Clinical trial NCT02914678: Is There an Ideal Dose of Intravenous Fentanyl in the Prehospital Setting
Official title: Is There an Ideal Dose of Intravenous Fentanyl in the Prehospital Setting: A Prospective Cluster-randomized Comparison of 2 vs. 3 μg/kg/Transport
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Pain
Keywords: Emergency Medical Services
Analgesics
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Central Denmark Region
First posted: 2016-09-26
Enrollment: 7093
Sex: ALL
Maximum age (years): 110
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In a previous study the investigators evaluated the apparent efficacy and safety of intravenous fentanyl administered by ambulance personnel and found that 58.4% (CI 56.4-60.4) out of 2348 prehospital patients treated with fentanyl still experienced moderate to severe pain \[numeric rating scale (NRS, 0-10) \> 3\] at hospital arrival. The number of patients with possible fentanyl-related side effects was low.

Therefore, the aim of the present study is to explore the efficacy and safety of a liberalized pain treatment protocol for ambulance personnel (a total of 3 μg/kg per transport) compared with existing restrictive protocol (a total of 2 μg/kg per transport). The investigators hypothesize that:

* A higher proportion of patients will experience sufficient pain relief at hospital admission (NRS \< 4) using the liberalized protocol and
* There will be no differences in the proportion of potential fentanyl related side-effects are observed.

Detailed description: A prospective cluster-randomized trial observing proportional differences in sufficient pain relief at hospital admission (NRS \< 4) and potential fentanyl related side-effects between patients treated by ambulance personnel applying either:

* a more liberal treatment approach (a total of 3 μg/kg per transport) or
* existing treatment approach (a total of 2 μg/kg per transport).

The Ambulance stations and their affiliated ambulance personnel are stratified into 5 clusters according to size/average transports per month and randomized to either liberal or existing treatment approach within each cluster. As patients are not randomized on an individual level baseline differences between the two groups and its patients are adjusted statistically with relevant confounders on 3 overall levels:

1. Patients: Charlson Comorbidity Index Score, main overall diagnose category, inhospital surrogate measures of disease severity (intensive care unit admission and 30-day mortality).
2. Ambulance personnel: Years of experience and preinterventional cumulative fentanyl administration and
3. Ambulance stations and geographical factors: prehospital time measures and geographical distance from site of emergency to hospital.

These covariates are obtained from the Danish National Patient Registry, the Danish Civil Registration System and the electronic prehospital patient journal.

Eligibility criteria: Inclusion Criteria:

* Patients with acute pain treated with intravenous fentanyl by ambulance personnel

Exclusion Criteria:

* Reduced conscious level (GCS \< 15) before initiation of fentanyl treatment
* Reduced respiratory rate (\< 10/minute) before initiation of fentanyl treatment
* Patient weight \< 30 kg
* Known opioid allergy
* Women in labour
* Chronic pain conditions

Primary outcomes:
measure: Proportion of patients with sufficient pain relief (NRS < 4) at hospital arrival
timeFrame: Up to 6 hours
Secondary outcomes:
measure: Proportion of patients with reduced Glasgow Coma Scale (<15) after fentanyl administration and at any given point during transport
timeFrame: Up to 6 hours
measure: Proportion of patients with reduced respiratory rate (<10/minute) after fentanyl administration and at any given point during transport
timeFrame: Up to 6 hours
measure: Proportion of patients with reduced peripheral oxygen saturation (< 90%) after fentanyl administration and at any given point during transport
timeFrame: Up to 6 hours
measure: Proportion of patients with hypotension after fentanyl administration and at any given point during transport
timeFrame: Up to 6 hours
Other outcomes:
Locations:
Study officials:
affiliation: University of Aarhus
name: Kristian Friesgaard, MD, PhD Student
role: PRINCIPAL_INVESTIGATOR
affiliation: Aarhus University Hospital
name: Lone Nikolajsen, DmSc
role: STUDY_CHAIR
affiliation: Aarhus University Hospital
name: Hans Kirkegaard, Professor
role: STUDY_CHAIR
affiliation: North Denmark Region
name: Erika Frischknecht Christensen, Professor
role: STUDY_CHAIR
affiliation: Central Denmark Region
name: Matthias Giebner, MD
role: STUDY_CHAIR
affiliation: Central Denmark Region
name: Claus-Henrik Rasmussen, MD
role: STUDY_CHAIR
References:
citation: Friesgaard KD, Nikolajsen L, Giebner M, Rasmussen CH, Riddervold IS, Kirkegaard H, Christensen EF. Efficacy and safety of intravenous fentanyl administered by ambulance personnel. Acta Anaesthesiol Scand. 2016 Apr;60(4):537-43. doi: 10.1111/aas.12662. Epub 2015 Nov 27.
citation: Lynge E, Sandegaard JL, Rebolj M. The Danish National Patient Register. Scand J Public Health. 2011 Jul;39(7 Suppl):30-3. doi: 10.1177/1403494811401482.
citation: Schmidt M, Pedersen L, Sorensen HT. The Danish Civil Registration System as a tool in epidemiology. Eur J Epidemiol. 2014 Aug;29(8):541-9. doi: 10.1007/s10654-014-9930-3. Epub 2014 Jun 26.
citation: Friesgaard KD, Kirkegaard H, Rasmussen CH, Giebner M, Christensen EF, Nikolajsen L. Prehospital intravenous fentanyl administered by ambulance personnel: a cluster-randomised comparison of two treatment protocols. Scand J Trauma Resusc Emerg Med. 2019 Feb 7;27(1):11. doi: 10.1186/s13049-019-0588-4.