Constipation, Opioid-InducedPhase 4OMAMANCT05216328
Prevention of Opioid-induced Constipation in Patients With Advanced Cancer
A Phase 4 study testing Macrogol Only Product in Oral Dose Form and Magnesium hydroxide 724mg in people with Constipation, Opioid-Induced, run by Amsterdam UMC, location VUmc at 13 sites in Netherlands.
Trial summary
More than 70% of patients with cancer in the palliative phase have pain that often requires treatment with opioids (morphine-like agents). Constipation occurs in 59% of patients treated with opioids. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Constipation, Opioid-Induced
- What is being tested?
- Macrogol Only Product in Oral Dose Form and Magnesium hydroxide 724mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 258 participants
- Where
- 13 sitesNetherlands
- Study dates
- 2 Dec 2022to Jun 2027
- Phase
- Phase 4
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
Who may be able to join
- In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- Patients with advanced cancer (≥18 years);
- Starting with slow release or transdermal opioids for pain;
- Able to complete a Dutch questionnaire. Previous treatment with opioids is allowed, if discontinued more than 4 weeks ago.
Who cannot join
- A potential subject who meets any of the following criteria will be excluded from participation in this study:
- Patients with contra-indications for laxatives
- Maintenance treatment with laxatives during the last 14 days
- Severely impaired renal function (serum creatinine >180 umol/l)
- Estimated life expectancy <1 month
Trial locations and contacts
13 sites in 1 country. Contact the study team or a site near you to ask about taking part.
13 sites in 1 country
Netherlands13 sites, 13 recruiting
- Recruiting
Jeroen Bosch Ziekenhuis
's-Hertogenbosch, North Brabant, 5223 GZ
Tineke Smilde, Dr., t.smilde@jbz.nl
- Recruiting
Flevoziekenhuis
Almere Stad, Flevoland, 1315 RA
Dirkje Sommeijer, Dr., dsommeijer@flevoziekenhuis.nl
- Recruiting
Amsterdam UMC, location VUmc
Amsterdam, North Holland, 1081 HV
Monique Steegers, Prof. dr., +31 (0)20 444 4444, m.steegers@amsterdamumc.nl
- Recruiting
Rijnstate Ziekenhuis
Arnhem, Gelderland, 6815 AD
Maurice van der Vorst, Drs., mvandervorst@rijnstate.nl
- Recruiting
Groene Hart Hospital
Gouda, South Holland, 2803 HH
Marissa Cloos-van Balen, MD, Marissa.Cloos@ghz.nl
- Recruiting
University Medical Center Groningen
Groningen, Provincie Groningen, 9713 GZ
AN Reyners, Prof. dr., +31 50 361 28 21, a.k.l.reyners@umcg.nl
- Recruiting
Martini Hospital Groningen
Groningen, Provincie Groningen, 9728 NT
Annette van der Velden, Dr., a.vandervelden@mzh.nl
- Recruiting
Spaarne Gasthuis
Hoofddorp, North Holland, 2134 TM
Gerty de Klerk, Drs., g.deklerk@spaarnegasthuis.nl
- Recruiting
Leiden University Medical Center
Leiden, South Holland, 2333 ZA
Marije Slingerland, Dr., m.slingerland@lumc.nl
- Recruiting
Radboud university Medical center Nijmegen
Nijmegen, Gelderland, 6525 GA
Kris Vissers, Prof. dr, +31-24-3666353, Kris.Vissers@radboudumc.nl
Evelien Kuip, Dr., +31-24-36592857, Evelien.Kuip@radboudumc.nl
- Recruiting
Erasmus Medical Center
Rotterdam, South Holland, 3015 GD
Karin van der Rijt, Prof. dr., c.vanderrijt@erasmusmc.nl
- Recruiting
Haaglanden Medical Centre
The Hague, South Holland, 2512 VA
Anouk Jochems, MD, a.jochems@haaglandenmc.nl
- Recruiting
University Medical Center Utrecht
Utrecht, Utrecht, 3584 CX
Filip de Vos, Dr., +31-88-7556265, f.devos@umcutrecht.nl
Alexander de Graeff, Dr., +31-88-7556308, A.deGraeff-2@umcutrecht.nl
About this study
Official title: OMAMA-study - Prevention of Opioid-induced Constipation in Patients With Advanced Cancer
More than 70% of patients with cancer in the palliative phase have pain that often requires treatment with opioids (morphine-like agents). Constipation occurs in 59% of patients treated with opioids. Opioid-induced constipation (OIC) has consequences that range from daily discomfort with social insecurity and disability to intestinal obstruction. It leads to limitations in self-management, a reduced quality of life and a risk of the need for more care. In the guideline "Diagnosis and treatment of pain in patients with cancer" it is recommended to start preventively with an osmotic laxative such as macrogol/electrolytes or magnesium hydroxide when starting opioids. Macrogol/electrolytes has been proven to be effective for OIC, but is sometimes perceived by patients as unpleasant due to its taste. Magnesium hydroxide, which is less commonly prescribed for OIC, has a neutral taste. Although it is mentioned in the guideline, it is not studied for the treatment of OIC and also not officially registered for this. To support the advice of the guideline and to prove that a choice is possible, it is important to investigate whether there are differences in effectiveness and/or side effects between macrogol/electrolytes and magnesium hydroxide in the prevention of OIC.
The aim of this study is to compare macrogol/electrolytes with magnesium hydroxide in the prevention of opioid-induced constipation in patients with cancer in the palliative (incurable) phase, who start opioids because of pain. The choice of laxative is determined by drawing lots (randomisation). After two weeks, its effect will be assessed and will be presented as the percentage of patients who have not developed constipation after starting opioids. If the laxative, as assigned by lot, is described as satisfactory by the patient, the patient can continue with the drug that the patient used, after the study through regular prescription.
The investigators will ask the patients in the study about their satisfaction with the laxative used, any side effects and the degree of pain. Furthermore, the appeal to care for possible constipation will be examined. Because the best attainable quality of life in the palliative phase is the objective of all care, the investigators will also measure this perceived quality with a questionnaire in this study. The results of this study will lead to the best achievable prevention of opioid constipation in patients with cancer in the palliative phase.
- Conditions
- Constipation, Opioid-Induced
- Being tested
- Macrogol Only Product in Oral Dose Form, Magnesium hydroxide 724mg
- Keywords
- Cancer, Palliative care, Cancer pain, Opioid-Induced Constipation, macrogol/electrolytes, magnesium hydroxide
- Medical subject headings
- Opioid-Induced Constipation, Neoplasms, Cancer Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Macrogol Only Product in Oral Dose FormDrug
Also called Macrogol/electrolytes
Information already included in arm/group description.
Magnesium hydroxide 724mgDrug
Also called Magnesiumoxide
Information already included in arm/group description.
| Study group | Role | What they receive |
|---|---|---|
| Macrogol/electrolytes | Active comparator | Macrogol/electrolytes is started at a dose of 1 sachet once a day orally, based on the current guideline 'Diagnosis and treatment of pain in patients with cancer' (www.pallialine.nl). The dose of macrogol/electrolytes may be increased to 2 sachets a day during the study period.
The effect of laxatives will be judged after 14 days. Receives: Drug: Macrogol Only Product in Oral Dose Form |
| Magnesium hydroxide | Active comparator | Magnesium hydroxide is started at a dose of 724 mg three times a day orally, based on the current guideline 'Diagnosis and treatment of pain in patients with cancer' (www.pallialine.nl). The dose of magnesium hydroxide may be increased to 1448 mg three times a day during the study period. The effect of laxatives will be judged after 14 days. Receives: Drug: Magnesium hydroxide 724mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
The percentage of patients with a score of <30 of the Bowel Function Index
A clinician-administered patient-reported questionnaire to assess clinically significant constipation, validated in patients receiving opioids for chronic non-malignant pain and for malignant pain (Abramovitz 2013, Rentz 2009 and 2011). It consists of three questions, assessing ease of defecation, feeling of incomplete bowel evacuation and personal judgement of the patient regarding constipation, each during the last 7 days and each rated on a scale of 0 (best possible outcome) to 100 (worst possible outcome). A total score ≥30 (mean of the three separate scores) indicates clinically significant constipation. A change of the total score of >12 is regarded as clinically meaningful. It has been used in a large observational study in cancer patients receiving opioids (Davies 2021) and in randomised trials of opioid antagonists for OIC (Ahmedzai 2012, Dupoiron 2017, Leng 2020, Poelaert 2015). It has been recommended as the assessment tool of choice for OIC (Argoff 2015, Farmer 2019).
Measured: On day 14
Secondary outcomes (6)
The EQ5D
A self-administered, generic assessment tool developed by the EuroQol Group, a network of international research teams, and consists of questions on five dimensions of health (i.e., mobility, self-care, pain/discomfort, usual activities, and anxiety/depression) (Pickard 2007). It has been used in cost-effectiveness studies on OIC (Dunlop 2012, Hjalte 2016, Lawson 2016).
