National Horizon Scanning Centre. Methylnaltrexone (MOA-728) for postoperative ileus. April 2008

Transcription

1 (MOA-728) for postoperative ileus April 2008 This technology summary is based on information available at the time of research and a limited literature search. It is not intended to be a definitive statement on the safety, efficacy or effectiveness of the health technology covered and should not be used for commercial purposes. The Research Programme is part of the National Institute for Health Research

2 (MOA-728) for postoperative ileus Target group Postoperative ileus (POI). Background Postoperative ileus is a temporary impairment of gastrointestinal motility that commonly occurs after major abdominal surgery. It can also occur following chest, pelvic and orthopaedic surgery. It is characterised by bloating, vomiting, constipation, cramps and loss of appetite. In most cases it resolves spontaneously in 2-3 days. Endogenous and exogenous opioids have been implicated in the development and exacerbation of POI. POI can cause a delay in postoperative recovery and consequently increase length of stay in. Technology description (MNTX, MOA-728, bromide) is an intravenous (IV) selective peripheral opioid receptor antagonist. The dosage has yet to be confirmed, but in one trial it was given at 0.3 mg/kg every as a subcutaneous (SC) formulation is pre-registration for opioidinduced constipation in the EU. Innovation and/or advantages is in a new drug class and may have the potential to reduce the length of postoperative stay for a significant number of patients. Developer Progenics/Wyeth Pharmaceuticals. Availability, launch or marketing dates, and licensing plans: In phase III clinical trials. NHS or Government priority area: No NHS priority area was identified. Clinical need and burden of disease Estimating the annual number of POI cases is difficult. In the year 2005/6 there were approximately 21,000 admissions for segmental colectomies and approximately 5,000 admissions for ventral hernia operations a. The proportion of abdominal surgery patients who receive opioids for post-operative pain relief is unknown. Existing comparators and treatments Strategies to reduce the risk of POI and to restore bowel motility include: Nasogastric tubes for gastric decompression Early postoperative feeding Local anaesthesia and epidurals a Segmental colectomies: OPCS codes H04.1-H11.9,H12.2 and H /Ventral hernia operations: OPCS codes T27.1 T

3 Efficacy and safety Trial name MNTX 203 Phase II NCT Phase III 1 NCT Phase III 2 NCT Phase III 3 Sponsor Progenics Wyeth Progenics Wyeth Progenics Status Conference Completed Ongoing Ongoing abstract 4 Location US Worldwide Worldwide Worldwide Design Participants n= 65; segmental colectomies. Received IV methylnaltrexone 0.3 mg/kg every 6 hours. Follow-up Approximately 6 Primary outcome Time to tolerance of solid food, time Secondary to first bowel outcomes movement, time to discharge eligibility, time to discharge. Key results vs. - Toleration of full liquids: 70 ± 9 vs. 100 ± 19 hrs (p=0.05); toleration of solid foods: 100 ± 11 vs. 125 ± 17 hrs (p=0.12); first bowel movement: 97 ± 6 vs. 120 ± 10 hrs (p=0.01); discharge eligibility: 119 ± n= 495; adults; segmental colectomy via open laparotomy with general anaesthesia. IV every Approximately 6 Time to first bowel movement. Time to discharge eligibility, time to discharge, nausea, retching/vomiting, patient global satisfaction with treatment, patient abdominal pain VAS; EQ-5D, opioid-related symptom distress n= 495 (planned); adults; segmental colectomy; receiving opioids for post-operative pain relief. IV every n= 500 (planned); adults; ventral wall hernia repair with general anaesthesia. IV every 6 Approximately 6 Time to first Time to first bowel movement. bowel movement. Time to discharge Time to discharge eligibility, time to eligibility, time to discharge, nausea, discharge, nausea, retching/vomiting, retching/vomiting, patient global patient global satisfaction with satisfaction with treatment, patient treatment, patient abdominal pain abdominal pain VAS; EQ-5D, VAS; EQ-5D, opioid-related opioid-related symptom distress symptom distress

4 Expected reporting date Adverse effects 7 vs. 149 ± 17 hrs (p=0.03); actual discharge: 140 ± 6 vs. 165 ± 16 hrs (p=0.09). - Q Q Q The most common adverse events were fever and nausea Estimated cost and cost impact The cost of methylnaltrexone is yet to be determined. There may be additional costs associated with intravenous administration, although post-operative patients are likely to be receiving other concomitant intravenous medications. These costs may be offset by a reduction in the length of stay and associated complications. Potential or intended impact speculative Patients Reduced morbidity Quicker, earlier or more accurate diagnosis or identification of disease Reduced mortality or increased survival Other: Improved quality of life for patients and/or carers None identified Services Increased use Service reorganisation required Staff or training required Decreased use: possible reduction in length of stay. Other: None identified Costs Increased unit cost compared to Increased costs: more patients Increased costs: capital alternative coming for treatment investment needed New costs: Savings: Other: References 1 Clinicaltrials.gov. Study Evaluating IV methylnaltrexone for the treatment of post operative ileus. accessed 17/01/ Clinicaltrials.gov. Study of intravenous (IV) methylnaltrexone bromide (MNTX) in the treatment of post operative ileus (POI). accessed 17/01/ Clinicaltrials.gov. A study evaluating IV MOA-728 for the treatment of POI in subjects after ventral hernia repair. accessed 17/01/ Viscusi, E., Rathmell, J., Fichera., A. et al. A double blind, randomised, controlled trial of methylnaltrexone (MNTX) for post-operative bowel dysfunction in segmental colectomy patients. American Society of Anesthesiologists 2005; 103: A893. 4

5 The National Institute for Health Research Research Programme is funded by the Department of Health. The views expressed in this publication are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health The, Department of Public Health and Epidemiology University of Birmingham, Edgbaston, Birmingham, B15 2TT, England Tel: +44 (0) Fax +44 (0)