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MoreFoRCOPD: Morphine or Fentanyl for Refractory Dyspnea in COPD

Sponsor
Huib A.M. Kerstjens (Other)
Overall Status
Recruiting
CT.gov ID
NCT03834363
Collaborator
Dutch Foundation for Asthma Prevention (Other), Innovatiefonds Zorgverzekeraars (Other)
60
Enrollment
10
Locations
3
Arms
36.5
Anticipated Duration (Months)
6
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Fentanyl
  • Drug: Morphine Retard
  • Drug: Placebo patch
  • Drug: Placebo oral capsule
 Phase 4

Study Design

Study Type:
Interventional
Anticipated Enrollment :
60 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Intervention Model Description:
Crossover, double blind, double dummy Randomized Controlled TrialCrossover, double blind, double dummy Randomized Controlled Trial
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
For both morphine retard capsules as fentanyl patches there is a placebo available. Participants will be treated in each period with both tablets and a patch. (morphine capsules+placebo patch, placebo capsules+fentanyl patch, placebo capsules+ placebo patch.)
Primary Purpose:
Treatment
Official Title:
Morphine or Fentanyl for Refractory Dyspnea in COPD
Actual Study Start Date :
Nov 15, 2019
Anticipated Primary Completion Date :
Oct 1, 2022
Anticipated Study Completion Date :
Dec 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Morphine capsules and Placebo patch

Morphine retard 10 mg twice daily Placebo patch, change every three days.

Drug: Morphine Retard
Morphine retard capsules 10 mg bid.
Other Names:
  • Morphine

    • Drug: Placebo patch
    Placebo patch, change patch every three days.
    Experimental: Placebo capsules and Fentanyl patch

    Placebo capsules twice daily Fentanyl patch 12 mcg/hr, change every three days

    Drug: Fentanyl
    Fentanylpatch 12 mcg/hr, change patch every three days.
    Other Names:
  • Fentanyl Matrix

    • Drug: Placebo oral capsule
    Placebo oral capsule bid
    Placebo Comparator: Placebo capsules and Placebo patch

    Placebo capsules twice daily Placebo patch, change every three days

    Drug: Placebo patch
    Placebo patch, change patch every three days.

    Drug: Placebo oral capsule
    Placebo oral capsule bid

    Outcome Measures

    Primary Outcome Measures

    1. Change in dyspnea sensation [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 Outcome Measures

    1. Change in CCQ (HR-QoL) [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) [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) [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) [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 [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 [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 [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 [Once, three months after the end of the treatment period]

      Asked three months after the end of the treatment period

    Other Outcome Measures

    1. Survival [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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Wilhelmina Ziekenhuis Assen Assen Drenthe Netherlands 9401 RK
    2 Ommelander Ziekenhuis Groningen Scheemda Groningen Netherlands 9676 BJ
    3 Elkerliek Ziekenhuis Helmond Noord-Brabant Netherlands 5707 HA
    4 Noordwest Ziekenhuisgroep Alkmaar Alkmaar Noord-Holland Netherlands 1815 JD
    5 Rode Kruis Ziekenhuis Beverwijk Noord-Holland Netherlands 1942 LE
    6 Spaarne Gasthuis Haarlem Noord-Holland Netherlands 2035 RC
    7 Medisch Spectrum Twente Enschede Overijssel Netherlands 7512 KZ
    8 Isala Klinieken Zwolle Overijssel Netherlands 8025 AB
    9 Ikazia Ziekenhuis Rotterdam Zuid-Holland Netherlands 3083 AN
    10 University Medical Center Groningen Groningen Netherlands 9713GZ

    Sponsors and Collaborators

    • Huib A.M. Kerstjens
    • Dutch Foundation for Asthma Prevention
    • Innovatiefonds Zorgverzekeraars

    Investigators

    • Principal Investigator: Huib AM Kerstjens, MD PhD, University Medical Center Groningen

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Huib A.M. Kerstjens, Full professor pulmonology, head of department pulmonology and tuberculosis, principal investigator., University Medical Center Groningen
    ClinicalTrials.gov Identifier:
    NCT03834363
    Other Study ID Numbers:
    • MoreFoRCOPD
    First Posted:
    Feb 7, 2019
    Last Update Posted:
    Nov 30, 2021
    Last Verified:
    Nov 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Huib A.M. Kerstjens, Full professor pulmonology, head of department pulmonology and tuberculosis, principal investigator., University Medical Center Groningen
    COPD
    Refractory Dyspnea
    Morphine
    Fentanyl
    Additional relevant MeSH terms:
    Dyspnea
    Fentanyl
    Morphine

    Study Results

    No Results Posted as of Nov 30, 2021