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Trial registered on ANZCTR


Trial ID
ACTRN12613000652774
Ethics application status
Approved
Date submitted
6/06/2013
Date registered
12/06/2013
Date last updated
12/06/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy of intranasal fentanyl for the treatment of moderate to severe pain in adult patients in the emergency department
Scientific title
Efficacy of intranasal fentanyl for the treatment of moderate to severe pain in adult patients in the emergency department
Secondary ID [1] 282630 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Moderate to severe pain in patients over 18yo presenting to Frankston ED. Pain can be from any cause except as specified by the exclusion criteria. Definition of moderate to severe pain is 6 out of 10 or more (self rated by patient) on a visual analog score, where 0 is no pain and 10 is the worst pain imaginable. 289324 0
Condition category
Condition code
Anaesthesiology 289666 289666 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
fentanyl citrate, concentrated solution of 300mcg/ml.

Dosage will depend on bodyweight. Initially 1.4mcg/kg will be administered intranasally, using an atomiser device attached to a syringe. A subsequent 0.7mcg/kg will be administered 15 minutes after the first dose if the patient is requesting further analgesia.

If at any point the patient requests further analgesia, they will receive standard emergency treatment such as intravenous morphine.

Study drug will be administered at the time of enrolement, and at 15 minutes if requested by patient. Follow up time points will occur at 30 minutes and 60 minutes. The total duration of the study will be 60 minutes.
Intervention code [1] 287297 0
Treatment: Drugs
Comparator / control treatment
N/A
Control group
Uncontrolled

Outcomes
Primary outcome [1] 289747 0
Mean change in Visual Analog Scale pain score (VAS) from pre-administration (T0) to 30 minutes post-administration (T30)
Timepoint [1] 289747 0
T30
Secondary outcome [1] 303174 0
Mean change on Visual Analog Scale (VAS) pain score from pre-administration (T0) to 60 minutes post-administration (T60)
Timepoint [1] 303174 0
T60
Secondary outcome [2] 303175 0
time to analgesia, recorded as time of patient arrival to administration of intranasal fentanyl by treating doctor.
Timepoint [2] 303175 0
this outcome will be assessed at the time of administration of intranasal fentanyl
Secondary outcome [3] 303176 0
intravenous cannulation: treating doctor will be asked whether IV cannulation was required if all analgesia could be given by non parenteral routes, i.e. intranasally or orally.
Timepoint [3] 303176 0
this outcome will be assessed at 60 minutes post-administration of intranasal fentanyl (T60)
Secondary outcome [4] 303177 0
percentage requiring a second dose of fentanyl at T15
Timepoint [4] 303177 0
this outcome will be assessed at 15 minutes post-administration of intranasal fentanyl (T15)
Secondary outcome [5] 303178 0
Patient satisfaction with the amount of analgesia experienced (satisfied, not-satisfied, uncertain)
Timepoint [5] 303178 0
This outcome will be assessed at 15 minutes, 30 minutes and 60 minutes post administration of the first dose of intranasal fentanyl. (T15, T30 and T60)
Secondary outcome [6] 303179 0
Percentage of participants requiring additional analgesia, such as IV morphine - that is, if the patient requests additional analgesia at any time within the 60 minute duration of the study.
Timepoint [6] 303179 0
If at any time within the 60 minute duration of the study a participant requests additional analgesia, this time point will be recorded and will signify the end of the study for the participant. Eg. if the participant requests intravenous morphine at 25 minutes, this will be recorded as the endpoint. No further study assessments will be carried out on the participant.
Secondary outcome [7] 303180 0
adverse event profile, including sedation, systemic AEs, local AEs, allergic reaction etc.
Timepoint [7] 303180 0
At any time prior to T60, if an adverse event is observed

Eligibility
Key inclusion criteria
Age greater or equal to 18 years
Self-report pain severity as being greater than or equal to 6 on the standard 11-point verbal rating scale, where 0 is no pain and 10 is the worst pain imaginable
Medical recommendation for parenteral analgesia (attending doctor’s discretion)
Pain from any cause other than the specific exclusion criteria (see below)
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Known allergy or previous adverse reaction to fentanyl
Use of oral, intranasal or parenteral narcotic analgesia in previous 4 hours (either pre-hospital or in the emergency department) [NB. Pre-hospital use of short-acting inhaled methoxyfluorane alone or non-narcotic analgesics do not constitute an exclusion]
MAO Inhibitor antidepressant use within last 14 days
Haemodynamic instability (eg HR > 120/min or BP < 90 mmHg) with the need for time critical interventions of any type
Suspicion of any of the following medical conditions:
myocardial ischaemia (concern re transient hypotension from fentanyl)
suspected subarachnoid haemorrhage (concern re transient hypotension from fentanyl)
migraine (specific proven therapy)
Relative contraindication to, or anticipated difficulty with nasal administration of medication that may prevent adequate administration or absorption of intranasal medication (eg aberrant nasal anatomy, acute or chronic nasal problems or nasal trauma).
Presence of acute cognitive impairment (any underlying cause)
Schizophrenia or related psychiatric conditions (even if currently well controlled)
History of recreational substance abuse
Inability to understand study explanation or procedures, or to provide informed consent
Pregnancy, breast feeding

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
All eligible patients will be invited to participate. Patient will be verbally consented initally to ensure timely access to analgesia. Written consent will then be obtained.

