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

NCT03616639 | Terminated Phase 4 DMC

• 1 other identifier: NL62110.068.17
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 15

Brief 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

Outcome Measures

Primary Outcomes (1)

• Occurrence of delirium

  The Delirium Observation Screening (DOS)-scale is scored by the nursing staff on a daily basis to screen for presence of delirium. In case this screening instrument indicates a possible presence of delirium, the clinical diagnosis of delirium will be confirmed or reject by a psychologist in accordance with the DSM-IV-TR criteria.

  Daily, from date of randomization until date of death, with an estimated average of 1 week.

Secondary Outcomes (1)

• Occurrence of allodynia/hyperalgesia

  Three times a week, from date of randomization until date of death, with an estimated average of 1 week.

Other Outcomes (3)

• Time between start of CSCI and death

  From date of randomization until date of death, with an estimated average of 1 week.

• Pain scores

  Three times a week, from date of randomization until date of death, with an estimated average of 1 week.

• Quality of Dying and Death

  Two weeks after death

Study Arms (2)

Oxycodone

EXPERIMENTAL

Continuous subcutaneous infusion (CSCI) of oxycodone.

Drug: Oxycodone

Morphine

ACTIVE COMPARATOR

Continuous subcutaneous infusion (CSCI) of morphine.

Drug: Morphine

Interventions

Oxycodone DRUG

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.

Also known as: Oxycodone Hydrochloride

Oxycodone

Morphine DRUG

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.

Also known as: Morphine Hydrochloride

Morphine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator
• Envida, Maastricht, The Netherlands: collaborator

Study Sites (15)

Envida - De Wilgenhof

Bunde, Limburg, 6241 BH, Netherlands

Location

Envida - De Bron

Eijsden, Limburg, 6245 EL, Netherlands

Location

Envida - Klein Gulpen

Gulpen, Limburg, 6271 AA, Netherlands

Location

Envida - Hospice Trajectum

Maastricht, Limburg, 6211 LS, Netherlands

Location

Envida - Larisa

Maastricht, Limburg, 6211 LX, Netherlands

Location

Envida - De Mins

Maastricht, Limburg, 6218 SM, Netherlands

Location

Envida - Koepelhof

Maastricht, Limburg, 6224 LW, Netherlands

Location

Envida - De Zeven Bronnen

Maastricht, Limburg, 6225 AG, Netherlands

Location

Envida - Hagerpoort

Maastricht, Limburg, 6225 GA, Netherlands

Location

Envida - Grubbeveld

Maastricht, Limburg, 6226 NB, Netherlands

Location

Envida - Croonenhoff

Maastricht, Limburg, 6227 SZ, Netherlands

Location

Envida - La Valence

Maastricht, Limburg, 6229 VN, Netherlands

Location

Envida - De Lommer

Margraten, Limburg, 6269 AM, Netherlands

Location

Envida - Appelgaard

Margraten, Limburg, 6269 DD, Netherlands

Location

Envida - Beukeloord

Meerssen, Limburg, 6231 JZ, Netherlands

Location

MeSH Terms

Conditions

Pain; Renal Insufficiency

Interventions

Oxycodone; Morphine

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Codeine; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Marieke HJ van den Beuken-van Everdingen, MD PhD

  Maastricht University Medical Center, Center of Expertise in Palliative Care

  PRINCIPAL INVESTIGATOR

• Mark JM Martens, MD

  Maastricht University Medical Center, Center of Expertise in Palliative Care

  STUDY CHAIR

• Daisy JA Janssen, MD PhD

  Maastricht University Medical Center, Center of Expertise in Palliative Care

  STUDY CHAIR

• Jos MG Schols, MD PhD

  Maastricht University Medical Center, Dep. of Health Services and Ageing, Care and Public Health Research Institute (CAPHRI)

  STUDY CHAIR

• Sander MJ van Kuijk, PhD

  Maastricht University Medical Center, Dep. of Clinical Epidemiology and Medical Technology Assessment (KEMTA)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2018
• First Posted: August 6, 2018
• Study Start: June 4, 2018
• Primary Completion: December 19, 2018
• Study Completion: December 19, 2018
• Last Updated: March 18, 2019

Record last verified: 2019-03

Locations

NL (15)