Continuous Infusion of Fentanyl in Preterm on MV

Pain Clinical Trial

Official title:

Efficacy and Safety of Continuous Infusion of Fentanyl for Pain Control in Preterm Newborn on Mechanical Ventilation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00571636
• Other study ID #: NEO 01/2005
• Secondary ID: FARM63TMS3
• Status: Completed
• Phase: Phase 3
• First received: December 11, 2007
• Last updated: October 8, 2011
• Start date: December 2007
• Est. completion date: July 2010

Study information

• Verified date: October 2011
• Source: St. Orsola Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines AgencyItaly: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 128
• Est. completion date: July 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 32 Weeks

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infant, Premature, Diseases
• Pain
• Respiration; Insufficient or Poor, Newborn

Intervention

Drug:
• Fentanyl
The experimental drug will be diluted according to each NICU scheme and administered as an attach dose of 1 mcg/kg in 30' followed by continuous i.v. infusion of 1 mcg/kg/h. Infusion of the experimental drug has to begin within 24 hrs from the beginning of MV and has to be continued until the end of MV and not after 7 days of life. If the newborn is still on MV after the 7th day of life he/she will be treated for pain according to local protocols. Open label boluses of Fentanyl during the study phase will be administered, in both groups when the EDIN pain score is > 6 and before performing the following invasive procedures:Peripherally inserted central venous catheter positioning;Re-intubation;Lumbar puncture;Pneumothorax or hydrothorax drainage.
• 5% glucose solution
ev continuous infusion

Locations

Country	Name	City	State
Italy	St'Orsola-Malpighi General Hospital	Bologna	BO

Sponsors (2)

Lead Sponsor	Collaborator
St. Orsola Hospital	Agenzia Italiana del Farmaco

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		7 days	No
Secondary	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		until discharge from hospital	Yes