All enrolled patients will receive the same intervention, and the study will be unblinded and non-randomised.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Subjects will be given a sequential study number in the order that they will be enrolled. Each patient will be allocated the next vial in the pack.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 1093 0
Frankston Hospital - Frankston

Funding & Sponsors
Funding source category [1] 287409 0
Hospital
Name [1] 287409 0
Peninsula Health
Address [1] 287409 0
Peninsula Health
Research Program
P O Box 52
Frankston VIC 3199
Country [1] 287409 0
Australia
Primary sponsor type
Hospital
Name
Peninsula Health
Address
P O Box 52
Frankston VIC 3199
Country
Australia
Secondary sponsor category [1] 286154 0
None
Name [1] 286154 0
Address [1] 286154 0
Country [1] 286154 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289383 0
Peninsula Health Drugs and Therapeutics Committee
Ethics committee address [1] 289383 0
P O Box 52
Frankston VIC 3199
Ethics committee country [1] 289383 0
Australia
Date submitted for ethics approval [1] 289383 0
11/04/2013
Approval date [1] 289383 0
16/05/2013
Ethics approval number [1] 289383 0
HREC/13/PH/21
Ethics committee name [2] 289384 0
Peninsula Health Human Research Ethics Committee
Ethics committee address [2] 289384 0
P O Box 52
Frankston VIC 3199
Ethics committee country [2] 289384 0
Australia
Date submitted for ethics approval [2] 289384 0
26/04/2013
Approval date [2] 289384 0
21/05/2013
Ethics approval number [2] 289384 0
HREC/13/PH/21

Summary
Brief summary
Pain is a common presenting symptom in the emergency department patient population with opioids being the cornerstone of treatment for moderate to severe pain. Fentanyl is a safe and effective opioid drug which is commonly used in adults and children for this indication.
Rapid analgesia is usually effected in emergency patients by administering an opioid via the intravenous route but this can be associated with pain, inconvenience and delay as it requires the insertion of an intravenous cannula.
The intranasal route of administration of opioids offers an attractive alternative as it is non invasive and does not require intravenous access. It also provides an alternative where intravenous access is difficult or not required and where nausea and vomiting prevent oral drug administration. In a number of patients intravenous access may then be completely avoided.
The intranasal (IN) route has increasingly been viewed as an alternative route for drug administration. It is commonly used in the paediatric population where more invasive methods of drug delivery (intravenous or intramuscular) may result in significant discomfort, anxiety and increased stress during a hospital visit. The effective treatment of acute pain in children with intranasal opioids such as fentanyl is well documented. There is also evidence in adult acute and chronic pain settings that fentanyl in analgesic doses by the intranasal route provides effective analgesia.
A significant limitation of using IN fentanyl in the adult population in the hospital setting is the inability to access the concentrated formulation (300mcg/ml). This preparation is more expensive than the widely available standard formulation (50mcg/ml) fentanyl and so is not widely accessible for use. Effective IN analgesia in adults requires the more concentrated formulation of fentanyl due nasal absorption considerations.
This is a non-randomised single group study of IN fentanyl in 150 adult patients with moderate to severe pain from all causes. Patients presenting with pain greater or equal to 6 out of 10 will be given a dose of concentrated (300mcg/ml) IN fentanyl. Pain scores will be taken at regular intervals over 60 minutes. If there is no response by 15 minutes a second dose of fentanyl will be given. If no appreciable pain relief occurs by 30 minutes, standard IV opioid analgesia will be given. The results of this study will provide information on the effectiveness of fentanyl in the treatment of moderate to severe pain in adult ED patients and will allow us to determine future sample sizes for prospective comparative studies of fentanyl to other pain relievers used in the ED.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 40578 0
A/Prof Pamela Rosengarten
Address 40578 0
Frankston Hospital
Department of Emergency Medicine
P O Box 52
Frankston VIC 3133
Country 40578 0
Australia
Phone 40578 0
+61 3 9784 7067
Fax 40578 0
Email 40578 0
prosengarten@phcn.vic.gov.au
Contact person for public queries
Name 40579 0
Dr Eva Hagop
Address 40579 0
Frankston Hospital
Department of Emergency Medicine
P O Box 52
Frankston VIC 3133
Country 40579 0
Australia
Phone 40579 0
+61 3 9784 8833
Fax 40579 0
Email 40579 0
EHagop@phcn.vic.gov.au
Contact person for scientific queries
Name 40580 0
Dr Eva Hagop
Address 40580 0
Frankston Hospital
Department of Emergency Medicine
P O Box 52
Frankston VIC 3133
Country 40580 0
Australia
Phone 40580 0
+61 3 9784 8833
Fax 40580 0
Email 40580 0
EHagop@phcn.vic.gov.au