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Clinical evaluation of the efficacy of methylnaltrexone in resolving constipation induced by different opioid subtypes combined with laboratory analysis of immunomodulatory and antiangiogenic effects of methylnaltrexone


- candidate number15735
- NTR NumberNTR4272
- ISRCTNISRCTN wordt niet meer aangevraagd.
- Date ISRCTN created
- date ISRCTN requested
- Date Registered NTR20-nov-2013
- Secondary IDs2012/169  METC VUmc
- Public TitleClinical evaluation of the efficacy of methylnaltrexone in resolving constipation induced by different opioid subtypes combined with laboratory analysis of immunomodulatory and antiangiogenic effects of methylnaltrexone
- Scientific TitleClinical evaluation of the efficacy of methylnaltrexone in resolving constipation induced by different opioid subtypes combined with laboratory analysis of immunomodulatory and antiangiogenic effects of methylnaltrexone
- ACRONYMMethylnaltrexone for opioid induced constipation
- hypothesisthe efficacy of methylnaltrexone differs between different opioid subtypes
- Healt Condition(s) or Problem(s) studiedConstipation, Obstipation, Opioids
- Inclusion criteria. Age >/= 18 years 2. Receiving palliative care 3. Life expectancy > 2 weeks 4. Able to give informed consent 5. Receiving opioid treatment with either morphine sulphate, oxycodone or fentanyl 6. Opioid treatment, both a) On a regular schedule (not just as needed or rescue doses) for the control of pain or dyspnea for at least 2 weeks before the first dose of methylnaltrexone, and b) On a stable opioid regimen for at least 3 days before the first dose of methylnaltrexone. This is defined as no dose reduction of >/= 50%, dose increases are permitted. 7. If a subject uses a combination of short- and long-acting (including continuous administration) opioids, the short-acting opioid should preferably be of the same type as the long-acting opioid. If the subject uses a different type of short-acting opioid than the long-acting opioid, the subject is allowed to enter the study if he/she has used this short-acting opioid /= 3 days before the first dose of methylnaltrexone. This is defined as at least one type of laxative in an adequate dosing regimen, (e.g. macrogol 2 packets daily, magnesium(hydr)oxide 500 mg three times daily, bisacodyl 10 mg daily or sennoside A+B 10 ml daily) or at least two types of laxatives in a suboptimal dose with patient characteristics hampering optimal treatment. 11. If the subject is a woman with presumed child bearing potential; negative urine pregnancy test at screening 12. Surgically sterile or agrees to use a medically acceptable method of birth control or practice sexual abstinence for the duration of the methylnaltrexone treatment and the following 15 days. ~ * including laxation after rescue laxative or enema ~ not necessary for postmenopausal women
- Exclusion criteria1. Previous treatment with methylnaltrexone 2. Known or suspected mechanical gastrointestinal obstruction 3. Presence of an other cause of bowel dysfunction that is considered to be a major contribution to the constipation according to investigator 4. Presence of a peritoneal catheter for intraperitoneal chemotherapy or dialysis 5. Clinically relevant active diverticular disease 6. History of bowel surgery within 10 days before first dose of methylnaltrexone 7. Fecal ostomy 8. Use of vinca alkaloids within previous 4 months 9. Body weight <38 kg 10. Renal failure defined as EGFR <30 ml/min per 1.73m2 or requires dialysis. 11. Known or suspected allergy to methylnaltrexone or similar compounds (e.g. naltrexone or naloxone) 12. Participation in a study with investigational products within 30 days before first dose of methylnaltrexone. 13. Pregnant or nursing 14. Clinically important abnormalities that may interfere with participation or compliance to the study, determined by investigator Additional exclusion criteria for the immunologic and angiogenic analysis part of the study: 15. Chemotherapy or treatment with tyrosine kinase inhibitor during 4 weeks before inclusion or treatment scheduled during participation in this study. 16. Treatment with high dose corticosteroids during 2 weeks before inclusion in this study. This is defined as the equivalent of 30 mg of prednisone per day for >/= 2 consecutive days.
- mec approval receivedyes
- multicenter trialyes
- randomisedno
- groupParallel
- Type[default]
- Studytypeobservational
- planned startdate 25-jul-2012
- planned closingdate1-mrt-2014
- Target number of participants195
- InterventionsThe three study groups (morphine sulphate, oxycodon and fentanyl) will all receive treatment with methylnaltrexone every other day for 14 days (7 doses).
- Primary outcomeThe proportion of subjects that has a rescue-free laxation response within 4 hours after at least 2 of the first 4 doses (the first week of treatment).
- Secondary outcome- Time to first laxation
- Laxation within 4 hours after the first dose of study drug
- Laxation within 4 or 24 hours after each dose
- Laxation within 4 hours after at least 4 of the maximum 7 doses
- Number of laxations per week
- Change in BFI score between day 0 and 14
- changes in immunologic and angiogenic markers
- Timepointsrespons after methylnaltrexone administration day 0 to 14
BFI day 0 and 14
laboratory part day 0, 1, 14 and 42
- Trial web siteN/A
- statusopen: patient inclusion
- CONTACT FOR PUBLIC QUERIESProf. dr. H.M.W. Verheul
- CONTACT for SCIENTIFIC QUERIESProf. dr. H.M.W. Verheul
- Sponsor/Initiator VU University Medical Center
- Funding
(Source(s) of Monetary or Material Support)
Fonds Nuts-Ohra
- PublicationsN/A
- Brief summaryOpioid-induced constipation (OIC) is one of the major problems in palliative care with a prevalence of 10-50%. Methylnaltrexone for the treatment of OIC is significantly more effective than placebo, but it produces rescue-free laxation only in about fifty percent of the patients regardless of the dose. Because methylnaltrexone is a -receptor antagonist and not all opioids are solely -receptor agonists, it is likely that the effect of methylnaltrexone is mainly determined by the receptor-profile of each specific opioid. Besides its effect on OIC, methylnaltrexone has also been shown to reduce opioid-induced changes in immune system functioning and angiogenesis in pre-clinical studies. In this multi-center, prospective, parallel group trial we will evaluate the efficacy of methylnaltrexone in resolving OIC in the most common opioid subtypes: morphine, oxycodone and fentanyl. In total 195 patients with OIC, despite prophylactic laxatives, are prescribed methylnaltrexone every other day up to fourteen days. Participants will report its effect in a laxation diary. Group allocation is based on the opioid type the participant is using. At the start and end of the study period, participants complete the Bowel Function Index questionnaire. A subgroup is invited to donate blood for analysis of immunomodulatory and anti-angiogenic effects of methylnaltrexone.
- Main changes (audit trail)
- RECORD20-nov-2013 - 6-dec-2013


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