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Trial registered on ANZCTR


Registration number
ACTRN12611000711910
Ethics application status
Approved
Date submitted
22/04/2011
Date registered
11/07/2011
Date last updated
15/09/2020
Date data sharing statement initially provided
27/11/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Opioids for breathlessness in people with mesothelioma or asbestosis or other causes of interstitial lung disease.
Scientific title
A randomised, placebo-controlled, double-blind, cross-over study of the efficacy of sustained-release low dose morphine in the subjective sensation of dyspnoea as a result of maximally treated mesothelioma or asbestosis or other causes of interstitial lung disease in opioid naive participants.
Secondary ID [1] 259904 0
NIL
Secondary ID [2] 284344 0
nil known
Universal Trial Number (UTN)
Trial acronym
Opioids for dyspnoea in people with Mesothelioma or Interstitial Lung Disease .(MILD)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dyspnoea in opioid naive participants with mesothelioma or asbestosis or other causes of interstitial lung disease. 265506 0
Condition category
Condition code
Respiratory 265679 265679 0 0
Other respiratory disorders / diseases
Cancer 268170 268170 0 0
Lung - Mesothelioma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
One capsule of sustained- release Morphine 20mg taken orally, daily for 7 days, 1-2 tablets of Coloxyl and Senna taken orally, daily for the same 7 days, then a washout period of one week before crossing over to the placebo treatment .
Tablets contain Docusate Sodium 50mg total sennosides (calculated as sennosideB) 8mg
Intervention code [1] 264327 0
Treatment: Drugs
Comparator / control treatment
One capsule of sustained-release Morphine 20mg placebo taken orally, daily for 7 days.(This medication will be encased in an opaque capsule to ensure the study medication and placebo look identical).This placebo capsule will contain granulated Microcrystalline cellulose. Also taken will be 1-2 tablets of Coloxyl and Senna placebo taken orally, daily for 7 days.( this placebo formulation will be lactose, starch maize, gelatin, magnesium stearate, propyl hydroxybenzoate, opadry brown and carnauba wax and will have the same outward appearance as the intervention tablets.
Control group
Placebo

Outcomes
Primary outcome [1] 266467 0
The relief of breathlessness by the mean of the Dyspnoea Visual Analogue(VAS) scores. This will be calculated separately for morning (am) and evening (pm) scores. The unpleasantness of breathlessness will also be assessed.
Timepoint [1] 266467 0
On days 5,6 and 7, and days 19,20, and 21.
Secondary outcome [1] 273827 0
Differences in the frequency and severity of adverse effects between the two arms.The participant will be visited at home weekly and phoned weekly at times convenient to the patient, visits will last approximately 30-40 minutes. their blood pressure, heart rate and respiratory rate will be measured, their blood oxygen saturation by means of a pulse oximeter and their end tidal cardon dioxide by means of an end tidal carbon dioxide monitor.
Using the Anticipated Adverse Event Assessment frequent side effects of morphine sulphate will be monitored and categorised according to the National Cancer Institute Common Toxicity Criteria for Adverse Events.This will be assessed at both the home and phone contacts.
Adverse events will also be monitored by asking the patient if they have "any other problems" and how they rate the effectiveness of breathlessness control, both assessed twice weekly.They are asked to fill out the Chronic Respiratiory Questionnaire - Dyspnoea Subscale (Mcmaster University) weekly.
Timepoint [1] 273827 0
Days 4,7,14,18,21.
Secondary outcome [2] 273828 0
Changes in respiratory rate, pulse oximetry and end-tidal carbon dioxide.
A study nurse will visit the patient at home, at a time convenient to the patient to measure the respiratory rate and will use a pulse oximeter and an end tidal carbon dioxide monitor (all non invasive procedures).
Timepoint [2] 273828 0
Baseline,Day 7, second baseline (Day 14) and day 21.
Secondary outcome [3] 273829 0
Profile of the descriptive type(s) of the subjective sensation of dyspnoea that are more likely to be associated with mesothelioma, asbestosis or interstitial lung disease.
Participant will keep a diary for a maximum of 23 days, anticipated to take 5-10 minutes daily to fill out. They will be asked to indicate twice daily,the intensity of dyspnoea now on a modified Borg scale, the intensity and separately the unpleasantness of dyspnoea now, on a Visual Analogue Scale (VAS) and the intensity and unpleasantness of breathlessness on a four point catagorical score. To indicate once daily, their average breathlessness, worst breathlessness and best breathlessness in in the last 24 hours, each utilising a VAS scale and their exercise tolerance using the Medical Research Council of Great Britain Scale for Dyspnoea.
They will also be asked to indicate twice in their diary,at the end of each arm, (active and control) the level of dyspnoea control and the overall level of dyspnoea in the last 7 days and the level of satisfaction with medications received in the last 7 days.
(While measurements and analysis will be based upon the data from the last 3 days of each arm participants are also asked to provide responses once or twice daily to make sure they are comfortable with the pattern of participation prior to responding on the key census days).
Timepoint [3] 273829 0
Days 5, 6, 7 and 19, 20, 21.
Secondary outcome [4] 273830 0
Define any changes in quality of life generated by either arm of the study by using the McMaster Chronic Respiratory Questionnaire - Dyspnoea Sub-scale. This will be filled by the patient 4 times at study nurse home visits.( visits will lasting about 30-40 minutes)
Timepoint [4] 273830 0
Baseline, day 7, second baseline (day 14) and Day 22
Secondary outcome [5] 273831 0
Profile of the clinical characteristics of people who derive the greatest benefit from sustained release morphine in either clinical setting ( mesothelioma/asbestosis or interstitial lung disease).
This will be assessed from the subjective responses to questions relating to the sensation of breathlessness in the patient diary on the last 3 days of each arm of the study.
Timepoint [5] 273831 0
Timepoint: Baseline and days 5, 6,7,19,20,and 21
Secondary outcome [6] 273832 0
Determine whether there is blinded preference for the net clinical benefit of one arm in the study. This will be assessed from questions asked of the patient in the daily diary, only asked at the end of both the active and contol arms.These questions will relate to the effectiveness of breathlessness control, the overall level of breathlessness, and their level of satisfaction with the medications received only in the last 3 days of each arm of the study.
Timepoint [6] 273832 0
Days 5,6,7,19,20.and 21.

Eligibility
Key inclusion criteria
English speaking. Participants over the age of 18.Dyspnoea (3 or greater on the Medical Research Council scale) secondary to mesothelioma,asbestosis or any other cause of restrictive type pattern of interstitial lung disease. Renal function - calculated creatinine clearance >10mmol/l. Haemoglobin > 10 g/dl, or treating clinician has reviewed the haemoglobin result and confirmed that particpant does not need a blood transfusion. On stable oxygen - no changes to prescription in the last 3 days. On stable medications – no changes to prescription medications in the last 3 days. Able to complete participant diary.Willing and able to give informed consent.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Taking regular opioid medications.True adverse reaction(s) to morphine previously. Known hypersensitivity to any of the morphine sulphate capsule components. History of central hypoventilation syndrome.
Use of monoamine oxidase inhibitor(s) (MAOIs) in the last 2 weeks or proposed use during the study. Australian Karnofsky Modified Performance Status (modified AKPS) < 50. Acutely confused (Nursing Delirium Assessment Scale score > 0 at baseline).Cognitive impairment (Mini-Mental State Examination < 24 at baseline). Uncontrolled nausea or vomiting.
Gastrointestinal obstruction or documented peritoneal mesothelioma. Pregnancy, risk of pregnancy or breast feeding mothers.
Past history of significant illicit opioid misuse.

