Condition category
Respiratory
Date applied
07/03/2017
Date assigned
23/03/2017
Last edited
23/03/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Chronic obstructive pulmonary disease (COPD) is the name given to a collection of diseases which affect the lungs. It is characterised by breathlessness, cough and excess mucus production and is often caused by smoking. Almost all patients with COPD experience dyspnea (difficulty breathing) in their last year of life. Opiod medications (pain relievers such as morphine) are usually offered for end of life care at this stage of the disease. Some small-scale studies support the use of nebulisers (machines which turn drugs into a mist so they can be inhaled into the lungs) to deliver morphine as an alternative treatment for dyspnea. Reports show that delivering morphine in this way can cause less side effects, such as constipation or dizziness. Unfortunately, the effectiveness of nebulized morphine has not been confirmed in larger studies. Recent studies have shown that a large amount of opioid receptors (proteins that bind to opioids and send signals to the brain) are found in the lining of the large airways (windpipe and bronchi - tubes into the lungs). The aim of this study is to compare the effectiveness of nebulized morphine and nebulized saline (salt water), both delivered by the same inhalation system calibrated to target large airways, in treating dyspnea in severe COPD.

Who can participate?
Patients over 50 years old who have severe COPD with dyspnea.

What does the study involve?
During an eight-day stay in hospital, patients receive four days of treatment with nebulized morphine and four days of treatment with nebulized saline in a random order using a special inhalation system designed to target the large airways (wind pipe and bronchi - tubes into the lungs). The intensity of breathlessness is rated on a continuous, 100 mm scale by patients. In addition, the patient's exercise tolerance is measured by a number reading test, which involves asking patients to read numbers aloud for 60 seconds as quickly and clearly as possible, and lung function is measured using specialised equipment.

What are the possible benefits and risks of participating?
Participants may benefit from an improvement to their breathlessness symptoms. There is a small risk of side effects from the nebulized morphine, such as cough, bitter taste or a pricking sensation in the throat. In rare cases patients may develop tightening of the airways or an allergic reaction.

Where is the study run from?
University Clinical Centre in Gdansk (Poland)

When is the study starting and how long is it expected to run for?
May 2012 to December 2016

Who is funding the study?
Medical University of Gdańsk (Poland)

Who is the main contact?
Dr Piotr Janowiak
33033@gumed.edu.pl.

Trial website

Contact information

Type

Scientific

Primary contact

Mr Piotr Janowiak

ORCID ID

http://orcid.org/0000-0001-7941-465X

Contact details

University Clinical Centre
Department of Allergology and Pneumonology
ul. Dębinki 7
Gdańsk
80-952
Poland
+48 58 349 26 25
33033@gumed.edu.pl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

ST-553

Study information

Scientific title

Dosimetrically administered nebulized morphine for breathlessness in very severe chronic obstructive pulmonary disease

Acronym

Study hypothesis

2% morphine hydrochloride water solution, nebulized by dosimetric nebulizer calibrated to target large airways, is superior to 0.9% NaCl delivered by the same equipment in treating severe dyspnea in chronic obstructive pulmonary disease.

Ethics approval

Independent Bioethics Committee for Research of Medical University of Gdansk, 25/06/2012, ref: NKBBN/269/2012

Study design

Single-centre randomized double-blind controlled, cross-over trial

Primary study design

Interventional

Secondary study design

Randomised cross over trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Breathlessness in very severe chronic obstructive pulmonary disease

Intervention

Patients are randomly assigned to two treatment sequences using online software for simple randomization (Research Randomizer ver. 3.0).

Each sequence lasts for eight days and consists of two periods, each lasting four days. There is no wash-out between periods. During each period different drug is nebulized: 2% morphine hydrochloride water solution or 0.9% NaCl. Both substances are delivered once daily, in a titrated manner, with the same dosimetric nebulizer until the clinically significant response (i.e. ≥20mm drop in VAS) is reached or substantial side effects occur. MF doses for 4 consecutive days are: 1, 2, 3 and 5 mg.

Intervention type

Drug

Phase

Not Applicable

Drug names

Morphine hydrochloride

Primary outcome measures

Intensity of breathlessness, measured by visual analogue scale (VAS) 15-30 minutes before the nebulisation, immediately after the nebulisation and 15 minutes, 30 minutes, 1, 2, 3 and 4 hours after the nebulization.

Secondary outcome measures

1. Most effective dose of morphine is noted when ≥20 mm drop in VAS is detected
2. Exercise tolerance is measured using the Wilcock’s test 15-30 minutes before and 2 hours after nebulization
3. Safety is assessed by measuring heart rate, respiratory rate and peripheral capillary oxygen saturation at the same time points as VAS, and spirometry and peak expiratory flow (PEF) one hour before and one hour after nebulisation

Overall trial start date

01/05/2012

Overall trial end date

20/12/2016

Reason abandoned

Eligibility

Participant inclusion criteria

1. Age above 50 years
2. COPD group D, according to 2013 Global Initiative For Chronic Obstructive Lung Disease (GOLD) guidelines
3. Stage IV airflow limitation i.e. FEV1% < 30%, according to 2011 GOLD classification
4. Breathlessness rated 3 or 4 in the modified Medical Research Council scale (mMRC) breathlessness scale
5. Current non-smoker
6. Written informed consent

Participant type

Patient

Age group

Mixed

Gender

Both

Target number of participants

10

Participant exclusion criteria

1. Other coexisting severe chronic lung diseases, such as lung cancer
2. Breathlessness caused by other than COPD chronic diseases, such as heart failure or renal failure
3. Inability to give informed consent
4. previous history of respiratory depression after opioid administration or allergic reactions to opioids
5. Ongoing opioid treatment for any indication
6. COPD exacerbation within the last month

Recruitment start date

04/03/2014

Recruitment end date

01/03/2016

Locations

Countries of recruitment

Poland

Trial participating centre

University Clinical Centre
Department of Allergology and Pneumonology ul. Dębinki 7
Gdańsk
80-952
Poland

Sponsor information

Organisation

Medical University of Gdańsk

Sponsor details

ul. M. Skłodowskiej-Curie 3a
Gdańsk
80-210
Poland
+48 58 349 11 11
info@gumed.edu.pl

Sponsor type

University/education

Website

https://mug.edu.pl/

Funders

Funder type

University/education

Funder name

Medical University of Gdańsk

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal.

IPD Sharing plan:
The datasets generated during and/or analysed during the current study are/will be available upon request from Piotr Janowiak (33033@gumed.edu.pl)

Intention to publish date

20/12/2017

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes