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Morphine Sulfate/Placebo for the Treatment of PulmonAry Fibrosis Cough (PAciFy Cough)

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ClinicalTrials.gov Identifier: NCT04429516
Recruitment Status : Recruiting
First Posted : June 12, 2020
Last Update Posted : March 10, 2021
Sponsor:
Information provided by (Responsible Party):
Royal Brompton & Harefield NHS Foundation Trust

Brief Summary:

Idiopathic pulmonary fibrosis (IPF) is a disease of unknown cause that results in scarring of the lungs.

Cough is reported by 85% of patients with IPF and can be a distressing symptom with significant physical, social and psychological consequences particularly anxiety and depression.

The cause of cough in IPF is poorly understood and there are currently no proven effective therapies. Morphine has long been advocated for the suppression of chronic cough in other conditions. While morphine is frequently used as a palliative agent for breathlessness in IPF, its effects on cough have never been tested. The aim of this study is therefore to explore and compare the effect of low dose morphine, one of the few therapies shown to be effective in some patients with otherwise refractory chronic cough, in patients with IPF, to an inactive substance known as a placebo.

To make a fair comparison, patients will be randomly allocated to receiving either morphine or placebo in a blinded fashion. This means neither the doctor nor the patient will know which drug they are receiving, and the drugs will appear the same. However, the trial is designed so that you will receive both morphine and placebo, but at different times (this is called a cross-over study). More specifically, you will be given either morphine or placebo for 14 days at a time.

In this study, it is hypothesised that compared with placebo, low dose (5mg) controlled release Morphine sulfate (MST) will reduce the number of coughs recorded during a 24hr period in patients with IPF.


Condition or disease Intervention/treatment Phase
Idiopathic Pulmonary Fibrosis Drug: Morphine Sulfate Drug: Placebo oral tablet Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: PAciFy Cough: A Multicentre, Double Blind, Placebo Controlled, Crossover Trial of Morphine Sulfate for the Treatment of PulmonAry Fibrosis Cough
Actual Study Start Date : December 17, 2020
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : August 2022


Arm Intervention/treatment
Experimental: Morphine Sulfate Drug: Morphine Sulfate
over-encapsulated Morphine Sulfate prolonged release 5mg tablet, twice daily for 14 days. Patients will then crossover after a 7 day wash out period.

Placebo Comparator: Placebo Drug: Placebo oral tablet
capsule containing Microcrystalline Cellulose Ph. Eur, 5 mg twice daily




Primary Outcome Measures :
  1. The percent change in daytime cough frequency (coughs per hour) [ Time Frame: from baseline as assessed by objective digital cough monitoring at Day 14 of treatment ]

Secondary Outcome Measures :
  1. Change from baseline in health-related quality of life scores (Living with Idiopathic Pulmonary Fibrosis Questionnaire) [ Time Frame: At Day 0, Day 14, Day 22, Day 36 and Day 50-64 ]
    Living with Idiopathic Pulmonary Fibrosis (L-IPF): Developing a Patient-Reported Symptom and Impact Questionnaire to Assess Health-Related Quality of Life in IPF; on a scale between 0 to 4, where 0 is Not at all and 4 is Extremlly.

  2. Change from baseline in health-related quality of life scores (HDAS- Hospital Anxiety and Depression Scale) [ Time Frame: At Day 0, Day 14, Day 22, Day 36 and Day 50-64 ]
    HADS - Hospital Anxiety and Depression Scale (Scoring 0-7 = Normal 8-10 = Borderline abnormal (borderline case) 11-21 = Abnormal (case).

  3. Change from baseline in health-related quality of life scores (K-BILD - King's Brief Interstitial Lung Disease Questionnaire) [ Time Frame: At Day 0, Day 14, Day 22, Day 36 and Day 50-64 ]
    The KBILD is a self-completed health status questionnaire that comprises 15 items and a seven-point Likert response scale. It has three domains: psychological, breathlessness and activities and chest symptoms. The KBILD domain and total score ranges are 0-100; 100 represents best health status.

  4. Change from baseline in self-reported cough (Leicester Cough Questionnaire (LCQ) [ Time Frame: At Day 0, Day 14, Day 22, Day 36 and Day 50-64 ]
    The Leicester Cough Questionnaire comprises of 19 questions, each on a score between 1 to 7, the latter meaning worse outcome. 8 of the questions assess the physical cough domain, 7 items assess the psychological impact of cough, and 4 questions assess the social impact of cough.

  5. Change from baseline in self-reported cough - Visual analogue scale (VAS) [ Time Frame: At Day 0, Day 14, Day 22, Day 36 and Day 50-64 ]
    VAS - The cough visual analogue scale (VAS) represents a simple instrument, using a 100 mm linear scale where patient can indicate the severity of their cough between the two extremes: zero is no cough while 100 mm is the worst cough imaginable.

