin from the end of the blood samples. Assessments will continue until hospital discharge.

AE that are ongoing during the study phase as well as clinical outcomes (that are major clinical diagnoses) will be assessed until hospital discharge. Clinical data will be recorded on CRF. In addition the following information will be collected at hospital discharge:

• Number of previous skin breaking procedures

• Number of previous sucrose doses

• Clinical status of the infant

• Duration of hospitalization

• Number of Ventilated Days

• Need for oxygen/monitor at discharge

• Need for supplemental oxygen at 36 weeks post--menstrual age

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 144
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 28 Days

Eligibility

Inclusion Criteria:

• preterm neonates with gestational age ranging from 23+ 0 to 36+ 6 weeks

• undergoing blood sampling (either heel prick or vascular puncture)

• age = 40 week GA + 28 days at the time of blood sampling

• parental written informed consent for participation in the study must be obtained

Exclusion Criteria:

• Evidence of severe birth asphyxia, that is an APGAR score below 5 at 5 minutes of age and/or umbilical arterial pH < 7.0

• Known genetic or chromosomal disorders

• Myopathies and neuropathies interfering with pain assessment by pain scales

• Sedation

• Presence of central catheter allowing blood sampling without skin breaking

• Other painful procedure less than 2 hours before blood sampling

• Physiological instability (more than 6 episodes of bradycardia and/or apnea per day)

• Maternal drug abuse

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Pain

Intervention

Dietary Supplement:
• sucrose 24%
Premature neonates undergoing blood samples through skin breaking procedures, meeting inclusion criteria, will be randomized as soon as the doctor decision to drown the blood is made, to either sucrose 24% 0,3 mL if < 1000 g or 0,5 mL if > 1000 g two minutes BEFORE the skin breaking procedure or sucrose 24% 0,3 mL if < 1000 g or 0,5 mL if > 1000 g two minutes BEFORE and DURING the skin breaking procedure, according to a computer generated randomization list.

Locations

Country	Name	City	State
Italy	University Hospital of Padova	Padova

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Padova

Country where clinical trial is conducted

Italy, 

References & Publications (6)

Cignacco EL, Sellam G, Stoffel L, Gerull R, Nelle M, Anand KJ, Engberg S. Oral sucrose and "facilitated tucking" for repeated pain relief in preterms: a randomized controlled trial. Pediatrics. 2012 Feb;129(2):299-308. doi: 10.1542/peds.2011-1879. Epub 2012 Jan 9. — View Citation

Shah PS, Herbozo C, Aliwalas LL, Shah VS. Breastfeeding or breast milk for procedural pain in neonates. Cochrane Database Syst Rev. 2012 Dec 12;12:CD004950. doi: 10.1002/14651858.CD004950.pub3. Review. — View Citation

Shah VS, Ohlsson A. Venepuncture versus heel lance for blood sampling in term neonates. Cochrane Database Syst Rev. 2011 Oct 5;(10):CD001452. doi: 10.1002/14651858.CD001452.pub4. Review. — View Citation

Simonse E, Mulder PG, van Beek RH. Analgesic effect of breast milk versus sucrose for analgesia during heel lance in late preterm infants. Pediatrics. 2012 Apr;129(4):657-63. doi: 10.1542/peds.2011-2173. Epub 2012 Mar 5. — View Citation

Stevens B, Yamada J, Lee GY, Ohlsson A. Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database Syst Rev. 2013 Jan 31;(1):CD001069. doi: 10.1002/14651858.CD001069.pub4. Review. Update in: Cochrane Database Syst Rev. 2016;7:CD001069. — View Citation

