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Trial registered on ANZCTR

Registration number

ACTRN12615000872538

Ethics application status

Approved

Date submitted

15/06/2015

Date registered

21/08/2015

Date last updated

6/06/2016

Type of registration

Prospectively registered

Titles & IDs

Public title

Comparing two different concentrations of Intranasal Fentanyl in adults presenting to Frankston Emergency Department with moderate to severe pain.

Scientific title

A prospective randomized study comparing the efficacy of two different concentrations of Intranasal Fentanyl: the standard formulation (50mcg/mL) and the concentrated formulation (300mcg/mL) in adults presenting to Frankston Emergency Department (ED) with moderate to severe pain.

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

U1111-1171-1957

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

moderate to severe pain

Condition category

Condition code

Anaesthesiology

Pain management

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Intranasal Fentanyl Standard Formulation (50mcg/mL)
Single Dose, administered by treating doctor immediately on arrival (patients with moderate to severe pain with pain score greater than or equal to 6 ). Administration of the medication will be witnessed by a nurse as well.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Intranasal Fentanyl Concentrated Formulation (300mcg/mL)
Single Dose, administered by treating doctor immediately on arrival (patients with moderate to severe pain - pain sore greater than or equal to 6 ). Administration of the medication will be witnessed by a nurse as well.

Control group

Dose comparison

Outcomes

Primary outcome [1]

Mean change in Visual Analog Scale (VAS) pain score from pre-administration (T0) to 30 minutes post-administration (T30) in the Standard Intranasal Fentanyl (SINF) and Concentrated Intranasal Fentanyl (CINF) groups, and the difference in the means between the two groups. Composite outcome. Assessed from the patient scored VAS recorded on the data collection form.

Timepoint [1]

Pain score (VAS) at 30 minutes post analgesia.

Secondary outcome [1]

Mean change in Visual Analog Scale pain score from pre-administration (T0) to 15 minutes (T15) and 60 minutes (T60) post-administration and the difference in the means between the two groups.
Composite outcome. Assessed from the patient scored VAS recorded on the data collection form.

Timepoint [1]

Pain score (VAS) at 15 and 60 minutes post analgesia.

Secondary outcome [2]

Percentage requiring an additional dose of fentanyl at T15, and the difference between the two groups. Composite outcome. Assessed from the data recorded by the investigator on the data collection form.

Timepoint [2]

Additional INF at 15 minutes post analgesia.

Secondary outcome [3]

Compare Adverse event profiles in the two groups. Examples of known adverse events are: Over-sedation. This will be monitored by the treating doctor, using the Ramsay sedation scale. Nausea and vomiting. These will be monitored by the study doctor as per standard patient care and anti-emetics may be indicated. Assessed from the data recorded by the investigator on the data collection form.

Timepoint [3]

any time an adverse event occurs from the time of drug administration until T60

Eligibility

Key inclusion criteria

1. Age 18 years to 75 years of age
2. Self-report pain severity as being 6 or more on the standard 10 point verbal rating scale (0 is none, 10 is worst pain imaginable)
3. Medical recommendation for parenteral analgesia (treating doctor’s discretion)
4. Pain from any cause other than the 3 specific exclusions (see below)

Minimum age

18 Years

Maximum age

75 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

1. Known allergy or previous adverse reaction to fentanyl
2. Patients over 75 years of age
3. Use of oral, intranasal, transdermal 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]
4. MAO Inhibitor antidepressant use within last 14 days
5. Myasthenia gravis
6. Haemodynamic instability (eg HR over 120/min or BP under 90 mmHg) with the need for time critical interventions of any type
7. 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

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Once patient consent is obtained, the patient will be randomised into Group A (Standard INF, 50 mcg/mL) or Group B (Concentrated INF, 300 mcg/mL). The patient randomization list is prepared in advance by a member of the research team who will have no contact with patients and have no role in assigning patients to treatment groups. The randomization list is prepared using a computer-generated programme. A sealed envelope attached to each study pack will contain the allocation group, and study packs will be used sequentially.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

The randomization list was prepared using a computer-generated programme.

