Morphine And BrEathLessness trial (MABEL)

Phase 1

Conditions: Chronic breathlessness due to cardiac, respiratory disease or cancer.
MedDRA version: 20.0Level: PTClassification code 10007554Term: Cardiac failureSystem Organ Class: 10007541 - Cardiac disorders
MedDRA version: 21.1Level: LLTClassification code 10009026Term: Chronic obstructive airways diseaseSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
MedDRA version: 21.1Level: PTClassification code 10022611Term: Interstitial lung diseaseSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
MedDRA version: 21.0Level: LLTClassification code 10048683Term: Advanced cancerSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Registration Number: EUCTR2019-002479-33-GB

Lead Sponsor: Hull University Teaching Hospitals NHS Trust

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 158

Inclusion Criteria

CTIMP trial
Patients:
1.Ambulant people with chronic breathlessness due to cardiac, respiratory disease or cancer. Chronic breathlessness is defined as those with persistent disabling breathlessness despite optimum treatment of their underlying disease in the opinion of the identified clinician.
2.Breathlessness severity.
Medical Research Council (mMRC) breathlessness scale grade 3 or 4 (i.e. stops for breath after walking about 100 yards or after a few minutes on level ground, or is too breathless to leave the house or is breathless when dressing). A pooled data study shows that people with worse baseline breathlessness are more likely to respond to opoids. A phase 3 trial in people with COPD showed that those with mMRC grade 3 or 4 were more likely to respond to opioids. This approach also concurs with clinical recommendations.
3.Male or female aged = 18 years old
4.Management of the underlying condition unchanged for the previous 7 days. This, and criterion 5, excludes the very unstable patient who is unlikely to complete the 56 day RCT phase.
5.Australia-modified Karnofsky Performance Scale (AKPS) =40. This, with criterion 4, is to identify patients most likely to complete the 2 months RCT phase.
6.eGFR of 25 mls/min/1.732 or more, unless the primary diagnosis is heart failure (=30 mls/min/1.732) within 21 days of consent. Renal clearance of eGFR =25 mls/min/1.732 is adequate for the study doses of morphine, however, in heart failure patients are more likely to have fluctuations in renal function for which the higher level will allow.
7.If female and of child-bearing potential, must agree to use adequate contraception when taking IMP and for 7 days following cessation****
8.Able to complete questionnaires and trial assessments
9.Able to provide written informed consent

Carers:
1. Family or friend providing care for a patient participant (consented) as identified by the patient participant
2. Male or female = 18 years old
3. Able to complete study carer assessments
4. Able to provide written informed consent

Implementation study
Clinicians:
Prescribers (or those supporting prescribers) at trial sites attending a site clinical training session

Patients and carers:
CTIMP participants and their carers where the participant has completed at least 14 days of the trial
Those willing to participate in a face-to-face or telephone interview and able to provide informed written consent

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 110
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 48

Exclusion Criteria

CTIMP trial
Patient participants
1.Are unable to provide informed consent.
2.Are unable to complete baseline study questionnaires even with the assistance of the study nurse
3.Have co-existing malignant disease only if this would affect the study in the investigators’ opinion.
4.Have used opioid medications >5mg morphine-equivalents daily for > 7 out of last 14 days.
5.Have known true morphine or docusate allergies or hypersensitivity to any of the tablet constituents as assessed by a clinician.
6.Have known central hypoventilation syndrome (e.g. Ondine’s curse post stroke)
7.Have been involved in another medicinal trial (CTIMP) within the past 28 days
8.Are pregnant or lactating.
9.Have respiratory depression, head injury, paralytic ileus, 'acute abdomen', acute hepatic disease,
10.Have concurrent administration of monoamine oxidase inhibitors or are within 14 days of discontinuation of their use.
11.Are within the first 24 hours post-operatively
12. Are taking more than 20mg diazapam equivalents per day or are not able or willing to safely reduce dose to less or the same as 20mg / day for the duration of the study.

Carer participants
1. Does not meet inclusion criteria

Implementation study:

Clinicians:
Clinicians not working at a trial site

Patients and carers:
Participants with insufficient written or conversational English to be able to provide informed consent or take part in an interview and adequate translation facilities are unavailable

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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