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)
Participants ( outpatients and potentially inpatients) will be recruited from respiratory outpatients clinics at several centres around Australia and screened for eigibility for the study. Allocation involves contacting the holder of the allocation schedule who will be 'off-site".
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be block randomised at each site in a double-blind fashion bya clinical pharmacist at a central site for each study.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Crossover
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Suspended
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)
NSW,SA,VIC
Recruitment hospital [1] 12560 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [2] 12561 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [3] 17538 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 24939 0
3050 - Parkville
Recruitment postcode(s) [2] 24940 0
5042 - Bedford Park
Recruitment postcode(s) [3] 31271 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 264812 0
Government body
Name [1] 264812 0
Workers' Compensation Dust Diseases Board of NSW
Address [1] 264812 0
Level 2, 82 Elizabeth St

Sydney NSW 2000
Country [1] 264812 0
Australia
Primary sponsor type
University
Name
Flinders University - Department of Palliative and Support Services
Address
Flinders Drive
Bedford Park
SA 5042
Country
Australia
Secondary sponsor category [1] 263920 0
None
Name [1] 263920 0
Address [1] 263920 0
Country [1] 263920 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 266784 0
Southern Adelaide Flinders Clinical Human Research Ethics Committee. (SAFC HREC)
Ethics committee address [1] 266784 0
Flinders Medical Centre
Flinders Drive
Bedford Park
South Australia SA 5042
Ethics committee country [1] 266784 0
Australia
Date submitted for ethics approval [1] 266784 0
Approval date [1] 266784 0
09/11/2010
Ethics approval number [1] 266784 0
269_10
Ethics committee name [2] 302041 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [2] 302041 0
The Royal Melbourne Hospital
300 Gratton St
Parkville VIC 3050
Ethics committee country [2] 302041 0
Australia
Date submitted for ethics approval [2] 302041 0
26/02/2020
Approval date [2] 302041 0
25/05/2020
Ethics approval number [2] 302041 0
HREC/46442/MH-2020

Summary
Brief summary
This study aims to determine whether morphine reduces the feeling of breathlessness in patients with mesothelioma, asbestosis or interstitial lung disease.

Who is it for?
you can join this study if you are 18 years or more, and suffer from a feeling of breathlessness (dyspnoea) as a result of maximally treated mesothelioma, asbestosis, or interstitial lung disease. You must be able to speak English and should not be taking regular opioid medication (painkillers).

Trial details
Participants in this trial will be randomly (by chance) assigned to receive either 20mg sustained-release morphine (by oral capsule) together with a laxitive Coloxyl and Senna, or placebo (sham) tablets for one week. They will receive no medication for the second week and will then receive the alternate treatment ( morphine or placebo) for the third week. Participants will not know when they are taking the active drug or placebo.

Participants will be asked to complete questionnaires and keep a diary over the 3 weeks of the trial to determine their response to treatment. They will also be phoned and visited at home by a nurse to monitor any side effects of treatment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32429 0
Prof David Currow
Address 32429 0
Department of Palliative and Supportive Services Flinders University Flinders Drive, Bedford Park, SA 5042
Country 32429 0
Australia
Phone 32429 0
+61 414190084
Fax 32429 0
None
Email 32429 0
david.currow@flinders.edu.au
Contact person for public queries
Name 15676 0
Prof Prof David Currow
Address 15676 0
Department of Palliative and Supportive Services Flinders University Flinders Drive, Bedford Park, SA 5042
Country 15676 0
Australia
Phone 15676 0
+61 414190084
Fax 15676 0
None
Email 15676 0
david.currow@flinders.edu.au
Contact person for scientific queries
Name 6604 0
Prof Prof David Currow
Address 6604 0
Department of Palliative and Supportive Services Flinders University Flinders Drive, Bedford Park, SA 5042
Country 6604 0
Australia
Phone 6604 0
+61 414190084
Fax 6604 0
None
Email 6604 0
david.currow@flinders.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Not described within original protocol
What supporting documents are/will be available?
No other documents available
Summary results
No Results