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Phase

Type of endpoint/s

Efficacy

Statistical methods / analysis

Baseline data including age, sex, weight and diagnosis will be described as median with interquartile range and number with percentage as appropriate. Pain and sedation scores at each time point will be described as median with interquartile range. Change in VAS score from T0 to each other time point will be described as mean reduction (with ‘positive’ being shift towards the left of the scale) in millimetres with 95% confidence interval. The difference in the mean VAS reduction scores between the two groups will be assessed using a Mann Whitney U test. Change in sedation scores will be described as median change with interquartile range. The other categorical outcomes of descriptions of amount of change and satisfaction will be described as number and percentage, as will be adverse events of different types. Some comparison of outcome measures between those who received only the initial 1.4 mcg/kg fentanyl dose and those who received the additional 0.7 mcg/kg dosage at T15 may be performed depending on frequency of the latter dosage addition.
Sample size calculations: There is general literature agreement that the clinically significant reduction in severe pain score is between 15-30 mm on the 10cm visual analog scale. Based on the available literature and the mean change and standard deviation derived from an earlier pilot study, power of 0.8, alpha of 0.05, a sample of 45 patients per group would be required to detect a difference in reduction of VAS score by 15 mm. Recruitment of 110 patients (55 per group) would allow a further 20% 'leeway' to cover the patient drop-outs, incomplete data etc.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

1/09/2015

Actual

15/03/2016

Date of last participant enrolment

Anticipated

30/08/2017

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

110

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Frankston Hospital - Frankston

Recruitment postcode(s) [1]

3199 - Frankston

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Peninsula Health

Address [1]

P O Box 52 Frankston VIC 3199

Country [1]

Australia

Primary sponsor type

Individual

Name

A/Prof Pamela Rosengarten

Address

Peninsula Health, Frankston Hospital Emergency Department
P O Box 52 Frankston VIC 3199

Country

Australia

Secondary sponsor category [1]

Individual

Name [1]

Dr Kishan Ajjampur

Address [1]

Peninsula Health, Frankston Hospital Emergency Department
P O Box 52 Frankston VIC 3199

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Peninsula Health Human Research Ethics Committee

Ethics committee address [1]

Mount Eliza Centre
P O Box 192
Mt. Eliza 3930

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

19/06/2015

Approval date [1]

13/01/2016

Ethics approval number [1]

HREC/15/PH/17

Summary

Brief summary

Pain is a common presenting symptom in the emergency department. For moderate to severe pain, standard treatment is an intravenously administered opioid. 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. 
IN Fentanyl is already 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. For adults who require larger doses of fentanyl, there is a concentrated version available (CINF), hower it is not generally used in emergency departments due to its cost. (An ampoule of concentrated INF (300mcg/mL) is $28.14 and the standard INF (50mcg/mL) is 56 cents. 
We have recently completed a pilot study of concentrated INF in 41 adult patients presenting to Frankston ED with moderate to severe pain. (CINF was specifically purchased for this study funded by a grant by the PHREC). Our results showed that CINF was a safe, well tolerated and efficacious in this patient population. 
The standard INF which is inexpensive and widely available has not been studied in adults in the acute setting as has been done in children. 
We are proposing a randomised equivalence study of CINF versus the SINF, which is readily available in the ED at a fraction of the cost. If equivalence is proven then standard concentration can be recommended for IN use in adults.
A similar study was performed by Borland et al. in children and found that the two formulations of IN fentanyl were equally effective at reducing pain scores.
Hypothesis: standard intranasal fentanyl (SINF) and concentrated intranasal fentanyl (CINF) are equally effective and safe in reducing moderate to strong pain in adult patients in the ED.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

A/Prof Pamela Rosengarten

Address

Frankston Hospital, Emergency department
P O Box 52
Frankston Vic 3199

Country

Australia

Phone

+61 3 9784 1682

Fax

prosengarten@phcn.vic.gov.au

Contact person for public queries

Name

Pamela Rosengarten

Address

Frankston Hospital, Emergency Department
P O Box 52
Frankston, VIC 3199

Country

Australia

Phone

+61 3 97847777

Fax

prosengarten@phcn.vic.gov.au

Contact person for scientific queries

Name

Pamela Rosengarten

Address

Frankston Hospital, Emergency Department
P O Box 52
Frankston, VIC 3199

Country

Australia

Phone

+61 3 9784 1682

Fax

prosengarten@phcn.vic.gov.au

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

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