OMAMA: Prevention of Opioid-induced Constipation in Patients With Metastatic Cancer

Sponsor

Amsterdam UMC, location VUmc (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05216328

Collaborator

UMC Utrecht (Other), Leiden University Medical Center (Other), University Medical Center Groningen (Other), Radboud Ziekenhuis (Other), Erasmus Medical Center (Other), Spaarne Gasthuis (Other), Ziekenhuis Rijnstate (Other), Jeroen Bosch Ziekenhuis (Other), Flevoziekenhuis (Other)

330

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief 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. 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.

Condition or Disease	Intervention/Treatment	Phase
Constipation, Opioid-Induced	Drug: Macrogol Only Product in Oral Dose Form Drug: Magnesium hydroxide 724mg	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

330 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

OMAMA-study - Prevention of Opioid-induced Constipation in Patients With Metastatic Cancer

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Aug 1, 2024

Anticipated Study Completion Date :

Oct 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Macrogol/electrolytes 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.	Drug: Macrogol Only Product in Oral Dose Form Information already included in arm/group description. Other Names: Macrogol/electrolytes
Active Comparator: Magnesium hydroxide 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.	Drug: Magnesium hydroxide 724mg Information already included in arm/group description. Other Names: Magnesiumoxide

Arm

Intervention/Treatment

Active Comparator: Macrogol/electrolytes

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.

Drug: Macrogol Only Product in Oral Dose Form

Information already included in arm/group description.

Other Names:

Macrogol/electrolytes

Active Comparator: Magnesium hydroxide

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.

Drug: Magnesium hydroxide 724mg

Information already included in arm/group description.

Other Names:

Magnesiumoxide

Outcome Measures

Primary Outcome Measures

The percentage of patients with a score of <30 of the Bowel Function Index [On day 14]
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).

Secondary Outcome Measures

The EQ5D [On day 0 and day 14]
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).
Rome IV criteria for opioid-induced constipation [On day 0 and day 14]
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
Cancer pain score [On day 0 and day 14]
Numeric Rating SDcale, ranging from 0 to 10
Patient satisfaction with laxative [On day 14]
A single four-item question, ranging from unsatisfied to very satisfied.
Side effects of laxatives [On day 14]
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)
Cost-effectiveness of macrogol/electrolytes compared to magnesium hydroxide [On day 14]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

In order to be eligible to participate in this study, a subject must meet all of the following criteria:

Patients with metastatic 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.

Exclusion Criteria:

A potential subject who meets any of the following criteria will be excluded from participation in this study:

Patients with contra-indications for laxatives
Use of laxatives during the last four weeks
Severely impaired renal function (serum creatinine >180 umol/l)
Estimated life expectancy <3 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Flevoziekenhuis	Almere	Flevoland	Netherlands	1315 RA
2	Rijnstate Ziekenhuis	Arnhem	Gelderland	Netherlands	6815 AD
3	Radboud university Medical center Nijmegen	Nijmegen	Gelderland	Netherlands	6525 GA
4	Jeroen Bosch Ziekenhuis	's Hertogenbosch	Noord-Brabant	Netherlands	5223 GZ
5	Amsterdam UMC, location VUmc	Amsterdam	Noord-Holland	Netherlands	1081 HV
6	Spaarne Gasthuis	Hoofddorp	Noord-Holland	Netherlands	2134 TM
7	Leiden University Medical Center	Leiden	Zuid-Holland	Netherlands	2333 ZA
8	Erasmus Medical Center	Rotterdam	Zuid-Holland	Netherlands	3015 GD
9	University Medical Center Groningen	Groningen		Netherlands	9713 GZ
10	University Medical Center Utrecht	Utrecht		Netherlands	3584 CX