AzTrials
AzTrials

ConstipationRILAXNCT01955213

Methylnaltrexone for Opioid Induced Constipation

An observational study of Constipation, run by Amsterdam UMC, location VUmc at 6 sites in Netherlands.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

Methylnaltrexone for the treatment of opioid-induced constipation in the setting of palliative or hospice care, is significantly more effective than placebo (1). However, in both the randomized and the open-label phase of the multi center trial showing this favorable outcome, the drug produced rescue-free laxation in… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Constipation
What is being tested?
methylnaltrexone
Type of treatment
Injection or infusion
How many people
7 participants
Where
6 sitesNetherlands
Study dates
Jul 2012to Sep 2017
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Patients receiving palliative care who are being treated with opioids for symptoms of pain or dyspnea, suffering from constipation, that is not relieved by first line oral laxatives.

Who may be able to join

  • Age ≥ 18 years
  • Receiving palliative care
  • Life expectancy ≥ 2 weeks
  • Able to give informed consent
  • Receiving opioid treatment with either morphine sulphate, oxycodone or fentanyl
  • Opioid treatment, both
Show all 16Show fewer
  • 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
  • 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. If rescue medication is prescribed of a different type of opioid than the regular dosed opioid, the rescue medication should be switched to the same type as the regular dosed opioid for at least 3 days before the first dose of methylnaltrexone.
  • Has diagnosis of constipation, defined as either
  • < 3 bowel movements during the previous week by history and no clinically notable laxation* in the 24 hours before the first dose of methylnaltrexone, or
  • No clinically notable laxation* in the 48 hours before the first dose of methylnaltrexone.
  • Constipation is defined as opioid induced, determined by investigator
  • On stable laxative regimen for ≥ 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.
  • If the subject is a woman with presumed child bearing potential; negative urine pregnancy test at screening
  • 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

Who cannot join

  • Previous treatment with methylnaltrexone
  • Known or suspected mechanical gastrointestinal obstruction
  • Presence of an other cause of bowel dysfunction that is considered to be a major contribution to the constipation according to investigator
  • Presence of a peritoneal catheter for intraperitoneal chemotherapy or dialysis
  • Clinically relevant active diverticular disease
  • History of bowel surgery within 10 days before first dose of methylnaltrexone
Show all 17Show fewer
  • Fecal ostomy
  • Use of vinca alkaloids within previous 4 months
  • Body weight <38 kg
  • Renal failure defined as EGFR <30 ml/min per 1.73m2 or requires dialysis.
  • Known or suspected allergy to methylnaltrexone or similar compounds (e.g. naltrexone or naloxone)
  • Participation in a study with investigational products within 30 days before first dose of methylnaltrexone.
  • Pregnant or nursing
  • 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:
  • Chemotherapy or treatment with tyrosine kinase inhibitor during 4 weeks before inclusion or treatment scheduled during participation in this study.
  • 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.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

Netherlands6 sites

  • Medical Center Alkmaar

    Alkmaar

  • VU University Medical Center

    Amsterdam, 1081HV

  • Hospice Demeter

    De Bilt

  • Hospice Bardo

    Hoofddorp

  • Spaarne Ziekehuis

    Hoofddorp

  • University Medical Center Utrecht

    Utrecht

Other trials in Netherlands

About this study

Official title: 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

Methylnaltrexone for the treatment of opioid-induced constipation in the setting of palliative or hospice care, is significantly more effective than placebo (1). However, in both the randomized and the open-label phase of the multi center trial showing this favorable outcome, the drug produced rescue-free laxation in only about half of the patients (2). There may be several reasons for this result, since constipation in palliative care patients often has multiple simultaneously occurring causes.

Assuming that constipation of the non-responders is still opioid-induced, one of the possible reasons for not responding to methylnaltrexone could be that central actions of opioids contribute to constipation by reducing motility of the intestines through direct actions in the spinal dorsal horn (2). However, as methylnaltrexone is a µ-receptor antagonist and not all opioids are solely µ-receptor agonists another reason may well be that successful laxation is determined by the receptor-profile of the specific opioid the patient is using.

Opioids do not only influence bowel functioning, but also immune system functioning and angiogenesis. Methylnaltrexone possibly antagonizes these changes, therefore this study will also investigate the influence of methylnaltrexone on immunologic and angiogenic parameters.

