Condition category
Digestive System
Date applied
25/03/2015
Date assigned
25/03/2015
Last edited
20/04/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
The drug methylnaltrexone is approved for use in the palliative/end of life care setting for treating constipation caused by opioid drugs. We believe that the use of methylnaltrexone for patients taking opioids will be of even greater benefit for people being treated in intensive care. Opioid drugs are used for the sedation and pain relief required for critically ill patients to tolerate mechanical breathing assistance. Unfortunately, there are considerable side effects including pruritus (itching), suppression of the immune system and most clinically relevant gastrointestinal (bowel) dysfunction. This leads to digestive problems, constipation leading to stomach bloating, a large immobile stool volume in the bowel (faecal impaction) and infection. There are several case reports supporting use of methylnaltrexone in intensive care , and we have used the drug successfully at Hammersmith Hospital. We have published a study showing that a significant number of critical care patients do suffer from opioid induced constipation despite standard treatment given to prevent this. Those patients that were treated with methylnaltrexone opened bowels within 24 hours, a result not achieved with standard therapy. There were also some benefits in the feeding and digestion of food and mortality (death rate) although these were not statistically significant. We now want to carry out a full trial to further investigate whether the drug methylnaltrexone does alleviate constipation caused by opioid drugs for critical care patients.

Who can participate?
Adults (aged at least 18) sedated with opiods and requiring mechanical breathing assistance.

What does the study involve?
Participants are randomly allocated into one of two groups. Those in group 1 receive methylnaltrexone following 48 hours of opioid induced constipation. Those in group 2 receive a placebo following 48 hours of opioid induced constipation. All participants are then followed up every day to assess, among other things, relief of constipation, tolerance of feeding, infection and mortality.

What are the possible benefits and risks of participating?
Methylnaltrexone has been shown to ease constipation in patients with cancer. It would be anticipated that critically ill patients would benefit too. In addition, there is the possibility of additional advantages in more effective feeding, and reversal of some of the detrimental immune effects of opioids. However, at the moment, we do not know if Methylnaltrexone definitely has these benefits or that the side effects will still be rare in this group of patients, which is why we are doing this study. We cannot guarantee taking part in the study will benefit a participant directly but if this study shows a benefit, then it might help improve the treatment of people with constipation and gut dysfunction in the future.
There is little additional risk from taking part in this study, as Methylnaltrexone is very safe with few side effects (nausea, diarrhoea, flatulence, dizziness), and no serious adverse effects have been reported.
Only very small quantities of extra blood samples will be collected, usually from existing lines, so there is no extra discomfort.

Where is the study run from?
Imperial College of Science, Technology and Medicine (UK)

When is the study starting and how long is it expected to run for?
May 2015 to April 2016

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
Miss Aisha Anjum

Trial website

Contact information

Type

Scientific

Primary contact

Miss Aisha Anjum

ORCID ID

http://orcid.org/0000-0001-8346-3382

Contact details

Imperial College of Science
Technology and Medicine
ICCH Building
59 North Wharf Road
London
W2 1LA
United Kingdom

Additional identifiers

EudraCT number

2014-004687-37

ClinicalTrials.gov number

Protocol/serial number

18502

Study information

Scientific title

Use of methylnaltrexone for the treatment of opioid induced constipation & gastroIntestinal stasis in intensive care patients

Acronym

MOTION

Study hypothesis

The aim of this study is to investigate whether the drug methylnaltrexone alleviates constipation caused by opioid drugs for critical care patients.

Ethics approval

NRES Committee London - Harrow, 30/12/2014, 14/LO/2004

Study design

Randomised; Interventional; Design type: Treatment

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

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

Condition

Topic: Critical care; Subtopic: Critical care; Disease: All Critical care

Intervention

Methylnaltrexone (Relistor): Opioid antagonist
Placebo: Normal Saline
Study Entry : Registration and One or More Randomisations

Intervention type

Drug

Phase

Phase IV

Drug names

Methylnaltrexone

Primary outcome measures

Time to significant rescue-free laxation (stool volume of greater than 100mls) following randomisation; Timepoint(s): Daily.

Secondary outcome measures

1.Average number of bowel movements; Timepoint(s): Daily
2. Escalation of opioid dose due to antagonism/reversal of analgesia and sedation; Timepoint(s): Daily
3. Incidence of Clostridium difficile infection: PCR or Toxin positive; Timepoint(s): Daily
4. Incidence of diarrhoea; Timepoint(s): Daily
5. Incidence of positive microbiology blood cultures; Timepoint(s): Daily
6. Incidence of ventilator associated pneumonia (VAP), defined by the Clinical Pulmonary Infection Score; Timepoint(s): Daily
7. Mortality; Timepoint(s): At 28 days, ICU discharge and Hospital discharge
8. Requirement of prokinetics (10mg Metoclopramide tds, 250mg Erythromycin qds); Timepoint(s):. Daily
9. Requirement of rescue laxatives, defined as 1/2 sachet Picolax (5mg Sodium Picosulphate), 2 Glycerin suppositories (4-g mould); Timepoint(s): Daily
10. Toleration of enteral feeds (assessment of % of patients achieving full target enteral feeding); Timepoint(s): Daily
11. Gastric Residual Volume (measured every 4 hours and totalled over 24 hours); Timepoint(s): Daily

Overall trial start date

01/03/2015

Overall trial end date

28/02/2017

Reason abandoned

Eligibility

Participant inclusion criteria

1. Males and females at least 18 years of age
2. Following ICU admission, sedated with opioids and requiring invasive ventilator support
3. Scheduled for continuous infusion/administration of opioid analgesics for at least a further 24 hours
4. Constipated (not opened bowels for a minimum 48 hours following ICU admission)
5. Access for enteral administration of medications and nasogastric tube feeds
6. Initiation of nasogastric tube feeds
7. Patient weight of 38-114kg (this allows pre preparation of drug with either 8mg or 12mg)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 84; UK Sample Size: 84; Description: 84 patients across the three General Intensive Care Units within Imperial College Healthcare NHS Trust.

Participant exclusion criteria

1.Known to be pregnant
2. Patients with end stage renal failure requiring dialysis on admission
3. Diarrhoea on admission
4. Abdominal surgery within 8 weeks prior to ICU admission
5. Presence of Ileostomy or colostomy
6. Mechanical gastrointestinal obstruction
7. Suspected Acute surgical abdomen
8. History of Crohn's disease or ulcerative colitis
9. On Palliative care or not expected to survive more than 12 hours
10. Severe chronic hepatic impairment (Child Pugh Class C)
11. Suspected hepatic encephalopathy
12. Known to have received another IMP within 30 days or currently in another interventional trial that might interact with the study drug or previously enrolled into MOTION

Recruitment start date

01/09/2015

Recruitment end date

31/08/2016

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Imperial College of Science, Technology and Medicine
ICCH Building 59 North Wharf Road
London
W2 1LA
United Kingdom

Sponsor information

Organisation

Imperial College London

Sponsor details

Joint Research Compliance Office
Charing Cross Hospital
Fulham Palace Road
London
W6 8RF
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Plan to publish study protocol by September 2015. Plan to publish main study results in June 2017.

Intention to publish date

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes