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

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ClinicalTrials.gov Identifier: NCT03616639
Recruitment Status : Terminated (Insufficient inclusion of subjects)
First Posted : August 6, 2018
Last Update Posted : March 18, 2019
Sponsor:
Collaborators:
ZonMw: The Netherlands Organisation for Health Research and Development
Envida, Maastricht, The Netherlands
Information provided by (Responsible Party):
Maastricht University Medical Center

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.


Condition or disease Intervention/treatment Phase
Pain Terminal Illness Renal Impairment Drug: Oxycodone Drug: Morphine Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: Neurotoxic Adverse Effects of Morphine and Oxycodone in Continuous Subcutaneous Infusion for Treatment of Pain in Terminal Patients With Diminished Renal Function: a Randomized Controlled Trial
Actual Study Start Date : June 4, 2018
Actual Primary Completion Date : December 19, 2018
Actual Study Completion Date : December 19, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Oxycodone
Continuous subcutaneous infusion (CSCI) of oxycodone.
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.
Other Name: Oxycodone Hydrochloride

Active Comparator: Morphine
Continuous subcutaneous infusion (CSCI) of morphine.
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.
Other Name: Morphine Hydrochloride




Primary Outcome Measures :
  1. Occurrence of delirium [ Time Frame: Daily, from date of randomization until date of death, with an estimated average of 1 week. ]
    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.


Secondary Outcome Measures :
  1. Occurrence of allodynia/hyperalgesia [ Time Frame: Three times a week, from date of randomization until date of death, with an estimated average of 1 week. ]
    Presence of allodynia or hyperalgesia is assessed by asking the subject whether respectively lightly brushing with a piece of cotton wool on the skin or performing pin-prick testing provokes pain or aggravates already existing pain. In case the subject is not able to adequately respond verbally the items of the Rotterdam Elderly Pain Observation Scale (REPOS) are used to determine presence of a painful response


Other Outcome Measures:
  1. Time between start of CSCI and death [ Time Frame: From date of randomization until date of death, with an estimated average of 1 week. ]
    Time between the start of CSCI with the assigned opioid and death

  2. Pain scores [ Time Frame: Three times a week, from date of randomization until date of death, with an estimated average of 1 week. ]
    Pain scores (NRS or REPOS) at rest prior to testing for allodynia/hyperalgia

  3. Quality of Dying and Death [ Time Frame: Two weeks after death ]
    Structured interview with a relative to assess the perceived quality of dying.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03616639


Locations
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Netherlands
Envida - De Wilgenhof
Bunde, Limburg, Netherlands, 6241 BH
Envida - De Bron
Eijsden, Limburg, Netherlands, 6245 EL
Envida - Klein Gulpen
Gulpen, Limburg, Netherlands, 6271 AA
Envida - Hospice Trajectum
Maastricht, Limburg, Netherlands, 6211 LS
Envida - Larisa
Maastricht, Limburg, Netherlands, 6211 LX
Envida - De Mins
Maastricht, Limburg, Netherlands, 6218 SM
Envida - Koepelhof
Maastricht, Limburg, Netherlands, 6224 LW
Envida - De Zeven Bronnen
Maastricht, Limburg, Netherlands, 6225 AG
Envida - Hagerpoort
Maastricht, Limburg, Netherlands, 6225 GA
Envida - Grubbeveld
Maastricht, Limburg, Netherlands, 6226 NB
Envida - Croonenhoff
Maastricht, Limburg, Netherlands, 6227 SZ
Envida - La Valence
Maastricht, Limburg, Netherlands, 6229 VN
Envida - De Lommer
Margraten, Limburg, Netherlands, 6269 AM
Envida - Appelgaard
Margraten, Limburg, Netherlands, 6269 DD
Envida - Beukeloord
Meerssen, Limburg, Netherlands, 6231 JZ
Sponsors and Collaborators
Maastricht University Medical Center
ZonMw: The Netherlands Organisation for Health Research and Development
Envida, Maastricht, The Netherlands
Investigators
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Principal Investigator: Marieke HJ van den Beuken-van Everdingen, MD PhD Maastricht University Medical Center, Center of Expertise in Palliative Care
Study Chair: 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 Documents (Full-Text)

Documents provided by Maastricht University Medical Center:
Informed Consent Form: Normal subjects  [PDF] August 18, 2017


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Responsible Party: Maastricht University Medical Center
ClinicalTrials.gov Identifier: NCT03616639     History of Changes
Other Study ID Numbers: NL62110.068.17
First Posted: August 6, 2018    Key Record Dates
Last Update Posted: March 18, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Oxycodone
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Morphine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents