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Trial registered on ANZCTR

Registration number
Ethics application status
Submitted, not yet approved
Date submitted
Date registered
Date last updated
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy of low-dose methadone as an antitussive for patients with malignancy. A pilot study.
Scientific title
Efficacy of low-dose methadone as an antitussive for patients with malignancy. A pilot study.
Secondary ID [1] 289528 0
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
cough in malignancy 299235 0
Condition category
Condition code
Cancer 299245 299245 0 0
Any cancer
Respiratory 299259 299259 0 0
Other respiratory disorders / diseases

Study type
Description of intervention(s) / exposure
Patients will be randomised 1:1 to receive either methadone 5mg twice daily (oral tablet) or placebo twice daily (oral tablet) from Day 1 to Day 3, followed by a single day washout period (Day 4), and then swapping to the alternative (placebo or methadone) for three days (Day 5 to Day 7). Adherence monitored by empty drug packet return.
Intervention code [1] 295118 0
Treatment: Drugs
Comparator / control treatment
Microcellulose (tablet)
Control group

Primary outcome [1] 298728 0
The proportion of patients with a clinically significant reduction in cough as evidenced by a drop in mean Leister Cough Quenstionnaire (LCQ) of 1.3 or in mean Cough Visual Analogue Scale (VAS) by 8 mm
Timepoint [1] 298728 0
Baseline, End of Day 3, Start of Day 5, end of Day 7
Primary outcome [2] 299017 0
Proportion of participants with an improvement in Quality of life by drop on mean leister Cough Quenstionairre and Cough Visual analgoue scale
Timepoint [2] 299017 0
Baseline, End Day 3, Start Day 5, end Day 7
Secondary outcome [1] 325079 0
Safety of adding low dose methadone to patients' existing medications as an antitussive. Physical examination and documentation of adverse events as per CTCAE v3.
Risks of Methadone
The known risks of this study which are principally related to methadone use are:

Common (greater than 1 in 100 patients)
Dry mouth
Respiratory depression (Hypoventilation)
Psychiatric effects including euphoria, hypomania, and behaviour disturbances

Infrequent (between 1 in 100 and 1 in 1000 patients):
Inflammation of the tongue (Glossitis)
Loss of strength or weakness
Low blood pressure (Hypotension)
Low body temperature (Hypothermia)
Swelling (Oedema)
Spasm of the renal tract

Rare (less than 1 in 1000 patients):
Abdominal pain
Lack of appetite (Anorexia)
Biliary tract spasm
Mood Changes
Heightened state of restlessness (Dysphoria)
Changes to the electrical and muscular functions of the heart.
Enlargement of Breasts in Men (Gynaecomastia) - only with prolonged use
Timepoint [1] 325079 0
Day 7 following first dose of first study treatment
Secondary outcome [2] 325080 0
Explore patients' current knowledge level and attitudes to methadone as a palliative medication and compare that with morphine and other opiods. Patients will be given a single structured survey to complete at the time of recruitment with regards to their attitudes to opioids. This will be a survey custom designed for this study.
Timepoint [2] 325080 0
Day 7 following first dose of first study treatment
Secondary outcome [3] 325081 0
Examine patients' methadone plasma levels at end of treatment and determine if plasma level correlates with antitussive effect.Correlation between plasma methadone and antitussive effect as assessed by the LCQ and VAS.
Timepoint [3] 325081 0
A blood sample will be collected at Day 7 following first dose of first study treatment

Key inclusion criteria
Screening ESAS (Edmonton Symptom Assessment Score administered as per standard Monash Supportive and Palliative Care Unit practice) of cough score of four or more
Able to give informed consent
English speaking
Malignancy requiring palliative care
Minimum age
18 Years
Maximum age
No limit
Both males and females
Can healthy volunteers participate?
Key exclusion criteria
Currently receiving systemic anticancer treatment including:
Any systemic cytotoxic chemotherapy or targeted therapy
Any radiotherapy to thorax within the past month
Known allergy or sensitivity to opioids
Any increase or commencement of corticosteroids within the last three days

