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Trial registered on ANZCTR

Registration number

ACTRN12610000588099

Ethics application status

Approved

Date submitted

2/06/2010

Date registered

21/07/2010

Date last updated

26/02/2014

Type of registration

Prospectively registered

Titles & IDs

Public title

Comparison of the effectiveness of three oral analgesic combinations in adults presenting to the Emergency Department with moderate pain from acute limb injury.

Scientific title

A double blind randomised controlled trial assessing the analgesic equivalency of oxycodone, paracetamol and ibuprofen with codeine, paracetamol and ibuprofen or paracetamol and ibuprofen alone in moderate pain from musculoskeletal limb injuries presenting to the emergency department.

Secondary ID [1]

No secondary ID present

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

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

analgesia

moderate pain

comparative analgesic effectiveness

emergency medicine

Condition category

Condition code

Injuries and Accidents

Other injuries and accidents

Anaesthesiology

Pain management

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Arm 1) oxycodone 10 mg oral tablet with paracetamol 1000 mg oral tablet with ibuprofen 400 mg oral tablet administered simultaneously as a single dose
Arm 2) codeine 60 mg oral tablet with paracetamol 1000 mg oral tablet with ibuprofen 400 mg oral tablet administered simultaneously as a single dose

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

paracetamol 1000 mg oral tablet with ibuprofen 400 mg oral tablet with thiamine 200 mg oral tablet as a single dose

Control group

Active

Outcomes

Primary outcome [1]

Minimum fall in pain score of at least 20 mm on 100 mm visual analog scale from baseline pain score taken at triage.

Timepoint [1]

Change in pain score from baseline compared to pain scores at 15, 30, 45 and 60 minutes post analgesia adminstration

Secondary outcome [1]

Use of rescue analgesia as assessed by lack of fall in pain score on visual analog scale administered by study researcher

Timepoint [1]

60 minutes post-analgesia administration

Secondary outcome [2]

Patient satisfaction with analgesia regimen assessed at end of study period by study researcher asking subject the degree of satisfaction on a three point satisfaction scale: 1) satisfied 2) not satisfied 3) unsure

Timepoint [2]

60 minutes post-analgesia administration

Secondary outcome [3]

Patient ability to indentify drug regimen prescribed to them. Subjects will be asked by a study investigator whether they think they received:
1) Paracetamol Ibuprofen and Thiamine
2) Paracetamol Ibuprofen and Oxycodone
3) Paracetamol Ibuprofen and Codeine

Timepoint [3]

60 minutes post-analgesia administration

Eligibility

Key inclusion criteria

1) Adult patients greater than or equal to18 years old and less than or equal to 75 years old AND
2) Limb injury within the preceding 48 hours AND
3) Initial verbal pain score elicited by the Triage Nurse of greater than 3/10 to less than or equal to 7/10 (ie 4 to 7/10)

Minimum age

18 Years

Maximum age

75 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Need for any time critical interventions (e.g. reduction of dislocations or compound fractures) .

Digital injuries (pain from these should ideally be treated with digital block).

Pregnant and breastfeeding women (paracetamol and codeine are Category A drugs but Ibuprofen and oxycodone are Category C; with regard to lactation, paracetamol and ibuprofen are considered safe, but codeine and oxycodone are not recommended).

Asthma that may be Non-Steroidal Anti-inflammatory Drug (NSAID) sensitive.

Active peptic ulcer disease.

Known renal impairment.

Ethanol or recreational drug abuse or acute intoxication.

Use of any analgesic or sedating agent in the preceding 4 hours .

Regular use of analgesic agents for chronic pain.

Inability to take oral analgesics.

Known allergy or intolerance to paracetamol, to any opiate, or to any NSAID including Aspirin.

Patients not willing to comply with the recommendation not to drive, consume alcohol or operate machinery for at least 8 hours after being given the study drug combination.

Patients unable to understand the study explanation or unwilling to participate for whatever reason.

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)

The Triage Nurse in the emergency department will ask all patients with isolated limb injury for a 0-10 pain rating in the usual way. When the rating is greater than 3 and less than or equal to 7 and the patient appears otherwise eligible, the Triage Nurse will inform the SRO who will assess the patient for eligibility as soon as possible and will obtain informed consent where eligibility is confirmed.

Study recruitment officers will include Emergency Physicians, medical students, pharmacists and other trained doctors working in the ED. They will recruit the convenience sample of patients that meet the inclusion criteria and without exclusion criteria.

We will endeavor to flag potential participants using our electronic triage and patient tracking system in concert with the Triage Nurse. This will alert clinicians to potential subjects and also help us retrospectively determine numbers of potential subjects not approached for trial consideration given various constraints of the ED setting.

If the SRO, for whatever reason, believes that study recruitment will be delayed for more than fifteen minutes, then the SRO will tell the Triage Nurse that timely recruitment is not going to be possible and that nurse initiated analgesia should be instituted as per protocol.

On obtaining informed consent, the SRO/treating doctor will order the study medication on a standard hospital medication chart. The prescribing doctor will need to write on the "Once only medication" section (front of the drug chart labeled with the patients URN and name).
"Trial medication, study number XXX: paracetamol 500mg ii
ibuprofen 200mg ii
one of codeine 30mg ii / oxycodone 5mg ii / thiamine 100mg ii"
The nurses & others involved in the trial are then legally able to sign out the trial packs and/or administer the medication to the patient from this drug order.

Drug packs will be pre-packaged in the hospital pharmacy and numbered sequentially. Treatment arms will be randomised in blocks of 18 packs. Neither the Study recruitment officer nor the patient will know which drugs have been administered.

To ensure this style of prescribing is adhered to & uniform across sites, we will purchase a stamp with the template for the medication order on it. The SRO or ED nurse will obtain the labeled study drug container from the drug safe and the identically numbered Study Kit from the drug room. The container will be labelled 'study drug'. The container will be an opaque plastic container and the contents cannot be seen from the outside.

The SRO will complete the initial sections of the Case Report Form (CRF) and obtain the first (Time 0) VAS rating.

The patient will be given the study medication and a cup of water and will be asked to take the study medications without looking at the tablets and out of view of the SRO. The SRO will ensure the obtaining of the follow up VAS ratings at Time 0+15min, 0+30min, 0+45min, 0+60 min and 0+90min. The need for additional analgesia (‘rescue medication’) will be assessed at each time point. To assess the need for rescue analgesia, patients will be asked if their pain is much better, a little better, much the same, a little worse, or much worse, and their answer will be documented.

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

Block randomisation

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Phase

Phase 4

Type of endpoint/s

Efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

31/08/2010

Actual

1/10/2010

Date of last participant enrolment

Anticipated

31/10/2013

Actual

31/10/2013

Date of last data collection

Anticipated

Actual

Sample size

Target

216

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Recruitment postcode(s) [1]

3186

Recruitment postcode(s) [2]

3175

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Southern Health Emergency Research Group

Address [1]

Dept of Emergency Medicine
Monash Medical Centre
Clayton Rd
Clayton, 3168, Victoria

Country [1]

Australia

Primary sponsor type

Hospital

Name

Southern Health Emergency Research Group

Address

Dept of Emergency Medicine
Monash Medical Centre
Clayton Rd
Clayton, 3168, Victoria

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Southern Health Human Research and Ethics Committee

Ethics committee address [1]

Monash Medical Centre
Clayton Rd
Clayton, 3168, Victoria

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

15/05/2010

Approval date [1]

Ethics approval number [1]

