Opioid Induced Constipation MedDRA version: 17.1 Level: PT Classification code 10010774 Term: Constipation System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Interventions
Trade Name: Relistor
Product Name: Relistor
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Methylnaltrexone bromide
CAS Number: 73232-52-7
Concentration unit: mg milligram(s)
Concent
Sponsors
Imperial College Healthcare NHS Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Males and females = 18 years of age • Following ICU admission, sedated with opioids and requiring invasive ventilator support • Scheduled for continuous infusion/administration of opioid analgesics for at least a further 24 hours • Constipated (not opened bowels for a minimum 48 hours following ICU admission) • Access for enteral administration of medications and nasal-gastric tube feeds • Initiation of nasogastric tube feeds • Patient weight of 38-114kg (this allows pre preparation of drug with either 8mg or 12mg) Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: • Known to be pregnant • Patients with end stage renal failure requiring dialysis on admission • Diarrhoea on admission • Abdominal surgery within 8 weeks prior to ICU admission • Presence of Ileostomy or colostomy • Mechanical gastrointestinal obstruction • Suspected Acute surgical abdomen • History of Crohn's disease or ulcerative colitis • On Palliative care or not expected to survive more than 12 hours • Severe chronic hepatic impairment (Child Pugh Class C) • Suspected hepatic encephalopathy • 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of methylnaltrexone in producing laxation in patients sedated with opioid infusions.;Secondary Objective: 1. To assess if the use of methylnaltrexone leads to increased opioid requirements through CNS penetration and antagonism 2. To assess if there are additional benefits from preventing constipation such as reduced gastric stasis, improved enteral feeding, and a reduction in infection 3. To assess the safety and side effect profile of intravenous methylnaltrexone in ICU patients 4. Blood will further analysed and stored for: • Cytokine levels • Leucocyte function assays • Metabolic profiles;Primary end point(s): Time to rescue-free opening bowels following randomisation. Significant bowel opening is defined as an estimate of stool volume of greater than 100nls by the attending nurse.;Timepoint(s) of evaluation of this end point: Up to 28 days after randomisation. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Gastric Residual Volume measured every 4 hours and totalled over 24 hours • Toleration of enteral feeds: Daily assessment of % of patients achieving full target enteral feeding • Requirement of rescue laxatives (1/2 sachet picolax, 2 glycerin suppositories) • Requirement of prokinetics (10mg metoclopramide tds, 250mg erythromycin qds) • Average number of bowel movements per day • Escalation of opioid dose due to antagonism/reversal of analgesia and sedation • Incidence of ventilator associated pneumonia (VAP), defined by the Clinical Pulmonary Infection Score (CPIS) • Incidence of diarrhoea • Incidence of Clostridium difficile infection: PCR or Toxin positive • Incidence of positive microbiology blood cultures • Mortality: 28 day, ICU and Hospital Secondary mechanistic Outcomes: • Sepsis Biomarkers • Leucocyte Function Tests • Leucocyte Migration Assays;Timepoint(s) of evaluation of this end point: Daily througout trial and up to 28 days after randomisation. | — |
Countries
United Kingdom
Contacts
Public ContactParind Patel
Imperial College Healthcare NHS Trust
Outcome results
None listed