Cancer pain not responding to oral opioids in palliative cancer patient, where switching to the parenteral route is indicated.
Conditions
Interventions
Trade Name: Morphine Orifarm Healthcare 20 mg/ml inj or 10 mg/ml inj.
Product Name: Morphine
Pharmaceutical Form: Solution for injection/infusion
Pharmaceutical form of the placebo: Solution for injec
Sponsors
Akershus University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All of the following conditions must apply to the prospective patient at screening prior to receiving study agent: • Unsatisfactory pain control despite titration of oral or transdermal opioids • Planned discharge to home or nursing home • The physician considers the appropriate starting dose to be either morphine 5 mg/ml with infusion rate 0.2 to 0.8 ml/h or morphine 10 mg/ml with infusion rate 0.2 to 0.8 ml/h. • Signed informed consent from the patient • Patient available for admission to Department of Palliative Medicine in time to start infusion between 11 am and 3 pm Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: • A clear indication for either intravenous or subcutaneous administration (by consensus of two senior consultants in palliative medicine) • Patient unable to report patient reported outcomes needed in the study due to language barriers, cognitive impairment, or delirium. • Impossible to establish venous access • Allergy or previous serious adverse effects from morphine • Opioid treatments other than oral/parenteral morphine, oral/parenteral oxycodone and transdermal/transmucosal fentanyl. • Contraindications to use of morphine. - Severe renal failure (estimated glomerular filtration rate < 30 based on kreatinin) • Strong indication for start of morphine infusion outside of the time interval of 11 am to 3 pm • Estimated survival time <2 weeks based on clinical judgement (by consensus of two senior consultants in palliative medicine) • Severe cachecia or peripheral edemas which are relative contraindications to the subcutaneous route of administration (clinical judgement by the responsible physician) Patients with Hb <9 g/dL (7.0 – 9.9 g/dL is considered moderate anemia) will not be included in the pharmacokinetic analyses because it can not be ruled out that the loss of 100-150 ml blood might be harmful in some of these patients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The overall objective is to establish whether either the intravenous or subcutaneous route of administration has clinically significant advantages when parenteral administration or morphine is started with a combination of continuous infusion and bolus doses in palliative cancer patients. Primary research question: •Is there a difference between s.c. and i.v. administration of morphine in how quickly pain control is achieved after initiation of a continuous infusion? ;Secondary Objective: Secondary research questions: •Is there a clinically significant difference between s.c. and i.v. administration of morphine in time from administration of bolus dose to clinically significant pain relief? •How large is the difference in the key pharmacokinetic parameters Tmax, Cmax, and AUC0-60 after s.c. and i.v. administration of morphine bolus doses during morphine infusion in palliative cancer patients? ;Primary end point(s): •Time from initiation of infusion until final infusion rate, defined as the time from start of infusion until last change in dosing during double blind double dummy treatment. ;Timepoint(s) of evaluation of this end point: The 48-hours intervention period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Time from bolus administration to clinically significant pain relief (change of 2 on 0-10 NRS) • Comparision of Tmax, Cmax, and size of AUC0-60 after bolus doses during morphine infusion. • Number of bolus doses first 24 and 48 hours. • The share of patients not reaching acceptable pain relief within 48 hours (assessed by whether physician and patient concludes that further adjustments in pain medication is required after 48 hours). ;Timepoint(s) of evaluation of this end point: All secondary endpoints will be evaluated within the 48-hour intervention or at the end of the intervention period. | — |
Countries
Norway
Contacts
Public ContactPrincipal investigator
Akershus University Hospital
Outcome results
None listed