Methylnaltrexone for the treatment of opioid induced constipation
| ISRCTN | ISRCTN75305839 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN75305839 |
| EudraCT/CTIS number | 2014-004687-37 |
| ClinicalTrials.gov number | NCT00672477 |
| Secondary identifying numbers | 18502 |
- Submission date
- 25/03/2015
- Registration date
- 25/03/2015
- Last edited
- 25/04/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Digestive System
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
Contact information
Scientific
Imperial College of Science, Technology and Medicine
ICCH Building
59 North Wharf Road
London
W2 1LA
United Kingdom
 ORCID ID |
0000-0001-8346-3382 |
|---|
Study information
| Study design | Randomised; Interventional; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a patient information sheet |
| Scientific title | Use of methylnaltrexone for the treatment of opioid induced constipation & gastroIntestinal stasis in intensive care patients |
| Study 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(s) | NRES Committee London - Harrow, 30/12/2014, ref: 14/LO/2004 |
| 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | Methylnaltrexone |
| Primary outcome measure | Time to significant rescue-free laxation (stool volume of greater than 100 ml) 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, 250 mg Erythromycin qds); Timepoint(s): Daily 9. Requirement of rescue laxatives, defined as 1/2 sachet Picolax (5 mg 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 study start date | 01/03/2015 |
| Overall study end date | 28/02/2018 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | 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. |
| Total final enrolment | 84 |
| 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 38-114 kg (this allows pre preparation of drug with either 8 mg or 12 mg) |
| 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 | 15/07/2017 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
59 North Wharf Road
London
W2 1LA
United Kingdom
Sponsor information
Hospital/treatment centre
Joint Research Compliance Office
Charing Cross Hospital
Fulham Palace Road
London
W6 8RF
England
United Kingdom
"ROR" |
https://ror.org/041kmwe10 |
|---|
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/12/2018 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Plan to publish study protocol by September 2015. Plan to publish main study results in December 2018. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Dr Parind Patel (p.patel@imperial.ac.uk/parind.patel@nhs.net). |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 13/07/2016 | Yes | No | |
| Basic results | 29/05/2018 | 08/06/2018 | No | No | |
| Basic results | 21/04/2019 | No | No | ||
| Basic results | 23/07/2019 | No | No | ||
| Other publications | post-hoc analysis | 01/11/2016 | 23/07/2019 | Yes | No |
| Results article | 03/02/2020 | 25/04/2023 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Additional files
- ISRCTN75305839_BasicResults_29May18.pdf
- Uploaded 08/06/2018
Editorial Notes
25/04/2023: Publication reference added.
21/04/2020: The following changes were made to the trial record:
1. Added clinicaltrialsregister.eu link to basic results (scientific).
2. The total final enrollment was added.
23/07/2019: The following changes were made to the trial record:
1. ClinicalTrials.gov number added.
2. Link to results added to basic results (scientific) field.
3. Publication reference added.
08/06/2018: Publication reference and IPD sharing statement added. The basic results of this trial have been uploaded as an additional file.
12/02/2018: The recruitment end date was changed from 31/08/2016 to 15/07/2017. Intention to publish date was added.
07/02/2018: The overall trial end date was changed from 28/02/2017 to 28/02/2018.
