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 February 2018
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
Miss Aisha Anjum
Miss Aisha Anjum
Imperial College of Science
Technology and Medicine
59 North Wharf Road
Use of methylnaltrexone for the treatment of opioid induced constipation & gastroIntestinal stasis in intensive care patients
The aim of this study is to investigate whether the drug methylnaltrexone alleviates constipation caused by opioid drugs for critical care patients.
NRES Committee London - Harrow, 30/12/2014, ref: 14/LO/2004
Randomised; Interventional; Design type: Treatment
Primary study design
Secondary study design
Randomised controlled trial
Patient information sheet
Not available in web format, please use contact details to request a patient information sheet
Topic: Critical care; Subtopic: Critical care; Disease: All Critical care
Methylnaltrexone (Relistor): Opioid antagonist
Placebo: Normal Saline
Study Entry : Registration and One or More Randomisations
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
Overall trial end date
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)
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
Recruitment end date
Countries of recruitment
Trial participating centre
Imperial College of Science, Technology and Medicine
ICCH Building 59 North Wharf Road
National Institute for Health Research
Funding Body Type
Funding Body Subtype
Results and Publications
Publication and dissemination plan
Plan to publish study protocol by September 2015. Plan to publish main study results in December 2018.
Intention to publish date
Participant level data
Available on request
Results - basic reporting