Conditions
Constipation
Being tested
methylnaltrexone
Keywords
constipation, methylnaltrexone, opoid
Medical subject headings
Constipation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • methylnaltrexoneDrug

    Patients will be treated with methylnaltrexone in a standard dosing regimen for their weight: 38-62kg:8 mg, 62-114kg:12 mg, >114 kg: 0.15 mg/kg) Methylnaltrexone will be administered subcutaneously every other day for up to 7 doses.

Study groups in NCT01955213
Study groupRoleWhat they receive
Morphine SulphatePatient groups are defined by the type of opioid used, being either morphine sulphate, fentanyl or oxycodone.Patients will be treated with methylnaltrexone in a standard dosing regimen for their weight: 38-62kg:8 mg, 62-114kg:12 mg, >114 kg: 0.15 mg/kg) Methylnaltrexone will be administered subcutaneously every other day for up to 7 doses.
Receives: Drug: methylnaltrexone
FentanylPatient groups are defined by the type of opioid used, being either morphine sulphate, fentanyl or oxycodone.Patients will be treated with methylnaltrexone in a standard dosing regimen for their weight: 38-62kg:8 mg, 62-114kg:12 mg, >114 kg: 0.15 mg/kg) Methylnaltrexone will be administered subcutaneously every other day for up to 7 doses.
Receives: Drug: methylnaltrexone
OxycodonePatient groups are defined by the type of opioid used, being either morphine sulphate, fentanyl or oxycodone.Patients will be treated with methylnaltrexone in a standard dosing regimen for their weight: 38-62kg:8 mg, 62-114kg:12 mg, >114 kg: 0.15 mg/kg) Methylnaltrexone will be administered subcutaneously every other day for up to 7 doses.
Receives: Drug: methylnaltrexone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rescue-free laxation response

    The 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).

    Measured: Within 4 hours after at least 2 of the first 4 doses (the first week of treatment).

Secondary outcomes (6)

  1. Time to first laxation

    Time to first laxation after initiation of treatment

    Measured: Between dosing and day 14

  2. Number of laxations

    • Number of laxations per week
    • Change in BFI score between day 0 and 14

    Measured: Between dosing and day 14

  3. Laxation within 4 hours

    Presence of laxation within four hours after initiation of treatment

    Measured: Between dosing and day 14

  4. laxation within 4 hours after each dose

    Number of doses after which laxation occured within four hours after treatment administration

    Measured: Between dosing and day 14

  5. laxation within 24 hours after each dose

    Number of doses after which laxation occured within 24 hours after treatment administration

    Measured: Between dosing and day 14

  6. laxation within 4 hours after 4 out of 7 doses

    Did laxation occur within 4 hours after at least 4 out of 7 treatment administrations?

    Measured: Between dosing and day 14

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Oct 2013 (estimated)
  2. Study startJul 2012
  3. Primary completionSep 2017
  4. Study completionSep 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case-control
Time perspective
Prospective
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01955213
Sponsor's protocol ID
2012/169
Other IDs
2012-000850-75
Acronym
RILAX
Status last verified
Jul 2019
First submitted
11 Dec 2012
Last updated
5 Aug 2019
Results posted
No
Data monitoring committee
No

Publications

  • Neefjes ECW, van der Wijngaart H, van der Vorst MJDL, Ten Oever D, van der Vliet HJ, Beeker A, Rhodius CA, van den Berg HP, Berkhof J, Verheul HMW. Optimal treatment of opioid induced constipation in daily clinical practice - an observational study. BMC Palliat Care. 2019 Mar 29;18(1):31. doi: 10.1186/s12904-019-0416-7.

    PubMed 30922276

  • Neefjes EC, van der Vorst MJ, Boddaert MS, Zuurmond WW, van der Vliet HJ, Beeker A, van den Berg HP, van Groeningen CJ, Vrijaldenhoven S, Verheul HM. 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. BMC Palliat Care. 2014 Aug 20;13:42. doi: 10.1186/1472-684X-13-42. eCollection 2014.

    PubMed 25165428

Questions about this trial

What is this clinical trial studying?

An observational study of Constipation, run by Amsterdam UMC, location VUmc at 6 sites in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 5 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study was stopped early. Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rescue-free laxation response (time frame: Within 4 hours after at least 2 of the first 4 doses (the first week of treatment).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01955213, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in