  6. Change from baseline in Dyspnoea (Dyspnoea 12) [ Time Frame: At Day 0, Day 14, Day 22, Day 36 and Day 50-64 ]
    D-12 consists of 12 descriptor items on a scale of none (0), mild (1), moderate (2), or severe (3). It provides an overall score for breathlessness severity that incorporates seven physical items and five affective items

  7. Change from baseline in global impression of change in quality of life, cough and breathlessness. [ Time Frame: At Day 14 and Day 36 ]
    It provides a brief, stand-alone assessment of treatment effect on cough, breathlessness and overall quality of live on a scale of: worse, same and better.

  8. Proportion of responders with a minimum of 20% decrease from baseline at the end of treatment in 24-hour average cough count. [ Time Frame: Comparison made between pre-treatment and at follow up visit in both the first and then the crossover arms of the study: Day 0, Day 14, Day 22 and Day 36 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Self-reported cough (> 8 weeks), with cough VAS ≥ 30/100
  2. A diagnosis of IPF within 5 years prior to the screening visit, as per applicable ATS/ERS/JRS/ALAT guidelines, in line with hospital records.
  3. Age 3.1. Male and female participants aged ≥ 40 - 90 years at the time of signing informed consent
  4. Sex:

    4.1 Male participants: A male participant must agree to use contraception as detailed in Appendix 2 of this protocol during the study and for at least 90 days after the follow-up visit, and refrain from donating sperm during this period 4.2 Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and not a woman of childbearing potential (WOCBP)

  5. Meeting all of the following criteria during the screening period: FVC ≥ 45% predicted of normal, Forced expiratory volume in 1 second (FEV1)/FVC ≥0.7, DLCO corrected for Hb ≥30% predicted of normal.
  6. The extent of fibrotic changes is greater than the extent of emphysema on the most recent HRCT scan (investigator determined within 24 months of the study screening visit)
  7. Written informed consent.

Exclusion criteria:

  1. Treatment with immunosuppressive therapy or antibiotics within last 4 weeks. A stable dose of corticosteroids equivalent to prednisolone of 10 mg per day or less, if used for an indication other than pulmonary disease will be permitted
  2. Current smoker
  3. History of alcohol and drug(s) addiction
  4. Regular use of sedative therapies
  5. Acute IPF exacerbation within 6 months prior to screening and/or during the screening period.
  6. Concurrent use of pirfenidone or Nintedanib, unless receiving a stable dose for at least 8 weeks prior to screening
  7. Use of ACE inhibitors
  8. Patients with co-existent conditions know to be associated with the development of fibrotic lung disease. This includes: connective tissue disease, (plural plaques, mesothelioma), granulomatous disease including sarcoidosis. Patient with auto-immune profile considered diagnostic for a specific connective tissue disease will be excluded, even in the absence of systemic symptoms. Non-specific rises in auto antibodies e.g. rheumatoid factors, anti-nuclear antibody etc. will not be used to exclude individuals from the study.
  9. Significant other organ co-morbidity including hepatic or renal impairment and pulmonary hypertension (investigator determined).
  10. Significant coronary artery disease (myocardial infarction within 6 months or ongoing unstable angina within 4 weeks of screening visit) or congestive cardiac failure based on clinical examination
  11. Patients as significant risk of side effects, intolerance or allergy to morphine
  12. Pregnant and breastfeeding patients, or women or child-bearing potential, not using a reliable contraceptive method (see Appendix 2). A urine pregnancy test will be performed in females of child-bearing potential at the initial study visit.
  13. Unable to provide informed written consent
  14. Predicted life expectancy < 6 months
  15. Use of long-term oxygen therapy. Use of ambulatory oxygen will be permitted.
  16. Current or use of opiates within 14 days of the screening visit.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04429516


Contacts
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Contact: Philip Molyneaux, DR 0207 351 8121 p.molyneaux@rbht.nhs.uk

Locations
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United Kingdom
Royal Brompton Hospital Recruiting
London, United Kingdom, SW3 6NP
Contact: Philip Molyneaux, DR    0207 351 8121    P.Molyneaux@rbht.nhs.uk   
Sponsors and Collaborators
Royal Brompton & Harefield NHS Foundation Trust
Publications:
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Responsible Party: Royal Brompton & Harefield NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT04429516    
Other Study ID Numbers: RBH2019/001
2019-003571-19 ( EudraCT Number )
First Posted: June 12, 2020    Key Record Dates
Last Update Posted: March 10, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Fibrosis
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Morphine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents