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

• Status: Terminated
• Trial end date: 2018-12-19
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Maastricht University Medical Center
• Collaborators: Envida, Maastricht, The Netherlands; ZonMw: The Netherlands Organisation for Health Research and Development
• Treatments: Morphine; Oxycodone

Criteria

Inclusion Criteria:

• minimal age of 18 years at the time of inclusion;

• the subject is in the terminal phase, i.e. death in the near future is expected by the treating physician;

• start of CSCI with an opioid for treatment of pain is indicated by the treating physician;

• willingness to allow one-time blood collection for assessment of renal function (eGFR);

• a signed informed consent is given by the participant or his/her legal representative.

Exclusion Criteria:

• delirium at the time of inclusion;

• opioid induced hyperalgesia (OIH) at the time of inclusion;

• a medical necessity to apply a different opioid than morphine or oxycodone, such as previously demonstrated non-response to morphine or oxycodone (defined as a complete absence of any pain reduction after appropriate dosage), previously demonstrated unacceptable side effects of morphine or oxycodone, or a medical indication for an opioid with NMDA-receptor-antagonistic properties (currently only known for methadone);

• a documented allergy for morphine or oxycodone.

Subjects with an eGFR >50 ml/min/1.73m2 should not be included in the study, because accumulation of metabolites is considered to be irrelevant in this range of renal functions. Despite this fact, we cannot formulate an unaffected renal function as an exclusion criterion prior to allocation, because the time needed for assessment of the renal function could lead to either an unethical delay in treatment of pain or occurrence of death even before the lab results are known. Therefore renal function is assessed after inclusion. In case a subject turns out to exceed the threshold of 50 ml/min/1.73m2, this will be considered as meeting an extended exclusion criterion and the subject concerned will be replaced by a new subject.