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Morphine or Fentanyl for Refractory Dyspnea in COPD (MoreFoRCOPD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03834363
Recruitment Status : Recruiting
First Posted : February 7, 2019
Last Update Posted : January 22, 2020
Sponsor:
Collaborators:
Dutch Foundation for Asthma Prevention
Innovatiefonds Zorgverzekeraars
Information provided by (Responsible Party):
Huib A.M. Kerstjens, University Medical Center Groningen

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
COPD Drug: Fentanyl Drug: Morphine Retard Drug: Placebo patch Drug: Placebo oral capsule Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Crossover, 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 : November 15, 2019
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine


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 Name: 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 Name: 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




Primary Outcome Measures :
  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 Outcome Measures :
  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 Outcome Measures:
  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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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): NCT03834363


Contacts
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Contact: Marlies van Dijk, MD +31503612357 m.van.dijk05@umcg.nl
Contact: Huib AM Kerstjens, MD PhD +31503610280 h.a.m.kerstjens@umcg.nl

Locations
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Netherlands
Wilhelmina Ziekenhuis Assen Not yet recruiting
Assen, Drenthe, Netherlands, 9401 RK
Contact: Sander De Hosson, MD         
Principal Investigator: Sander De Hosson, MD         
Ommelander Ziekenhuis Groningen Recruiting
Scheemda, Groningen, Netherlands, 9676 BJ
Principal Investigator: Jan Willem De Jong, MD PhD         
Elkerliek Ziekenhuis Recruiting
Helmond, Noord-Brabant, Netherlands, 5707 HA
Contact: Wai Yee Lam, MD PhD         
Principal Investigator: Wai Yee Lam, MD PhD         
Noordwest Ziekenhuisgroep Alkmaar Not yet recruiting
Alkmaar, Noord-Holland, Netherlands, 1815 JD
Contact: Liesbeth Peters, MD         
Principal Investigator: Liesbeth Peters, MD         
Rode Kruis Ziekenhuis Not yet recruiting
Beverwijk, Noord-Holland, Netherlands, 1942 LE
Contact: Karin Pool, MD         
Principal Investigator: Karin Pool, MD         
Spaarne Gasthuis Not yet recruiting
Haarlem, Noord-Holland, Netherlands, 2035 RC
Contact: Kris Mooren, MD         
Principal Investigator: Kris Mooren, MD         
Medisch Spectrum Twente Not yet recruiting
Enschede, Overijssel, Netherlands, 7512 KZ
Contact: Wendy Van Beurden, MD         
Principal Investigator: Wendy van Beurden, MD         
Isala Klinieken Not yet recruiting
Zwolle, Overijssel, Netherlands, 8025 AB
Contact: Jan Willem Van den Berg, MD PhD         
Principal Investigator: Jan WIllem Van den Berg, MD PhD         
Ikazia Ziekenhuis Recruiting
Rotterdam, Zuid-Holland, Netherlands, 3083 AN
Contact: Roxane Heller-Baan, MD         
Principal Investigator: Roxane Heller-Baan, MD         
University Medical Center Groningen Recruiting
Groningen, Netherlands, 9713GZ
Contact: Huib A.M. Kerstjens, MD PhD         
Principal Investigator: Huib A.M. Kerstjens, MD PhD         
Sub-Investigator: Marlies van Dijk, MD         
Sponsors and Collaborators
Huib A.M. Kerstjens
Dutch Foundation for Asthma Prevention
Innovatiefonds Zorgverzekeraars

Publications:

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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: February 7, 2019    Key Record Dates
Last Update Posted: January 22, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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, University Medical Center Groningen:
COPD
Refractory Dyspnea
Morphine
Fentanyl
Additional relevant MeSH terms:
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Dyspnea
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Fentanyl
Morphine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adjuvants, Anesthesia
Anesthetics, Intravenous
Anesthetics, General
Anesthetics