Measured: On day 0 and day 14
Rome IV criteria for opioid-induced constipation
Rome IV criteria for opioid-induced constipation as judged by professional care givers (Davies 2021, Drossman 2016), including:
- straining during >25% of defecations
- lumpy or hard stools in >25% of defecations
- sensation of incomplete evacuation in >25% of defecations
- sensation of anorectal obstruction/blockage in >25% of defecations
- manual manoeuvres to facilitate >25% of defecations
- <3 spontaneous defecations per week At least two of these criteria have to be fulfilled in order to diagnose constipation, to be judged by the treating physician or clinical nurse specialists/nurse practitioners
Measured: On day 0 and day 14
Cancer pain score
Numeric Rating SDcale, ranging from 0 to 10
Measured: On day 0 and day 14
Patient satisfaction with laxative
A single four-item question, ranging from unsatisfied to very satisfied.
Measured: On day 14
Side effects of laxatives
All side-effects are scored on a four-point Likert scale (not at all, a bit, rather, very much):
- Bad taste
- Problems with swallowing
- Abdominal cramps
- Nausea
- Flatulence
- Diarrhea
- Other (to be specified by the patient)
Measured: On day 14
Cost-effectiveness of macrogol/electrolytes compared to magnesium hydroxide
We aim to perform a comparative cost-effectiveness of the laxatives. This requires data collection on healthcare procedures and QOL in responders, non-responders and patients with side-effects of laxatives for the follow-up period of the study. These healthcare procedures will be extracted from hospital databases and healthcare use outside the hospital will be collected with the iMCQ at 4 weeks. All individual health care procedures will be linked to their unit costs. Reimbursement prices issued by the Dutch Healthcare Authority and national reference prices will be used for this assessment as outlined in current Dutch pharmaco-economic guidance. The cost-effectiveness analysis will be performed using a decision tree including different branches for initial therapy and responders and non-responders. The costs and QOL of the patients in the trial will be used as input for this decision tree. Total costs and effects will be calculated by summing the costs and effects of each branch.
Measured: On day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2022
- Study start2 Dec 2022
- Primary completionJan 2027 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (28)Papers the sponsor has linked to this study.
- Other trials for Constipation, Opioid-InducedStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 258 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Collaborators
- Leiden University Medical Center, University Medical Center Groningen, Radboud University Medical Center, Erasmus Medical Center, Spaarne Gasthuis, Rijnstate Hospital, Jeroen Bosch Ziekenhuis, Flevoziekenhuis, Martini Hospital Groningen, Haaglanden Medical Centre, UMC Utrecht, Groene Hart Ziekenhuis, Bernhoven Hospital, Isala, Antoni van Leeuwenhoek Hospital
- Responsible party
- Principal investigator, Lia van Zuylen, Amsterdam UMC, location VUmc
- Investigators
- Lia van Zuylen, Prof.dr., Principal investigator, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05216328
- Sponsor's protocol ID
- 08440012010002
- Acronym
- OMAMA
- Status last verified
- Sep 2026
- First submitted
- 19 Jan 2022
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Due to the sensitivity of the data, the underlying data sets will not be shared publicly but will be made available for verification/ inspection purposes. Additional sharing conditions will be considered (e.g. via the Personal Health Train initiative from Health-RI, which is currently under development) while respecting the type of informed consent provided by the subjects and discussed with the support of Legal/Privacy/RDM experts where appropriate. For descriptive documentation (protocol, data dictionary, syntax/script, etc.) the study team will collaborate with RDM, to ensure such data can be found and made available to other researchers. Providing information in an online (metadata) catalogue that is certified holds preference. We are considering using a DANS repository or similar. DANS EASY is commonly used, uses the Dublin Core Metadata standard, provides a PID and holds a Core Trust Seal. However, DANS is initiatiating Data Stations, with a specific one for the Life Sciences and
Publications
Abramowitz L, Beziaud N, Causse C, Chuberre B, Allaert FA, Perrot S. Further validation of the psychometric properties of the Bowel Function Index for evaluating opioid-induced constipation (OIC). J Med Econ. 2013 Dec;16(12):1434-41. doi: 10.3111/13696998.2013.851083. Epub 2013 Oct 24.
PubMed 24102611Ahmedzai SH, Nauck F, Bar-Sela G, Bosse B, Leyendecker P, Hopp M. A randomized, double-blind, active-controlled, double-dummy, parallel-group study to determine the safety and efficacy of oxycodone/naloxone prolonged-release tablets in patients with moderate/severe, chronic cancer pain. Palliat Med. 2012 Jan;26(1):50-60. doi: 10.1177/0269216311418869. Epub 2011 Sep 21.
