COPD Clinical Trial
— MoreFoRCOPDOfficial title:
Morphine or Fentanyl for Refractory Dyspnea in COPD
Verified date | June 2024 |
Source | University Medical Center Groningen |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Active, not recruiting |
Enrollment | 59 |
Est. completion date | August 24, 2024 |
Est. primary completion date | May 24, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
Netherlands | Noordwest Ziekenhuisgroep Alkmaar | Alkmaar | Noord-Holland |
Netherlands | Wilhelmina Ziekenhuis Assen | Assen | Drenthe |
Netherlands | Rode Kruis Ziekenhuis | Beverwijk | Noord-Holland |
Netherlands | Medisch Spectrum Twente | Enschede | Overijssel |
Netherlands | University Medical Center Groningen | Groningen | |
Netherlands | Spaarne Gasthuis | Haarlem | Noord-Holland |
Netherlands | Elkerliek Ziekenhuis | Helmond | Noord-Brabant |
Netherlands | Ikazia Ziekenhuis | Rotterdam | Zuid-Holland |
Netherlands | Ommelander Ziekenhuis Groningen | Scheemda | Groningen |
Netherlands | Isala Klinieken | Zwolle | Overijssel |
Lead Sponsor | Collaborator |
---|---|
Huib A.M. Kerstjens | Dutch Foundation for Asthma Prevention, Innovatiefonds Zorgverzekeraars |
Netherlands,
Abernethy AP, Currow DC, Frith P, Fazekas BS, McHugh A, Bui C. Randomised, double blind, placebo controlled crossover trial of sustained release morphine for the management of refractory dyspnoea. BMJ. 2003 Sep 6;327(7414):523-8. doi: 10.1136/bmj.327.7414.523. — View Citation
Allan L, Hays H, Jensen NH, de Waroux BL, Bolt M, Donald R, Kalso E. Randomised crossover trial of transdermal fentanyl and sustained release oral morphine for treating chronic non-cancer pain. BMJ. 2001 May 12;322(7295):1154-8. doi: 10.1136/bmj.322.7295.1154. — View Citation
Blinderman CD, Homel P, Billings JA, Tennstedt S, Portenoy RK. Symptom distress and quality of life in patients with advanced chronic obstructive pulmonary disease. J Pain Symptom Manage. 2009 Jul;38(1):115-23. doi: 10.1016/j.jpainsymman.2008.07.006. Epub 2009 Feb 20. — View Citation
Currow DC, McDonald C, Oaten S, Kenny B, Allcroft P, Frith P, Briffa M, Johnson MJ, Abernethy AP. Once-daily opioids for chronic dyspnea: a dose increment and pharmacovigilance study. J Pain Symptom Manage. 2011 Sep;42(3):388-99. doi: 10.1016/j.jpainsymman.2010.11.021. Epub 2011 Mar 31. — View Citation
Hui D, Kilgore K, Frisbee-Hume S, Park M, Liu D, Balachandran DD, Bruera E. Effect of Prophylactic Fentanyl Buccal Tablet on Episodic Exertional Dyspnea: A Pilot Double-Blind Randomized Controlled Trial. J Pain Symptom Manage. 2017 Dec;54(6):798-805. doi: 10.1016/j.jpainsymman.2017.08.001. Epub 2017 Aug 10. — View Citation
Janssen DJ, de Hosson SM, bij de Vaate E, Mooren KJ, Baas AA. Attitudes toward opioids for refractory dyspnea in COPD among Dutch chest physicians. Chron Respir Dis. 2015 May;12(2):85-92. doi: 10.1177/1479972315571926. Epub 2015 Feb 12. — View Citation
Jennings AL, Davies AN, Higgins JP, Gibbs JS, Broadley KE. A systematic review of the use of opioids in the management of dyspnoea. Thorax. 2002 Nov;57(11):939-44. doi: 10.1136/thorax.57.11.939. — View Citation
Jensen D, Alsuhail A, Viola R, Dudgeon DJ, Webb KA, O'Donnell DE. Inhaled fentanyl citrate improves exercise endurance during high-intensity constant work rate cycle exercise in chronic obstructive pulmonary disease. J Pain Symptom Manage. 2012 Apr;43(4):706-19. doi: 10.1016/j.jpainsymman.2011.05.007. Epub 2011 Dec 14. — View Citation
Johnson MJ, Bland JM, Oxberry SG, Abernethy AP, Currow DC. Clinically important differences in the intensity of chronic refractory breathlessness. J Pain Symptom Manage. 2013 Dec;46(6):957-63. doi: 10.1016/j.jpainsymman.2013.01.011. Epub 2013 Apr 19. — View Citation
Payne R, Mathias SD, Pasta DJ, Wanke LA, Williams R, Mahmoud R. Quality of life and cancer pain: satisfaction and side effects with transdermal fentanyl versus oral morphine. J Clin Oncol. 1998 Apr;16(4):1588-93. doi: 10.1200/JCO.1998.16.4.1588. — View Citation
Simon ST, Koskeroglu P, Gaertner J, Voltz R. Fentanyl for the relief of refractory breathlessness: a systematic review. J Pain Symptom Manage. 2013 Dec;46(6):874-86. doi: 10.1016/j.jpainsymman.2013.02.019. Epub 2013 Jun 4. — View Citation
Wiseman R, Rowett D, Allcroft P, Abernethy A, Currow DC. Chronic refractory dyspnoea--evidence based management. Aust Fam Physician. 2013 Mar;42(3):137-40. — View Citation
* Note: There are 12 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Survival | Measured one week after the end of the treatment period | One week after the end of the treatment period, which is 7 weeks after start of the study. | |
Primary | Change in dyspnea sensation | Change in dyspnea sensation measured on a Numeric Rating Scale from 0 to 10. A lower score represents a better outcome. | Daily during the six week treatment period | |
Secondary | Change in CCQ (HR-QoL) | Change in HR-QoL measured with the Clinical COPD Questionnaire. Scores range from 0 to 6. Lower values represent a better outcome. | Daily during the six week treatment period | |
Secondary | Change in CRQ (HR-QoL) | Change in HR-QoL measured with Chronic Respiratory Disease Questionnare. Scores range from 1 to 7. A higher score represents a better outcome. | 4 times during the six week treatment period: baseline, 2 weeks, 4 weeks, 6 weeks. | |
Secondary | Change in CRQ mastery (HR-QoL) | 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 times during the six week treatment period: baseline, 2 weeks, 4 weeks, 6 weeks. | |
Secondary | Change on the HADS-A questionnaire (Anxiety) | Change on the Hospital Anxiety and Depression Scale-anxiety subscale. Scores range from 0 to 21. A lower score represents a better outcome. | 4 times during the six week treatment period: baseline, 2 weeks, 4 weeks, 6 weeks. | |
Secondary | Side effects | Reported spontaneously in a daily patient diary and specifically, both open and named side effects at planned visits. | Daily during the six week treatment period | |
Secondary | Hypercapnia | Change in pCO2 in capillary blood gas analysis | 4 times during the six week treatment period: baseline, 2 weeks, 4 weeks, 6 weeks. | |
Secondary | Sleep quality | Change on a Numeric Rating Scale from 0 to 10. A lower score represents a better outcome. | Daily during the six week treatment period | |
Secondary | Continued opioid use | Asked three months after the end of the treatment period | Once, three months after the end of the treatment period |
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