Morphine for Treatment of Dyspnea in Patients With COPD

NCT02429050 | Completed Phase 4

• 2 other identifiers: 15200280-83600-98-3006
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 1

Brief Summary

Dyspnea is the most reported symptom of patients with advanced Chronic Obstructive Pulmonary Disease (COPD) and is undertreated. Morphine is an effective treatment for dyspnea and is recommended in clinical practice guidelines, but questions concerning benefits and concerns about respiratory adverse effects remain. For example, the effect on health-related quality of life and functional capacity is unknown. In one-third of the patients oral sustained release morphine (morphine SR) doesn't relieve dyspnea and it remains unknown whether severity and descriptors of breathlessness may predict a response to morphine. Finally, cost-effectiveness of morphine SR in this patient group is unknown. Therefore, prescription of morphine to patients with COPD is limited. Objectives of this double blind randomized controlled trial are to study the effect of oral administration of morphine SR on health-related quality of life, respiratory adverse effects, and functional capacity; to explore whether description and severity of breathlessness are related with a clinically relevant response to morphine and to analyse the cost-effectiveness of morphine SR. The study population will consist of 124 clinically stable outpatients with COPD and severe dyspnea despite optimal pharmacological and non-pharmacological treatment.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

Chronic Obstructive Pulmonary Disease; Dyspnea; Breathlessness; Morphine; Opioid; Symptom Management

Outcome Measures

Primary Outcomes (7)

• Disease-specific health-related quality of life (COPD Assessment Test (CAT))

  Change in disease-specific health-related quality of life in four weeks measured with CAT

  sixteen weeks

• Change in partial pressure of CO2 (pCO2)

  Change in pCO2 in four weeks

  four weeks

• Change in partial pressure of O2 (pO2)

  Change in pO2 in four weeks

  four weeks

• Respiratory rate

  Change in respiratory rate in four weeks

  four weeks

• Pulse oximetric saturation (SpO2)

  Change in SpO2 in four weeks

  four weeks

• Transcutaneous carbon dioxide (PtcCO2)

  Change in PtcCO2 in four weeks

  four weeks

• Oxygen saturation during the night

  Change in oxygen saturation during the night in four weeks using overnight oximetry

  four weeks

Secondary Outcomes (12)

• distance walked in 6 Minute Walking Test (6-MWT)

  four weeks

• Care dependency (Care Dependency Scale (CDS)

  four weeks

• Mobility (Timed 'Up & Go' (TUG) test)

  four weeks

• Sensory and affective dimensions of dyspnea (Multidimensional Dyspnea Profile (MDP)

  four weeks

• Impact of dyspnea (Pulmonary Functional Status and Dyspnea Questionnaire, PFSDQ-M)

  four weeks

Study Arms (2)

intervention

ACTIVE COMPARATOR

sustained release morphine

Drug: sustained release morphine

control

PLACEBO COMPARATOR

placebo

Drug: placebo

Interventions

sustained release morphine DRUG

Patients will receive morphine SR 10mg two to three times daily or placebo. Hard gelatin capsules of size AA in Swedish orange containing one morphine SR tablet 10 mg per capsule will be produced. Morphine SR has a marketing authorisation for pain and will be used according to current Dutch and international guidelines for treatment of dyspnea.

intervention

placebo DRUG

Patients in the control group will receive placebo, consisting of microcrystalline cellulose (FMC BioPolymer). Hard gelatin capsules of size AA in Swedish orange containing microcrystalline cellulose will be produced.

control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of COPD according to the current Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (GOLD);
• Optimal pharmacological treatment, including including treatment with a combination of a long-acting muscarinic antagonist and an ultra-long-acting β-agonist;
• Grade 3 or 4 dyspnea on the mMRC dyspnea scale;
• Optimal non-pharmacological treatment defined as completed a comprehensive pulmonary rehabilitation program.

You may not qualify if:

• History of substance misuse;
• Exacerbation of COPD within two weeks of study enrolment;
• Waiting list for lung transplantation;
• Pregnant or childbearing potential not using contraception;
• Renal failure (creatinine clearance \<15mL/min);
• Not being able to read or fill in the questionnaires or diary;
• Allergy for morphine or its excipients;
• Concomitant use of irreversible MAO blockers;
• Use of opioids;
• History of convulsions;
• Head injury;
• Intestinal obstruction;
• Gastroparesis;
• Liver disease.

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

Study Sites (1)

Ciro centre of expertise for chronic organ failure

Horn, 6080 AA, Netherlands

Location

Related Publications (2)

• Verberkt CA, van den Beuken-van Everdingen MHJ, Dirksen CD, Schols JMGA, Wouters EFM, Janssen DJA. Cost-effectiveness of sustained-release morphine for refractory breathlessness in COPD: A randomized clinical trial. Respir Med. 2021 Apr;179:106330. doi: 10.1016/j.rmed.2021.106330. Epub 2021 Feb 10.

  PMID: 33611087 DERIVED

• Verberkt CA, van den Beuken-van Everdingen MHJ, Schols JMGA, Hameleers N, Wouters EFM, Janssen DJA. Effect of Sustained-Release Morphine for Refractory Breathlessness in Chronic Obstructive Pulmonary Disease on Health Status: A Randomized Clinical Trial. JAMA Intern Med. 2020 Oct 1;180(10):1306-1314. doi: 10.1001/jamainternmed.2020.3134.

  PMID: 32804188 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Dyspnea

Condition Hierarchy (Ancestors)

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

Study Officials

• Daisy JA Janssen, MD, PhD

  Maastricht UMC

  PRINCIPAL INVESTIGATOR

• E. FM Wouters, MD, PhD

  Maastricht UMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2015
• First Posted: April 29, 2015
• Study Start: November 16, 2016
• Primary Completion: March 6, 2019
• Study Completion: July 1, 2019
• Last Updated: September 4, 2019

Record last verified: 2019-03

Locations

NL (1)