Clinical trial NCT00571636: Continuous Infusion of Fentanyl in Preterm on MV
Official title: Efficacy and Safety of Continuous Infusion of Fentanyl for Pain Control in Preterm Newborn on Mechanical Ventilation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pain
Infant, Premature, Diseases
Respiration; Insufficient or Poor, Newborn
Keywords: Opioids infusion
mechanical ventilation
Lead sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
Sponsor class: OTHER
Collaborators: name: Agenzia Italiana del Farmaco
First posted: 2007-12-12
Enrollment: 128
Sex: ALL
Maximum age (years): 32
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this randomized, double-blind trial is to compare the efficacy and safety of 2 therapeutic regimens of fentanyl administration in a population of preterm newborns of GA \<= 32 weeks in MV:

* Group A) continuous infusion of Fentanyl + open label boluses of Fentanyl;
* Group B) continuous infusion of placebo + open label boluses of Fentanyl.

Detailed description: The primary objective of the study is to evaluate the analgesic superiority of Fentanyl given as 'continuous infusion + boluses' versus 'boluses alone' by comparing pain scores obtained by the application of validated algometric scales for chronic pain (EDIN - Echelle Douleur Inconfort Nouveau-Nè) and acute pain (PIPP- Premature Infant Pain Profile).

The secondary objective of the study is to evaluate the safety equivalence of the above 2 therapeutic regimens by recording:

* Rate of mechanically ventilated newborns at one week of age
* Age at which neonates will reach total enteral feeding
* Age (hours) of first meconium passage
* Incidence of intraventricular haemorrhage (IVH), periventricular leucomalacia (PVL) or death within 28 days of life
* Incidence of bladder globe during the first week of life
* Incidence of hypotension during the first week of life

5.2.1 Pain measurement: during the study phase acute pain will be measured once a day during a heel prick by a validated algometric scale for acute pain (PIPP); chronic pain will be measured 3 times a day by a validated algometric scale for chronic pain (EDIN). Inter-rater reliability has been shown acceptable for both scales (26,27). Moreover, in October 2006 the Coordinating Center organized a theoretical and practical course on the correct application of the PIPP and EDIN scales (26,27) for all the participating centers in order to reduce the inter-Center variability in pain measurement.

The EDIN scores will be recorded in a specific CRF (CRF N°1, p. 15). The PIPP scores will be reported in a specific CRF (CRF N° 1, pp. 8-14).

5.2.2 Painful procedures: the following painful procedures, as well as the action taken to reduce pain, will be recorded in the same CRF (CRF N° 1, pp. 8-14):

* heel pricks
* endotracheal aspirations
* venous blood samplings
* pneumothorax drainage
* peripherally inserted central catheter positioning
* others (specify) 5.2.3 Fentanyl open label boluses administration: all the boluses of open label fentanyl administered according to the criteria reported in paragraph 6.1.1 have to be recorded in a special CRF (CRF N° 1, p. 7).

5.2.4 Instrumental examinations: a heart ultrasound has to be obtained in all newborns in the first week of life in order to diagnose patent ductus arteriosus. Brain ultrasound has to be repeated at 4, 7 days of age and then twice a month or when clinically indicated.

Eligibility criteria: Inclusion Criteria:

* inborn neonates
* preterm neonates ≤ 32+ 6 days weeks gestation
* \< 72 hours of life
* newborns on MV
* within 24 hours from the beginning of MV administered through an endotracheal tube
* 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 4 at 5 minutes of age and/or umbilical arterial pH \< 7.0
* Known genetic or chromosomal disorders
* Severe IVH (\> grade II according to Volpe classification (30))
* Need for post-operative analgesic therapy in the first week of life
* Participation in another clinical trial of any placebo, drug, biological, or device conducted under the provisions of a protocol

Primary outcomes:
measure: The primary efficacy variable for this study will be the pain scores obtained during the study period. Procedural pain will be measured once a day by the PIPP scale. Chronic pain will be evaluated through the application of the EDIN scale 3 times a day.
timeFrame: 7 days
Secondary outcomes:
measure: Rate of MVd newborns at one week of age;Age at which neonates will reach total enteral feeding;Age of first meconium passage;Incidence of IVH, PVL or death within 28 days of life;Incidence of bladder globe and hypotension during the first week of life
timeFrame: until discharge from hospital
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: St'Orsola-Malpighi General Hospital
state: BO
Study officials:
affiliation: St'Orsola-Malpighi General Hospital
name: Gina Ancora, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ancora G, Lago P, Garetti E, Pirelli A, Merazzi D, Mastrocola M, Pierantoni L, Faldella G. Efficacy and safety of continuous infusion of fentanyl for pain control in preterm newborns on mechanical ventilation. J Pediatr. 2013 Sep;163(3):645-51.e1. doi: 10.1016/j.jpeds.2013.02.039. Epub 2013 Apr 10.