Study design
Purpose of the study
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Other design features
Phase 4
Type of endpoint(s)
Statistical methods / analysis
Sample size was calculated by using previous reports of LCSS scores in patients with chronic cough. The predicted standard deviation of the LCCS was 2.8 points. Previous studies have shown that a -1.3 point difference in pre- and post-treatment LCCS scores to be clinically significant. To provide 80% power to detect this 1.3 difference (if 10% dropout rate, two-sided testing and a required a value of <0.05 is assumed), 40 patients will be required.
Visual Analogue Scale of 0-100mm. The predicted standard deviation being 16mm. 40 participants would provide 80% power to detect a clinically significant difference of 8mm in the scale with an a of 0.05 allowing for a 10% dropout rate.

Recruitment status
Not yet recruiting
Date of first participant enrolment
Date of last participant enrolment
Date of last data collection
Sample size
Accrual to date
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 13443 0
3168 - Clayton
Recruitment postcode(s) [2] 13444 0
3165 - Bentleigh East
Recruitment postcode(s) [3] 13445 0
3175 - Dandenong
Recruitment postcode(s) [4] 13446 0
3806 - Berwick

Funding & Sponsors
Funding source category [1] 293905 0
Name [1] 293905 0
Bethlehem Griffiths Research Foundation
Address [1] 293905 0
476 Kooyong Rd, Caulfield South VIC 3162
Country [1] 293905 0
Primary sponsor type
Government body
Monash Health
246 Clayton Rd Clayton VIC 3168
Secondary sponsor category [1] 292729 0
Name [1] 292729 0
Address [1] 292729 0
Country [1] 292729 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 295321 0
Monash Health Human Research Ethics Committee
Ethics committee address [1] 295321 0
246 Clayton Rd Clayton VIC 3168
Ethics committee country [1] 295321 0
Date submitted for ethics approval [1] 295321 0
Approval date [1] 295321 0
Ethics approval number [1] 295321 0

Brief summary
The primary purpose of this trial is to evaluate the safety and efficacy of methadone for the treatment of chronic cough in cancer patients in palliative care.

Who is it for?
You may be eligible to participate in this trial if you are aged 18 or over, suffer from chronic cough following diagnosis of cancer, and are currently in palliative care.

Study details
Participants enrolled in this trial will receive 3 days treatment with methadone and 3 days treatment with a placebo (sham) treatment with a no treatment day in between (total of 7 days).. The order in which these are given is randomly allocated (by chance). Each treatment period involves taking two tablets per day, and there will be a break period of 1 day between each of the two treatments. Participants will be asked to complete a number of questionnaires relating to the severity of their cough, and provide a blood sample at the end of each 3 day treatment period.

It is hoped that this trial will provide information on whether methadone is a safe and effective treatment for cough in cancer patients, which may be used to inform a larger clinical trial in the future.
Trial website
Trial related presentations / publications
Public notes

Principal investigator
Name 66878 0
A/Prof Michael Franco
Address 66878 0
Monash Health
865 Centre Rd East Bentleigh VIC 3165
Country 66878 0
Phone 66878 0
+61 3 9928 8120
Fax 66878 0
+613 9928 8341
Email 66878 0
Contact person for public queries
Name 66879 0
A/Prof Michael Franco
Address 66879 0
Monash Health
865 Centre Rd East Bentleigh VIC 3165
Country 66879 0
Phone 66879 0
+61 3 9928 8120
Fax 66879 0
+613 9928 8341
Email 66879 0
Contact person for scientific queries
Name 66880 0
A/Prof Michael Franco
Address 66880 0
Monash Health
865 Centre Rd East Bentleigh VIC 3165
Country 66880 0
Phone 66880 0
+61 3 9928 8120
Fax 66880 0
+613 9928 8341
Email 66880 0

No information has been provided regarding IPD availability
Summary results
No Results