Prevention of Opioid-induced Constipation in Patients With Advanced Cancer

Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorAmsterdam UMC, location VUmc

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 volunteers

Qualifiers

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

Design model

Parallel

Treatments tested in this trial

  • Macrogol Only Product in Oral Dose Form

    Drug

    Information already included in arm/group description.

  • Magnesium hydroxide 724mg

    Drug

    Information already included in arm/group description.

Treatment groups

258 Participants
are divided into 2 treatment groups
Group A: Macrogol/electrolytesActive comparator 1 intervention
Group B: Magnesium hydroxideActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

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).

Time frame
On day 14

Secondary outcomes

1

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).

Time frame
On day 0 and day 14
2

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

Time frame
On day 0 and day 14
3

Cancer pain score

Numeric Rating SDcale, ranging from 0 to 10

Time frame
On day 0 and day 14
4

Patient satisfaction with laxative

A single four-item question, ranging from unsatisfied to very satisfied.

Time frame
On day 14

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

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