Continuous Infusion of Fentanyl in Preterm on MV - Full Text View

Sponsored by:	St. Orsola Hospital
Information provided by:	St. Orsola Hospital
ClinicalTrials.gov Identifier:	NCT00571636

Purpose

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.

Condition	Intervention	Phase
Pain Infant, Premature Respiration, Artificial Analgesia	Drug: Fentanyl	Phase III

Drug Information available for: Fentanyl Citrate Fentanyl

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Efficacy and Safety of Continuous Infusion of Fentanyl for Pain Control in Preterm Newborn on Mechanical Ventilation

Further study details as provided by St. Orsola Hospital:

Primary Outcome Measures:

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. [ Time Frame: 7 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 [ Time Frame: until discharge from hospital ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	600
Study Start Date:	May 2007
Estimated Study Completion Date:	May 2010

Arms	Assigned Interventions
1: Active Comparator Patients assigned to this arm will receive continuous infusion of fentanyl + open label boluses of Fentanyl if necessary.	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.
2: Placebo Comparator Patients assigned to this arm will receive continuous infusion of placebo+ open label boluses of Fentanyl if necessary.	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.

Arms

Assigned Interventions

1: Active Comparator

Patients assigned to this arm will receive continuous infusion of fentanyl + open label boluses of Fentanyl if necessary.

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.

2: Placebo Comparator

Patients assigned to this arm will receive continuous infusion of placebo+ open label boluses of Fentanyl if necessary.

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.

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

Ages Eligible for Study:	up to 32 Weeks
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00571636

Contacts

Contact: Gina Ancora, Doctor

+390516364463

gina.ancora@unibo.it

Locations

Italy, BO
St'Orsola-Malpighi General Hospital	Recruiting
Bologna, BO, Italy, 40138
Contact: Gina Ancora, Doctor +396364463 gina.ancora@unibo.it

Sponsors and Collaborators

St. Orsola Hospital

Investigators

Principal Investigator:

Gina Ancora, Doctor

St'Orsola-Malpighi General Hospital

More Information

Responsible Party:	Unit of Neonatology; Woman Child Adolescent Health Department University Bologna ( Gina Ancora MD )
Study ID Numbers:	NEO 01/2005, FARM63TMS3
Study First Received:	December 11, 2007
Last Updated:	December 11, 2007
ClinicalTrials.gov Identifier:	NCT00571636
Health Authority:	Italy: The Italian Medicines Agency; Italy: Ethics Committee

Keywords provided by St. Orsola Hospital:

Opioids infusion

Study placed in the following topic categories:

Fentanyl
Pain

Additional relevant MeSH terms:

Anesthetics, Intravenous
Physiological Effects of Drugs
Central Nervous System Depressants
Anesthetics
Narcotics
Pharmacologic Actions
Adjuvants, Anesthesia

Sensory System Agents
Anesthetics, General
Therapeutic Uses
Analgesics
Peripheral Nervous System Agents
Central Nervous System Agents
Analgesics, Opioid

ClinicalTrials.gov processed this record on January 13, 2009