Prevention of Opioid-induced Constipation in Patients With Advanced Cancer

Официальное название

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

Обзор

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.

Вмешательства

• Препарат Macrogol Only Product in Oral Dose Form
  Information already included in arm/group description.
• Препарат Magnesium hydroxide 724mg
  Information already included in arm/group description.

Первичные конечные точки

• The percentage of patients with a score of <30 of the Bowel Function Index [Срок оценки: On day 14]

Вторичные конечные точки (6)

• The EQ5D [Срок оценки: On day 0 and day 14]
• Rome IV criteria for opioid-induced constipation [Срок оценки: On day 0 and day 14]
• Cancer pain score [Срок оценки: On day 0 and day 14]
• Patient satisfaction with laxative [Срок оценки: On day 14]
• Side effects of laxatives [Срок оценки: On day 14]
• Cost-effectiveness of macrogol/electrolytes compared to magnesium hydroxide [Срок оценки: On day 14]

Критерии участия

Критерии включения

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.

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

Нидерланды · 13 центров

• Flevoziekenhuis — Almere Stad
• Rijnstate Ziekenhuis — Arnhem
• Radboud university Medical center Nijmegen — Nijmegen
• Jeroen Bosch Ziekenhuis — 's-Hertogenbosch
• Amsterdam UMC, location VUmc — Amsterdam
• Spaarne Gasthuis — Hoofddorp
• Groene Hart Hospital — Gouda
• Leiden University Medical Center — Leiden
• … и ещё 5 центров

Публикации

• 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. PMID 24102611
• Ahmedzai 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. PMID 21937568
• Argoff 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. PMID 26582720
• Bell 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. PMID 19662923
• Christensen 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. PMID 28850447
• Davies 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. PMID 32701649
• Dhingra 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. PMID 22707180
• Drossman 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. PMID 27144617

Идентификаторы

NCT: NCT05216328 · 08440012010002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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