Pain CancerPhase 3SIMNCT05236647
Subcutaneous Versus Intravenous Morphine When Switching From Oral to Parenteral Route in Palliative Cancer Patients
A Phase 3 study testing Morphine in people with Pain Cancer, run by University Hospital, Akershus at 1 site in Norway.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pain Cancer
- What is being tested?
- Morphine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteNorway
- Study dates
- 8 Mar 2022to 31 Jan 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Unsatisfactory pain control despite titration of oral or transdermal opioids
- Planned discharge to home or nursing home
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The SIM-study: A Randomized Controlled Trial of Subcutaneous Versus Intravenous Morphine When Switching From Oral to Parenteral Route in 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.
Read the 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
- Being tested
- Morphine
- Medical subject headings
- Cancer Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MorphineDrug
Also called Morphine hydrochloride trihydrate
Intravenous morphine infusion compared to subcutaneous morphine infusion
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Morphine |
| 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. Receives: Drug: Morphine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 48 hours
Secondary outcomes (6)
Number of patients not reaching adequate pain relief.
Number of patients in each arm not reaching adequate pain relief within 48 hours.
Measured: 48 hours
Number of bolus doses first 24 hours and 48 hours
Total number of bolus doses first 24 hours and 48 hours
Measured: 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.
Measured: 60 minutes
Time to maximum plasma concentration (Tmax).
Time to maximum plasma concentration (Tmax) after bolus dose of morphine.
Measured: 120 minutes
Maximum plasma concentration (Cmax).
Maximum plasma concentration (Cmax) after bolus dose of morphine
Measured: 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.
Measured: 120 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2022
- Study start8 Mar 2022
- Primary completion31 Jan 2025
- Study completion31 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pain CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Akershus
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Olav Fredheim, University Hospital, Akershus
- Investigators
- Olav Fredheim, MD PhD, Principal investigator, University Hospital, Akershus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05236647
- Sponsor's protocol ID
- 2021/291056(REK)
- Acronym
- SIM
- Status last verified
- Mar 2025
- First submitted
- 26 Jan 2022
- Last updated
- 6 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The SIM-study: A Randomized Controlled Trial of Subcutaneous Versus Intravenous Morphine When Switching From Oral to Parenteral Route in Palliative Cancer Patients
- ClinicalTrials.gov ID
- NCT05236647
- Acronym / sponsor ID
- SIM / 2021/291056(REK)
- Conditions
- Pain Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- University Hospital, AkershusUniversity, hospital or other
- Study start
- 8 Mar 2022 (actual)
- Primary completion
- 31 Jan 2025 (actual)
- Study completion
- 31 Jan 2025 (actual)
- First posted
- 11 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intravenous morphine infusion | Experimental | Drug: MorphineMorphine 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 | Drug: MorphineMorphine 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Unsatisfactory pain control despite titration of oral or transdermal opioids
- Planned discharge to home or nursing home
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MorphineAlso: Morphine hydrochloride trihydrateIntravenous morphine infusion compared to subcutaneous morphine infusion | Drug | Intravenous morphine infusion, Subcutaneous morphine infusion |
Primary outcome
Time from initiation of i.v./s.c. morphine to stable infusion rate is reached
Time frame: 48 hours
Time from initiation of i.v./s.c. morphine to stable infusion rate is reached
6 secondary outcomes
Number of patients not reaching adequate pain relief.
Time frame: 48 hours
Number of bolus doses first 24 hours and 48 hours
Time frame: 24 and 48 hours
Time from bolus administration to clinically significant pain relief
Time frame: 60 minutes
Time to maximum plasma concentration (Tmax).
Time frame: 120 minutes
Maximum plasma concentration (Cmax).
Time frame: 120 minutes
Area under the plasma concentration versus time curve (AUC).
Time frame: 120 minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Olav Fredheim, MD PhD principal investigator
University Hospital, Akershus
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Morphine in people with Pain Cancer, run by University Hospital, Akershus at 1 site in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time from initiation of i.v./s.c. morphine to stable infusion rate is reached (time frame: 48 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2025.