Neurotoxic Adverse Effects of Morphine and Oxycodone for Pain in Terminal Patients With Diminished Renal Function

Summary

Significant pain is a common condition in dying patients. Continuous subcutaneous infusion (CSCI) of opioids is the cornerstone in treatment of pain in this last phase of life. Although morphine is the most frequent used opioid in this respect, burdensome adverse effects, like delirium and allodynia/hyperalgesia, can occur in dying patients, due to accumulation of morphine metabolites in decreasing renal function. Oxycodone seems preferable in this situation, as central effects of circulating metabolites of oxycodone are negligible. However, studies of sufficient quality investigating the clinical effect of this hypothesis are lacking at the moment.

This study investigates whether there is a difference in occurrence of delirium and allodynia/hyperalgesia between oxycodone and morphine. Residents of hospices and somatic or psychogeriatric (PG) wards of nursing homes in the Netherlands, who are eligible for start of CSCI of an opioid for the treatment of pain in the terminal phase of life, are randomly assigned to one of two groups. One group receives CSCI of oxycodone and the other group CSCI of morphine. 117 patients per group are needed. Occurrence of delirium and allodynia/hyperalgesia is assessed three times a week until death of the participant. Quality of dying, as perceived by the patient's relatives, is assessed in an interview with a relative after death.

Conditions

• Pain
• Terminal Illness
• Renal Impairment

Interventions

DRUG

Oxycodone

Both continuous administration by a syringe driver as well as bolus administration every 4 hours will be regarded as continuous subcutaneous infusion (CSCI). Dosage and dosage modifications are in accordance with the Dutch national guideline.

DRUG

Morphine

Both continuous administration by a syringe driver as well as bolus administration every 4 hours will be regarded as continuous subcutaneous infusion (CSCI). Dosage and dosage modifications are in accordance with the Dutch national guideline.

Sponsors & Collaborators

• ZonMw: The Netherlands Organisation for Health Research and Development

  collaborator OTHER

• Envida, Maastricht, The Netherlands

  collaborator UNKNOWN

• Maastricht University Medical Center

  lead OTHER

Principal Investigators

• Marieke HJ van den Beuken-van Everdingen, MD PhD · Maastricht University Medical Center, Center of Expertise in Palliative Care

• Mark JM Martens, MD · Maastricht University Medical Center, Center of Expertise in Palliative Care

• Daisy JA Janssen, MD PhD · Maastricht University Medical Center, Center of Expertise in Palliative Care

• Jos MG Schols, MD PhD · Maastricht University Medical Center, Dep. of Health Services and Ageing, Care and Public Health Research Institute (CAPHRI)

• Sander MJ van Kuijk, PhD · Maastricht University Medical Center, Dep. of Clinical Epidemiology and Medical Technology Assessment (KEMTA)

Study Design

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-06-04

Primary Completion

2018-12-19

Completion

2018-12-19

Countries

• Netherlands

Study Locations