PubMed 21937568Argoff CE, Brennan MJ, Camilleri M, Davies A, Fudin J, Galluzzi KE, Gudin J, Lembo A, Stanos SP, Webster LR. Consensus Recommendations on Initiating Prescription Therapies for Opioid-Induced Constipation. Pain Med. 2015 Dec;16(12):2324-37. doi: 10.1111/pme.12937. Epub 2015 Nov 19.
PubMed 26582720Bell T, Annunziata K, Leslie JB. Opioid-induced constipation negatively impacts pain management, productivity, and health-related quality of life: findings from the National Health and Wellness Survey. J Opioid Manag. 2009 May-Jun;5(3):137-44. doi: 10.5055/jom.2009.0014.
PubMed 19662923Christensen HN, Olsson U, From J, Breivik H. Opioid-induced constipation, use of laxatives, and health-related quality of life. Scand J Pain. 2016 Apr;11:104-110. doi: 10.1016/j.sjpain.2015.12.007. Epub 2016 Jan 25.
PubMed 28850447Davies A, Leach C, Butler C, Gregory A, Henshaw S, Minton O, Shorthose K, Batsari KM. Opioid-induced constipation in patients with cancer: a "real-world," multicentre, observational study of diagnostic criteria and clinical features. Pain. 2021 Jan;162(1):309-318. doi: 10.1097/j.pain.0000000000002024.
PubMed 32701649Dhingra L, Shuk E, Grossman B, Strada A, Wald E, Portenoy A, Knotkova H, Portenoy R. A qualitative study to explore psychological distress and illness burden associated with opioid-induced constipation in cancer patients with advanced disease. Palliat Med. 2013 May;27(5):447-56. doi: 10.1177/0269216312450358. Epub 2012 Jun 15.
PubMed 22707180Drossman DA. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features and Rome IV. Gastroenterology. 2016 Feb 19:S0016-5085(16)00223-7. doi: 10.1053/j.gastro.2016.02.032. Online ahead of print.
PubMed 27144617Dunlop W, Uhl R, Khan I, Taylor A, Barton G. Quality of life benefits and cost impact of prolonged release oxycodone/naloxone versus prolonged release oxycodone in patients with moderate-to-severe non-malignant pain and opioid-induced constipation: a UK cost-utility analysis. J Med Econ. 2012;15(3):564-75. doi: 10.3111/13696998.2012.665279. Epub 2012 Feb 23.
PubMed 22313329Dupoiron D, Stachowiak A, Loewenstein O, Ellery A, Kremers W, Bosse B, Hopp M. A phase III randomized controlled study on the efficacy and improved bowel function of prolonged-release (PR) oxycodone-naloxone (up to 160/80 mg daily) vs oxycodone PR. Eur J Pain. 2017 Oct;21(9):1528-1537. doi: 10.1002/ejp.1054. Epub 2017 Jun 22.
PubMed 28641363Farmer AD, Drewes AM, Chiarioni G, De Giorgio R, O'Brien T, Morlion B, Tack J. Pathophysiology and management of opioid-induced constipation: European expert consensus statement. United European Gastroenterol J. 2019 Feb;7(1):7-20. doi: 10.1177/2050640618818305. Epub 2018 Dec 14.
PubMed 30788113Freedman MD, Schwartz HJ, Roby R, Fleisher S. Tolerance and efficacy of polyethylene glycol 3350/electrolyte solution versus lactulose in relieving opiate induced constipation: a double-blinded placebo-controlled trial. J Clin Pharmacol. 1997 Oct;37(10):904-7. doi: 10.1002/j.1552-4604.1997.tb04264.x.
PubMed 9505981Ginex PK, Hanson BJ, LeFebvre KB, Lin Y, Moriarty KA, Maloney C, Vrabel M, Morgan RL. Management of Opioid-Induced and Non-Opioid-Related Constipation in Patients With Cancer: Systematic Review and Meta-Analysis. Oncol Nurs Forum. 2020 Nov 1;47(6):E211-E224. doi: 10.1188/20.ONF.E211-E224.
PubMed 33063777Hawley P, MacKenzie H, Gobbo M. PEG vs. sennosides for opioid-induced constipation in cancer care. Support Care Cancer. 2020 Apr;28(4):1775-1782. doi: 10.1007/s00520-019-04944-5. Epub 2019 Jul 18.
PubMed 31321524Head SJ, Kaul S, Bogers AJ, Kappetein AP. Non-inferiority study design: lessons to be learned from cardiovascular trials. Eur Heart J. 2012 Jun;33(11):1318-24. doi: 10.1093/eurheartj/ehs099. Epub 2012 May 7.
PubMed 22564354