Morphine for Dyspnea in Pulmonary Fibrosis

Study Overview
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Brief Summary
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Determination of the effectiveness of nebulized morphine in the treatment of dyspnea in patients with advanced idiopathic pulmonary fibrosis

Official Title
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Determining the Effectiveness of Nebulized Morphine in Treating Dyspnea in Advanced Idiopathic Pulmonary Fibrosis

Conditions
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Idiopathic Pulmonary Fibrosis (IPF)

Intervention / Treatment
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* Drug: Morphine hydrochloride
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: IPF diagnosis in accordance with guidelines Period of stable disease Dyspnea rated 3 to 4 in mMRC scale Current non-smoker Other potential causes of breathlessness such as kidney or heart failure optimally treated in the opinion of the principal investigator Able to complete questionnaires and trial assessments Ability to give informed consent If female, must be: postmenopausal (no menses for 12 months without an alternative medical cause) sterile using acceptable contraception and agree to exclude pregnancy with pregnancy test in the beginning of the hospitalization Exclusion Criteria: - other coexisting severe chronic lung diseases absolute contraindications to six-minute-walking-test according to Polish Respiratory Society guidelines: < 7-10 days since coronary interventions due to STEMI < 24 h since planned coronary intervention myocarditis/pericarditis symptomatic rhythm and conduction abnormalities acute deep vein thrombosis, pulmonary embolism, pulmonary infarction decompensated heart failure acute infection and other diseases which can significantly impact the test result (eg. severe anemia, acute kidney or liver failure, hypo- or hyperthyroidism, etc) - contraindications to morphine hydrochloride: previous history of respiratory depression after opioid administration previous history of allergic reactions to opioids severe ventilation impairment due to e.g. asthmatic state, airway foreign body severe kidney or liver failure increased intracranial pressure head injury cerebral edema coma seizure disorders acute alcohol poisoning acute abdomen acute diarrhea caused by infection or food poisoning; patients at risk of paralytic ileus; biliary colic; phaeochromocytoma; simultaneous MAO inhibitor treatment and immediate 2-week period following its discontinuation - ongoing opioid treatment for any indication

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The study is a randomized, double-blind, placebo-controlled analysis conducted with crossover arms. The study consists of two treatment periods lasting a total of 5 days: 2 days of nebulization with 0.9% NaCl and 2 days of nebulization with 2.0% morphine hydrochloride solution separated by 1 day intended for elimination of the drug from the body (wash-out). The order of treatment periods (morphine -> placebo, placebo -> morphine) will be randomized for each patient by a hospital pharmacist using online software: Research Randomizer 4.0. The draw will assign the participant to one of two sequences: A. 2 days - 0.9% NaCl; 1 day - wash-out; 2 days - morphine hydrochloride. B. 2 days - morphine hydrochloride; 1 day - wash-out; 2 days - 0.9% NaCl
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Drug<br>Morphine hydrochloride | Drug: Morphine hydrochloride<br>* 5 mg milligram(s) per day per two days of dosage<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Inhalation use<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary end point is a reduction of breathlessness intensity by ≥20 mm at 100 mm visual analogue scale (VAS) after nebulization, during daily, normal activities | The primary end point is a reduction of breathlessness intensity by ≥20 mm at 100 mm visual analogue scale (VAS) after nebulization, during daily, normal activities | Breathlessness during daily, normal activities will be measured with VAS 1 hour before nebulization and 4 hours after | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary end point | Secondary end points are: reduction of breathlessness intensity by ≥20 mm at 100 mm visual analogue scale (VAS) following six minute walking test (6MWT) performed after nebulization improvement of 6MWT distance by ≥30 m reduction of cough severity by ≥17 mm at 100 mm visual analogue scale (VAS) after nebulization, during normal activities reduction of chest pain severity by ≥19 mm at 100 mm visual analogue scale (VAS) after nebulization, during normal activities reduction of cough severity by ≥17 mm at 100 mm visual analogue scale (VAS) during six minute walking test (6MWT) performed after nebulization reduction of chest pain severity by ≥19 mm at 100 mm visual analogue scale (VAS) following six minute walking test (6MWT) performed after nebulization | Cough and chest pain severity during normal activities will be assessed with VAS 1h before nebulization and 4 hours after Six minute walking test, along with breathlessness, cough and chest pain assessment in VAS, will be performed 1h before nebuli |