Yin T, Yang L, Lee TY, Li CC, Hua YM, Liaw JJ. Development of atraumatic heel-stick procedures by combined treatment with non-nutritive sucking, oral sucrose, and facilitated tucking: a randomised, controlled trial. Int J Nurs Stud. 2015 Aug;52(8):1288-99. doi: 10.1016/j.ijnurstu.2015.04.012. Epub 2015 Apr 23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of analgesic efficacy Premature Infant Pain Profile (PIPP)	The primary outcome of this study will be to evaluate the analgesic efficacy of sucrose 24% administration (single versus multiple doses) during blood sampling using Premature Infant Pain Profile (PIPP).	2 minutes before, at the moment of the skin puncture, and at 30, 60 and 120 seconds after the skin puncture	No
Secondary	Change of analgesic efficacy Face, Legs, Activity, Cry, Consolability (FLACC)	The analgesic efficacy of sucrose 24% administration (single Vs multiple doses) during blood sampling using Face, Legs, Activity, Cry, Consolability (FLACC)	at 30 and 120 seconds after the skin puncture	No
Secondary	Change of analgesic efficacy Visual Analogue Scale (VAS)	The analgesic efficacy of sucrose 24% administration (single Vs multiple doses) during blood sampling using indirect Visual Analogue Scale (VAS).	at 30 and 120 seconds after the skin puncture	No
Secondary	Change of analgesic efficacy Pain Monitor (skin electrical conductance)	The analgesic efficacy of sucrose 24% administration (single Vs multiple doses) during blood sampling using Pain Monitor (skin electrical conductance)	2 minutes before, at the moment of the skin puncture, and at 30, 60 and 120 seconds after the skin puncture	No
Secondary	Pain evaluation during heel prick Vs vascular puncture PIPP	Pain evaluation during heel prick Vs vascular puncture will be performed using PIPP scale	Through study completion, an average of 1 year	No
Secondary	Pain evaluation during heel prick Vs vascular puncture FLACC	Pain evaluation during heel prick Vs vascular puncture will be performed using FLACC scale	Through study completion, an average of 1 year	No
Secondary	Pain evaluation during heel prick Vs vascular puncture VAS	Pain evaluation during heel prick Vs vascular puncture will be performed using VAS scale	Through study completion, an average of 1 year	No
Secondary	Pain evaluation during heel prick Vs vascular puncture Pain Monitor (skin electrical conductance)	Pain evaluation during heel prick Vs vascular puncture will be performed using Pain Monitor (skin electrical conductance)	Through study completion, an average of 1 year	No
Secondary	Intra--hospital outcome Mechanical Ventilation (MV) duration	Intra--hospital outcome MV duration	Through study completion, an average of 1 year	No
Secondary	Intra--hospital outcome non-Invasive MV (nIMV) duration	Intra--hospital outcome nIMV duration	Through study completion, an average of 1 year	No
Secondary	Intra--hospital outcome oxygen dependence duration	Intra--hospital outcome oxygen dependence	Through study completion, an average of 1 year	No
Secondary	Intra--hospital outcome rate of Bronchopulmonary Dysplasia (BPD)	Intra--hospital outcome rate of BPD	Through study completion, an average of 1 year	No
Secondary	Intra--hospital outcome rate of Pneumothorax (PNX)	Intra--hospital outcome rate of PNX	Through study completion, an average of 1 year	No
Secondary	Intra--hospital outcome rate of Patent ductus arteriosus (PDA)	Intra--hospital outcome rate of PDA	Through study completion, an average of 1 year	No
Secondary	Intra--hospital outcome incidence Intraventricular hemorrhage (IVH)/ Periventricular leukomalacia (PVL)	Intra--hospital outcome incidence of IVH/PVL	Through study completion, an average of 1 year	No
Secondary	Intra--hospital outcome incidence death within 28 days of life	Intra--hospital outcome incidence of death within 28 days of life	within 28 days of life	No
Secondary	Intra--hospital outcome incidence hydrocephalus	Intra--hospital outcome incidence of hydrocephalus	Through study completion, an average of 1 year	No
Secondary	Intra--hospital outcome time to Full Enteral Feeding (FEF)	Intra--hospital outcome time to FEF	Through study completion, an average of 1 year	No
Secondary	Intra--hospital outcome rate of Necrotizing Enterocolitis (NEC)	Intra--hospital outcome rate of NEC (all stages according to the modified Bell's criteria)	Through study completion, an average of 1 year	No
Secondary	Intra--hospital outcome rate of proved sepsis	Intra--hospital outcome rate of proved sepsis	Through study completion, an average of 1 year	No
Secondary	Intra--hospital outcome rate of suspected sepsis	Intra--hospital outcome rate of suspected sepsis	Through study completion, an average of 1 year	No
Secondary	Intra--hospital outcome rate of Retinopathy of Prematurity (ROP)	Intra--hospital outcome rate of ROP	Through study completion, an average of 1 year	No
Secondary	Intra--hospital outcome time to regain birth weight	Intra--hospital outcome time to regain birth weight	Through study completion, an average of 1 year	No
Secondary	Intra--hospital outcome hospitalization length	Intra--hospital outcome hospitalization length	Through study completion, an average of 1 year	No
Secondary	Intra--hospital outcome incidence hospital discharge without major morbidities	Intra--hospital outcome incidence of hospital discharge without major morbidities	Through study completion, an average of 1 year	No
Secondary	Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)	Safety [achieved by monitoring and registering adverse events (AEs), serious adverse events (SAEs) even those unexpected (SUSARs), and measuring vital signs]	Through study completion till patient discharge, an average of 1 year	Yes