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The investigators aim to establish whether the intravenous or the subcutaneous route of administration has clinically significant advantages when parenteral administration of morphine is started with a combination of continuous infusion and bolus doses in palliative cancer patients.
Patients admitted to a Hospital palliative medicine unit with an indication for parenteral administration of morphine will be recruited.
The patients will have two similar infusion pumps with continuous infusion and bolus function. One infusion pump will be connected to an intravenous line, the other to a subcutaneous line. One pump contains morphine, one placebo. The primary endpoint is the time from initiation of infusion with titration to the final infusion rate that provides pain control is reached.
Intravenous administration has theoretical advantages in more predictable pharmacokinetics and shorter time to maximum effect. Subcutaneous administration is less invasive, requires less specialized personnel and equipment, and probably poses a lower risk of complications than an intravenous line. Traditionally the subcutaneous route has been the recommended first choice for parenteral administration of opioids for palliative cancer patients.
The investigators aim to establish whether the intravenous or the subcutaneous route of administration has clinically significant advantages when parenteral administration of morphine is started with a combination of continuous infusion and bolus doses in palliative cancer patients.
Patients admitted to a Hospital palliative medicine unit with an indication for parenteral administration of morphine will be recruited.
The patients will have two similar infusion pumps with continuous infusion and bolus function. One infusion pump will be connected to an intravenous line, the other to a subcutaneous line. One pump contains morphine, one placebo. The primary endpoint is the time from initiation of infusion with titration to the final infusion rate that provides pain control is reached. Secondary endpoints are time from bolus administration to pain relief, comparison of Tmax, Cmax, and size of AUC0-60 after bolus doses, the number of bolus doses first 24 and 48 hours, and the number of patients reaching acceptable pain relief within 48 hours.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intravenous morphine infusion | Experimental | Morphine 10 mg/ml or morphine 20 mg/ml will be diluted with normal saline to 5 mg/ml or 10 mg/ml. Both active study medication and placebo will be prepared in 100 ml drug containers suitable for the infusion pump. The patient will have two similar infusion pumps. Morphine infusion connected to an i.v. line, placebo (normal saline) connected to a s.c line. Bolus dose will initially be equal to dose/hour. The nurse will administer bolus doses on both pumps (placebo and morphine pump) simultaneously. Patient reported pain intensity (NRS 0-10) and whether the bolus dose was initiated by the patient or the nurse will be recorded before each bolus dose. Bolus dose will be equally increased if/when the infusion rate is increased. If the bolus dose is ineffective, the bolus dose can be increased in steps of 0.1 ml until an effective dose is reached. |
|
| Subcutaneous morphine infusion | Active Comparator | Morphine 10mg/ml or morphine 20 mg/ml will be diluted with normal saline to 5 mg/ml or 10 mg/ml. Both active study medication and placebo will be prepared in 100 ml drug containers suitable for the infusion pump. The patient will have two similar infusion pumps. Morphine infusion connected to a s.c. line, placebo (normal saline) connected to a i.v. line. Bolus dose will initially be equal to dose/hour. The nurse will administer bolus doses on both pumps (placebo and morphine pump) simultaneously. Patient reported pain intensity (NRS 0-10) and whether the bolus dose was initiated by the patient or the nurse will be recorded before each bolus dose. Bolus dose will be equally increased if/when the infusion rate is increased. If the bolus dose is ineffective, the bolus dose can be increased in steps of 0.1 ml until an effective dose is reached. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Morphine | Drug | Intravenous morphine infusion compared to subcutaneous morphine infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Time from initiation of i.v./s.c. morphine to stable infusion rate is reached | Time from initiation of i.v./s.c. morphine to stable infusion rate is reached | 48 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Number of patients not reaching adequate pain relief. | Number of patients in each arm not reaching adequate pain relief within 48 hours. | 48 hours |
| Number of bolus doses first 24 hours and 48 hours |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Olav Fredheim, MD PhD | University Hospital, Akershus | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Akershus University Hospital | Lørenskog | 1478 | Norway |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 23, 2023 | Dec 19, 2023 | SAP_000.pdf |
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| ID | Term |
|---|---|
| D000072716 | Cancer Pain |
| ID | Term |
|---|---|
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D009020 | Morphine |
| ID | Term |
|---|---|
| D009022 | Morphine Derivatives |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
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|
Total number of bolus doses first 24 hours and 48 hours
| 24 and 48 hours |
| Time from bolus administration to clinically significant pain relief | Time from bolus administration to a reduction of minimum 2 on a 0-10 numeric rating scale. | 60 minutes |
| Time to maximum plasma concentration (Tmax). | Time to maximum plasma concentration (Tmax) after bolus dose of morphine. | 120 minutes |
| Maximum plasma concentration (Cmax). | Maximum plasma concentration (Cmax) after bolus dose of morphine | 120 minutes |
| Area under the plasma concentration versus time curve (AUC). | Area under the plasma concentration versus time curve (AUC) after bolus administration of morphine. | 120 minutes |
| D006571 |
| Heterocyclic Compounds |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |