Subcutaneous Versus Intravenous Morphine When Switching From Oral to Parenteral Route in Palliative Cancer Patients

NCT ID: NCT05236647

Last Updated: 2025-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-08
• Study Completion Date: 2025-01-31

Brief Summary

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.

Detailed Description

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.

Conditions

Pain Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Intravenous morphine infusion

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.

Group Type: EXPERIMENTAL

Morphine

Intervention Type: DRUG

Intravenous morphine infusion compared to subcutaneous morphine infusion

Subcutaneous morphine infusion

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.

Group Type: ACTIVE_COMPARATOR

Morphine

Intervention Type: DRUG

Intravenous morphine infusion compared to subcutaneous morphine infusion

Interventions

Morphine

Intravenous morphine infusion compared to subcutaneous morphine infusion

Intervention Type: DRUG

Other Intervention Names

Morphine hydrochloride trihydrate

Eligibility Criteria

Inclusion Criteria

• Unsatisfactory pain control despite titration of oral or transdermal opioids
• Planned discharge to home or nursing home

Exclusion Criteria

• Estimated survival time <2 weeks
• A clear indication for either intravenous or subcutaneous administration
• Patient unable to report patient reported outcomes needed in the study due to language barriers or cognitive impairment
• Impossible to establish venous access

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Akershus

OTHER

Sponsor Role: lead

Responsible Party

Olav Fredheim

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Olav Fredheim, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Akershus

Locations

Akershus University Hospital

Lørenskog, , Norway

Countries

Norway

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2021/291056(REK)

Identifier Type: -

Identifier Source: org_study_id