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NCT Number: NCT03834363

Morphine or Fentanyl for Refractory Dyspnea in COPD

Rationale: The most important complaint in severe COPD is dyspnea which is associated with a diminished exercise tolerance, reduced quality of life and can lead to anxiety and depression. If dyspnea continues to exist despite optimal therapy it is called refractory dyspnea. There is evidence that morphine is effective and can safely be prescribed for treating refractory dyspnea.

However, a Dutch study recently showed that few pulmonologists actually prescribe opioids for this indication. The main reasons for this are concerns about side effects and respiratory insufficiency as well as negative emotions for the patient and families at the thought of using morphine.

Most studies investigating opioids for treatment of dyspnea are conducted with morphine tablets, and only a part of these patients suffered from COPD. To our knowledge there has not been a randomized controlled trial investigating fentanyl patches for refractory dyspnea in COPD patients. However, studies comparing fentanyl and morphine in pain management show that patients may prefer fentanyl patches and have less problems with obstipation.

Objective: There are three main objectives for this study.

First, the investigators will investigate the following hypothesis: Both fentanyl and morphine provide a reduction of dyspnea which is better than placebo. Fentanyl has less side effects than morphine.

Secondly, with this Dutch multi-center study the investigators would like to enlarge the evidence base and contribute to the experience with opioids for refractory dyspnea in COPD thereby greatly facilitating its implementation in the Netherlands.

Finally, the investigators will develop and evaluate educational material about opioid use for dyspnea in COPD.

Study design: This is a multi-center double blind, double-dummy cross-over randomized placebo-controlled trial with three study arms. A total of 60 COPD patients will be included in this study.

Participants will be treated sequentially with three combinations of medication and/or placebo medication in a random order. They will receive either a Fentanyl patch in combination with placebo tablets, a placebo patch with Morphine Slow release tablets or a placebo patch with placebo tablets. Main study parameters/endpoints: The primary endpoint is change in dyspnea sensation Secondary endpoints are change in HR-QoL, anxiety, sleep quality, hypercapnia and the number and seriousness of side effect.

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Key information

Conditions

COPD Chronic Disease Disease Attributes Dyspnea Lung Diseases Lung Diseases, Obstructive Pathologic Processes Pathological Conditions, Signs and Symptoms Pulmonary Disease, Chronic Obstructive Respiration Disorders Respiratory Tract Diseases Signs and Symptoms Signs and Symptoms, Respiratory

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Wilhelmina Ziekenhuis Assen, Assen, Drenthe, Netherlands

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age ≥ 40 years.
  • Read, understood and signed the Informed Consent form.
  • COPD GOLD class III or IV, according to GOLD criteria (Post-bronchodilation FEV/FVC <70% and FEV1 < 50%pred.
  • Complaints of refractory dyspnea as established by patient and doctor.
  • mMRC score ≥ 3.
  • Life expectancy of ≥ 2 months.
  • Optimized standard therapy according to Dutch LAN guideline for diagnosis and treatment of COPD.

Exclusion criteria

  • Other severe disease with chronic pain or chronic dyspnea (a non substantial component of left sided heart failure is acceptable).
  • Current use of opioids for whatever indication.
  • Allergy / intolerance for opioids
  • Psychiatric disease, not related to severe COPD.
  • Exacerbation of COPD 8 weeks prior to inclusion or between screening and randomization.
  • Problematic (leading to medical help or social problems) substance abuse during the last five years.
  • Active malignancy, with the exception of planocellular or basal cell carcinoma of the skin.
  • eGFR <15 ml/min

Treatment and study plan

Fentanyl

Drug

Fentanylpatch 12 mcg/hr, change patch every three days.

Other names: Fentanyl Matrix

Morphine Retard

Drug

Morphine retard capsules 10 mg bid.

Other names: Morphine

Placebo Patch

Drug

Placebo patch, change patch every three days.

Placebo oral capsule

Drug

Placebo oral capsule bid

Primary outcomes

  1. Change in dyspnea sensation

    Time frame: Daily during the six week treatment period

    Change in dyspnea sensation measured on a Numeric Rating Scale from 0 to 10. A lower score represents a better outcome.

Secondary outcomes

  1. Change in CCQ (HR-QoL)

    Time frame: Daily during the six week treatment period

    Change in HR-QoL measured with the Clinical COPD Questionnaire. Scores range from 0 to 6. Lower values represent a better outcome.

  2. Change in CRQ (HR-QoL)

    Time frame: 4 times during the six week treatment period: baseline, 2 weeks, 4 weeks, 6 weeks.

    Change in HR-QoL measured with Chronic Respiratory Disease Questionnare. Scores range from 1 to 7. A higher score represents a better outcome.

  3. Change in CRQ mastery (HR-QoL)

    Time frame: 4 times during the six week treatment period: baseline, 2 weeks, 4 weeks, 6 weeks.

    Change in HR-QoL measured with Chronic Respiratory Disease Questionnare, domain Mastery. Scores range from 1 to 7. A higher score represents a better outcome.

  4. Change on the HADS-A questionnaire (Anxiety)

    Time frame: 4 times during the six week treatment period: baseline, 2 weeks, 4 weeks, 6 weeks.

    Change on the Hospital Anxiety and Depression Scale-anxiety subscale. Scores range from 0 to 21. A lower score represents a better outcome.

  5. Side effects

    Time frame: Daily during the six week treatment period

    Reported spontaneously in a daily patient diary and specifically, both open and named side effects at planned visits.

  6. Hypercapnia

    Time frame: 4 times during the six week treatment period: baseline, 2 weeks, 4 weeks, 6 weeks.

    Change in pCO2 in capillary blood gas analysis

  7. Sleep quality

    Time frame: Daily during the six week treatment period

    Change on a Numeric Rating Scale from 0 to 10. A lower score represents a better outcome.

  8. Continued opioid use

    Time frame: Once, three months after the end of the treatment period

    Asked three months after the end of the treatment period

Other outcomes

  1. Survival

    Time frame: One week after the end of the treatment period, which is 7 weeks after start of the study.

    Measured one week after the end of the treatment period

Sponsors and collaborators

Lead sponsor

Huib A.M. Kerstjens

Other

Collaborators

  • Dutch Foundation for Asthma Prevention
  • Innovatiefonds Zorgverzekeraars

Registry information

Acronym: MoreFoRCOPD

Important dates

Study start
2019
Primary completion
2024
Study completion
2024
First posted
Feb 7, 2019
Registry last updated
Jun 4, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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