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Trial registered on ANZCTR


Registration number
ACTRN12613000709741
Ethics application status
Approved
Date submitted
21/06/2013
Date registered
28/06/2013
Date last updated
28/06/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
Patient-controlled analgesia with methoxyflurane (Penthrox inhaler) versus conventional endoscopist-provided sedation for colonoscopy: a randomized multi-centre trial
Scientific title
For Patients undergoing colonoscopy, will patient-controlled analgesia with methoxyflurane (Penthrox inhaler) versus conventional endoscopist-provided sedation for colonoscopy be as effective and safe in providing adequate analgesia.
Secondary ID [1] 282710 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alternative Pain relief in patients undergoing colonoscopy 289424 0
Condition category
Condition code
Anaesthesiology 289757 289757 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Those randomised to the methoxyflurane arm will be given extra instructions on the use of the Penthrox inhaler. They will then be asked to inhale the methoxyflurane for approximately 2 minutes as a pre-medication from one, 3mL dose in a Penthrox inhaler. Since methoxyflurane has a sweet tasting smell, patients will be advised to breathe in a stepwise fashion (from shallow to deep) over that 2 minute period. Once the colonoscopy has commenced, patients will be encouraged to take an adequate inhalation of methoxyflurane to provide sufficient analgesia. Patients are then allowed to self administer as much methoxyflurane as they feel they require within the safety limit as recommended by the manufacturer (6mL /day). Furthermore, they will be instructed to self administer further doses of methoxyflurane by the endoscopist if the endoscopist anticipate potential loops which may cause discomfort.
Intervention code [1] 287371 0
Treatment: Drugs
Comparator / control treatment
Those in the control group will receive an initial bolus of fentanyl and midazolam before the procedure based on their age. A further bolus of these medications will be given during the procedure at the discretions of the endoscopist: 1-2mg midazolam every 10-15 mins, and 25-50mcg fentanyl every 10-15 mins (AMH 2009).
Recommended initial dosage of midazolam and fentanyl for colonoscopy stratify by the patient’s age (ref_AMH 2009) is as follows:

Age <60 dose: Midazolam =2.5mg and Fentanyl=100mcg
Age equal to or >60 dose: Midazolam =1.5mg and Fentanyl=50mcg
Control group
Active

Outcomes
Primary outcome [1] 289840 0
Time from end of procedure to discharge.
Timepoint [1] 289840 0
Time of discharge is defined as the time which the caring nurses and physician deem “medically safe” for the patients to leave the Endoscopic Unit. Any delay due to transport need or other unrelated medical issue will not be included. These timing data will be prospectively documented.
Primary outcome [2] 289841 0
Pain and anxiety scores during colonoscopy as measured by a Visual Analogue Scale (VAS) and the State Trait Anxiety Inventory (STAI-Y-1).
Timepoint [2] 289841 0
After the procedure and adequate recovery time (1 hr minimum as per standard GIU protocols) and also 24 hours after the procedure (asked over the phone)
Secondary outcome [1] 303359 0
Safety and occurrence of adverse events

Adverse events for Penthrox:
Infrequent (<10%): nausea, vomiting, coughing, drowsiness, dizziness, fever, frequent urination, and headache.
Rare (<1%): minor disturbances to your liver and kidney function, over-sedation, or slow heart rate.

Adverse events for Midazolam:
Infrequent (<10%): low blood pressure, hiccup, coughing, rash, headache, nausea and vomiting,
Rare (<1%): confusion, restlessness, and over-sedation.

Adverse events for Fentanyl:
Infrequent (<10%): nausea and vomiting, drowsiness, low blood pressure, itch, dry mouth, headache
Rare (<1%): confusion and over-sedation.
Timepoint [1] 303359 0
The research nurse will contact the patients 48h and 30days after the colonoscopy to check for the occurrence of any adverse events.
Secondary outcome [2] 303360 0
Polyp detection rate
Timepoint [2] 303360 0
Documented during coloscopy
Secondary outcome [3] 303361 0
Rate of completing colonoscopy
Timepoint [3] 303361 0
Documented after each colonoscopy
Secondary outcome [4] 303362 0
Rate of procedure complications i.e. perforation, internal bleeding.
Timepoint [4] 303362 0
documented during colonoscopy
Secondary outcome [5] 303363 0
Colonoscopy procedural time
Timepoint [5] 303363 0
The timepoint when the procedure is complete and the scope has been removed
Secondary outcome [6] 303364 0
Use of rescue medication prior to completion of procedure
Timepoint [6] 303364 0
During colonoscopy
Secondary outcome [7] 303365 0
Patient’s recollection of the procedure
Timepoint [7] 303365 0
After the procedure and adequate recovery time (1 hr minimum as per standard GIU protocols
Secondary outcome [8] 303366 0
Participant global medication performance assessment measured using a 5 point Likert Scale
Timepoint [8] 303366 0
After the procedure and adequate recovery time (1 hr minimum as per standard GIU protocols)
Secondary outcome [9] 303367 0
Research nurse global medication performance assessment measured using a 5 point Likert Scale
Timepoint [9] 303367 0
After the procedure and adequate recovery time (1 hr minimum as per standard GIU protocols)
Secondary outcome [10] 303368 0
Endoscopist global medication performance assessment measured using a 5 point Likert Scale
Timepoint [10] 303368 0
After the procedure and adequate recovery time (1 hr minimum as per standard GIU protocols)

Eligibility
Key inclusion criteria
Able to give informed consent
Adequate understanding of use of the Penthrox inhaler
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
History of significant alcohol (>40gms/d for males, 20gms/d for females) or narcotic use.
Previous history of significant cardiac or respiratory illnesses (ie. ischaemic heart disease, chronic obstructive pulmonary disease).
Significantly underweight (<45kg)
Significant smoking history of more than 20 packs / year.
Previous history of gastrointestinal surgery (likely to increase difficulty of colonoscopy)
Renal impairment
Diabetes Mellitus
Previous possible allergy to the medication by the patient or a relative
Hypersensitivity to fluorinated agents
Previous head injury
Difficulty in following instructions (including language barrier)
Patients taking any potential nephrotoxic drugs (e.g. aminoglycosides)
Personal or a family history of malignant hyperthermia.
Patients without English literacy

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 study will be conducted as a randomised controlled multi-centre trial in adult participants requiring analgesia associated with a planned colonoscopy. Patients will be recruited for this study from either an outpatient setting or through the Endoscopic suite. Together with the appointment form for the colonoscopy procedure, the study Information Sheet will be sent to suitable patients to invite them to participate in the study. This should allow enough time for the patients to read and understand the study prior to the procedure time. These patients will then be approached in the Endoscopic Unit prior to colonoscopy regarding participation in the study. If they are agreeable to the study, they will be randomised to receive either methoxyflurane or conventional sedation (midazolam and fentanyl) in anticipation of incident pain associated with colonoscopy, in 1:1 ratio.
The patients are assigned a patient number when they are recruited into the study. On the day of their procedure, these numbers are then plugged into the random number generator of the computer program Graphpad Prism which randomly assigns a group allocation to each number. In this way, allocation is concealed as the person recruiting the subjects has no way of knowing which group the subject will be allocated to.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The method used to generate the sequence in which the subjects will be randomised will be done using the computer program Graphpad Prisms random number generator, which is seeded with the time of day, so it works differently each time you use it. Each day, the numbers of the subjects who have agreed to undergo the trial is plugged into the program, then the program first assigns each numbered subject to a group nonrandomly. Then the assignment of each subject is swapped with the group assignment of a randomly chosen subject. This process is repeated twice to ensure true randomness.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Sample size calculations have been made based upon the results of the pilot study, published in JGH 2008, A227. Using the endpoint of mean “patient’s discomfort score” and related standard deviation, power calculation with a two-sided significance level of 0.05, power of 90% and assuming that a difference of 1.0 in mean discomfort score is clinically important, the trial will need to recruit a minimum of 112 participants per treatment arm. Taken into account of the 30% drop-off rate from enrolment, the FINAL required sample size would be 299, which is an odd number for 1:1 randomization. Therefore, the minimum sample size of 300 was chosen.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/01/2011
Actual
21/01/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
300
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 1148 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 1149 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [3] 1152 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment postcode(s) [1] 6995 0
5000 - Adelaide
Recruitment postcode(s) [2] 6998 0
5011 - Woodville
Recruitment postcode(s) [3] 6999 0
5112 - Elizabeth Vale

Funding & Sponsors
Funding source category [1] 287490 0
Hospital
Name [1] 287490 0
Department of Gastroenterology & Hepatology, Royal Adelaide Hospital
Country [1] 287490 0
Australia
Funding source category [2] 287491 0
Commercial sector/Industry
Name [2] 287491 0
Medical Developments International Ltd
Country [2] 287491 0
Australia
Primary sponsor type
Individual
Name
Dr. Nam Q Nguyen
Address
Department of Gastroenterology & Hepatology
Q7 Level 7 North Wing
Royal Adelaide Hospital
North Terrace
Adelaide, SA, 5000
Country
Australia
Secondary sponsor category [1] 286229 0
Individual
Name [1] 286229 0
Dr Biju George
Address [1] 286229 0
Department of Gastroenterology and Hepatology
Lyell McEwin Hospital
Haydown Road
Elizabeth Vale
SA, 5112
Australia
Country [1] 286229 0
Australia
Secondary sponsor category [2] 286230 0
Individual
Name [2] 286230 0
Prof Ian Roberts-Thomson
Address [2] 286230 0
Gastroenterology and Hepatology Unit, 4B
The Queen Elizabeth Hospital
28 Woodville Road
Woodville South SA 5011
Country [2] 286230 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289465 0
Royal Adelaide Hospital Research Ethics Comittee
Ethics committee address [1] 289465 0
Ethics committee country [1] 289465 0
Australia
Date submitted for ethics approval [1] 289465 0
Approval date [1] 289465 0
27/07/2010
Ethics approval number [1] 289465 0
100721

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 40934 0
Dr Nam Q Nguyen
Address 40934 0
Department of Gastroenterology & Hepatology
Q7 Level 7 North Wing
Royal Adelaide Hospital
North Terrace
Adelaide, SA, 5000
Country 40934 0
Australia
Phone 40934 0
+61 422 113 598
Fax 40934 0
Email 40934 0
quoc.nguyen@health.sa.gov.au
Contact person for public queries
Name 40935 0
Nam Q Nguyen
Address 40935 0
Department of Gastroenterology & Hepatology
Q7 Level 7 North Wing
Royal Adelaide Hospital
North Terrace
Adelaide, SA, 5000
Country 40935 0
Australia
Phone 40935 0
+61 422 113 598
Fax 40935 0
Email 40935 0
quoc.nguyen@health.sa.gov.au
Contact person for scientific queries
Name 40936 0
Nam Q Nguyen
Address 40936 0
Department of Gastroenterology & Hepatology
Q7 Level 7 North Wing
Royal Adelaide Hospital
North Terrace
Adelaide, SA, 5000
Country 40936 0
Australia
Phone 40936 0
+61 422 113 598
Fax 40936 0
Email 40936 0
quoc.nguyen@health.sa.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

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.