Summary

Brief summary

Very little information exists on the effectiveness of oral pain-relieving medication administered acutely to adult patients presenting to the Emergency Department (ED) with moderate pain. As a result, the most effective combination of pain-relievers for acute pain is unknown. Studies in children in the emergency setting have suggested that a number of pain reliever combinations may be equally as effective for the treatment of moderate pain. Similar studies have not been replicated in adults.
Southern Health (SH) Emergency Medicine has an established guideline for the management of patients presenting to the Emergency Department with pain. The triage Nurse may administer one of a number of combinations of pain relieving medications provided certain clinical requirements are met. However, the guideline for pain relief when a patient has moderate pain (pain score >3 and <8), is not clear, suggesting the administration of a number of pain relief alternatives. These include; paracetamol with oxycodone and Ibuprofen, or alternatively Panadeine Forte-Registered Trademark (R) (paracetamol & codeine phosphate) with or without ibuprofen. It is not clear from past research whether or not one combination is superior. Additionally, the ease of nursing accessibility varies with oxycodone and Panadeine Forte(R) due to the different drug schedule of each pain reliever. Oxycodone is an S8 drug, requiring a higher degree of security and accountability to dispense. This has implications for nursing time to retrieve and give the drug to patients. Anecdotally, there is a perception by some emergency nursing staff that it may be easier or quicker to administer Panadeine Forte(R) compared to oxycodone. Some studies done in other settings suggest that oxycodone with paracetamol may be a more effective pain reliever for acute pain than Panadeine Forte(R), but data is conflicting and despite numerous systematic reviews of both pain relievers the differences may be small in patients with moderate pain. In the initial management of moderate pain at triage, the small benefit oxycodone+paracetamol confers over Panadeine Forte (R) may be offset by the added time it takes to deliver the former agent to the patient and the subsequent time of onset of pain relief.
Our study intends to compare three widely accepted combinations of analgesics for treatment of moderate pain in adults who present to the ED following acute limb injury. Firstly, paracetamol 1g with ibuprofen 400mg will be compared to 2) Codeine Phosphate 60 mg with paracetamol 1g and ibuprofen 400mg and, 3) Oxycodone (Endone (R)) 10 mg with paracetamol 1g and ibuprofen 400mg. All of these drugs are currently included in some combination in the current Southern Health Emergency Medicine nurse-initiated pain guideline for management of moderate pain. 
The study will be carried out in all three Southern Health EDs. Subjects will be given one of three randomly assigned and unknown combinations of the drugs. Their pain scores will be determined at regular intervals for 90 minutes. There will be regular monitoring for side effects and for the need for additional painkillers. We aim to recruit 216 subjects. Equal relief of pain with all the regimens may improve delivery of pain relief in the ED by reducing the need to access S8 medications in moderate pain, thus reducing time to delivery of effective analgesia. If the oxycodone arm is found to provide superior analgesia the current guideline could be amended to simplify the currently recommended treatment options. Alternatively if it is found the arm without opioid analgesia is equivalent  the routine use of codeine and oxycodone for moderate pain will be reviewed.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Alastair Meyer

Address

Department of Emergency Medicine Casey Hospital 52 Kangan Drive Berwick, 3806, Victoria

Country

Australia

Phone

+61 3 8768 1200

Fax

alastair.meyer@southernhealth.org

Contact person for public queries

Name

Dr Alastair Meyer

Address

Department of Emergency Medicine
Casey Hospital
52 Kangan Drive
Berwick, 3806, Victoria

Country

Australia

Phone

+61 3 8768 1200

Fax

alastair.meyer@southernhealth.org

Contact person for scientific queries

Name

Andis Graudins

Address

Department of Emergency Medicine
Monash Medical Centre
Clayton Rd
Clayton, 3168, Victoria

Country

Australia

Phone

+61 3 9594 3195

Fax

andis.graudins@monash.edu

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

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	A randomised controlled trial of paracetamol and ibuprofen with or without codeine or oxycodone as initial analgesia for adults with moderate pain from limb injury.	2016	https://dx.doi.org/10.1111/1742-6723.12672

N.B. These documents automatically identified may not have been verified by the study sponsor.

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