About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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 design
Parallel
Treatments tested in this trial
Macrogol Only Product in Oral Dose Form
DrugInformation already included in arm/group description.
Magnesium hydroxide 724mg
DrugInformation already included in arm/group description.
Treatment groups
Trial outcomes
Primary outcomes
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).
Secondary outcomes
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).
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
Cancer pain score
Numeric Rating SDcale, ranging from 0 to 10
Patient satisfaction with laxative
A single four-item question, ranging from unsatisfied to very satisfied.
Sponsors and contacts
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Amsterdam UMC, location VUmc
Lead sponsor
Leiden University Medical Center
Collaborator
University Medical Center Groningen
Collaborator
Radboud University Medical Center
Collaborator
Erasmus Medical Center
Collaborator
Spaarne Gasthuis
Collaborator
Rijnstate Hospital
Collaborator
Jeroen Bosch Ziekenhuis
Collaborator
Flevoziekenhuis
Collaborator
Martini Hospital Groningen
Collaborator
Haaglanden Medical Centre
Collaborator
UMC Utrecht
Collaborator
Groene Hart Ziekenhuis
Collaborator
Bernhoven Hospital
Collaborator
Isala
Collaborator
Antoni van Leeuwenhoek Hospital
Collaborator