PainPhase 4ParOPNCT05088876
Paracetamol in Addition to WHO Step III Opioids in Chronic Cancer Pain Control
A Phase 4 study testing Paracetamol in people with Pain, run by Insel Gruppe AG, University Hospital Bern at 2 sites in Switzerland.
Trial summary
Blinded withdrawal of regular co-medication with paracetamol in chronic pain patients under strong opioids on pain control. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pain
- What is being tested?
- Paracetamol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 7 participants
- Where
- 2 sitesSwitzerland
- Study dates
- 28 Aug 2024to 5 Mar 2026
- Phase
- Phase 4
- 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
- Male and female patients receiving a WHO step III opioid (i.e. morphine, oxycodone, methadone, fentanyl, hydromorphone, or buprenorphine) in combination with paracetamol (minimum dose 1.5 g/day)
- Age ≥ 18 at screening
- Ability to understand the study procedures and to provide written informed consent
- Stable analgesia before randomisation, defined as no required changes in the analgesic treatment during the previous 7 days
Who cannot join
- Participation in another interventional trial within 30 days prior to randomisation, with the exception of cancer treatment trials
- Changes of the dosage or start of other (co-)analgesics (e.g. tricyclic antidepressants, neuroleptics, nonsteroidal anti-inflammatory drugs (NSAIDs), dipyrone), within the last 7 days preceding randomisation
- Surgery within the 14 days preceding randomisation or surgery planned within the duration of the study
- Any circumstances, comorbidities or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the study protocol
Trial locations and contacts
2 sites in 1 country.
Switzerland2 sites
Kantonsspital Baden
Baden
Inselspital, Bern University Hospital
Bern
About this study
Official title: Paracetamol in Addition to WHO Step III Opioids in Chronic Cancer Pain Control - a Randomized, Double-blind, Placebo-controlled, Non-inferiority Study
Blinded withdrawal of regular co-medication with paracetamol in chronic pain patients under strong opioids on pain control.
Read the detailed description
Chronic pain patients receiving a strong opioid in combination with paracetamol in a minimum dose of 1.5 g/day will be randomized to receive either paracetamol in the dose already prescribed (group "paracetamol") or an identically looking placebo (group "placebo") using the same schedule during the first study phase (days 1-7). In the second study phase (days 8-14) paracetamol or placebo will be stopped in both arms to assess the effect of pill withdrawal on pain control.
Next to baseline the patients will be instructed to use a pain diary to rate their pain during the study and also document the required opioid rescue doses. Further assessments will include adverse events, subjective ratings of quality of sleep, overall feeling of functioning and quality of life. At the screening visit, patients will also be asked to rate their expected changes in pain relief as a result of co-treatment with paracetamol. At the completion of the study, patients will be asked about their preference and whether, overall, they felt their pain was more poorly controlled during the study.
Adherence will be checked by pill count and measurement of paracetamol blood concentrations. Genotyping of OPRM1, COMT and relevant CYP enzymes and opioid blood concentrations will be assessed as co-variates for pain control.
- Conditions
- Pain
- Being tested
- Placebo, Paracetamol
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Blinded withdrawal of regular co-medication with paracetamol
ParacetamolDrug
Paracetamol in the dose already used
| Study group | Role | What they receive |
|---|---|---|
| Paracetamol | Active comparator | Not described Receives: Drug: Paracetamol |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
VAS score (average pain intensity)
Measured: Study day 7
Secondary outcomes (31)
Average pain using the Brief Pain Inventory (BPI)
Measured: On each study day, up to 14 days
Minimum pain using the Brief Pain Inventory (BPI)
Measured: On each study day, up to 14 days
Worst pain using the Brief Pain Inventory (BPI)
Measured: On each study day, up to 14 days
Current pain using the Brief Pain Inventory (BPI)
Measured: On each study day, up to 14 days
Average pain using the Brief Pain Inventory (BPI)
Measured: During the last four days of each study phase (days 4-7 und 11-14)
Minimum pain using the Brief Pain Inventory (BPI)
Measured: During the last four days of each study phase(days 4-7 und 11-14)
Worst pain using the Brief Pain Inventory (BPI)
Measured: During the last four days of each study phase (days 4-7 und 11-14)
Current pain using the Brief Pain Inventory (BPI)
Measured: During the last four days of each study phase (days 4-7 und 11-14)
Cumulative dose of rescue medication used
Measured: On each study day, up to 14 days
Cumulative dose of rescue medication used
Measured: During the last four days of each study phase (days 4-7 und 11-14)
Number of rescue medication used
Measured: On each study day, up to 14 days
Number of rescue medication used
Measured: During the last four days of each study phase (days 4-7 und 11-14)
Percentage increase in pain compared to baseline
Measured: During each study phase (days 1-7 and days 8-14)
Percentage of patients meeting the predefined pain threshold
Measured: During each study phase (days 1-7 and days 8-14)
Subjective ratings of quality of sleep using the Brief Pain Inventory (BPI)
Measured: At baseline and during each study phase (days 1-7 and days 8-14)
Subjective ratings of quality of life using the EQ-5D-5L questionnaire
Measured: At baseline and during each study phase (days 1-7 and days 8-14)
Subjective ratings of functioning using the Brief Pain Inventory (BPI) and the EQ-5D-5L questionnaire
Measured: At baseline and during each study phase (days 1-7 and days 8-14)
Patients' expectation regarding pain relief from paracetamol prior to study treatment paracetamol using the Expectation for Treatment Scale (ETS)
Five-item ETS with each item rated on a 4-point scale ranging from 1 to 4 (partially disagree, partially agree, agree and definitely agree)
Measured: Prior to study treatment
Question about participant's preference
Study vs. baseline
Measured: At day 7 and 14
Participant's impression of change
11-point scale tool between -5 ="very much worse" and +5 ="completely recovered"
Measured: At day 7 and 14
Participants' guess regarding their assigned group (verum or placebo)
Measured: At day 7 and 14
Assessment of serious adverse events
Measured: During each study phase (days 1-7 and days 8-14)
Assessment of specific adverse events: nausea/vomiting
Measured: During each study phase (days 1-7 and days 8-14)
Assessment of specific adverse events: drowsiness
Measured: During each study phase (days 1-7 and days 8-14)
Assessment of specific adverse events: appetite
Measured: During each study phase (days 1-7 and days 8-14)
Assessment of specific adverse events: constipation
Measured: During each study phase (days 1-7 and days 8-14)
Assessment of other adverse events
Measured: During each study phase (days 1-7 and days 8-14)
Number of withdrawals from study or treatment
Measured: During each study phase (days 1-7 and days 8-14)
Time (days) of stable pain control
Measured: During whole study (days 1-14)
Patients' potential to develop hepatotoxicity (investigation of risk factors)
Measured: During whole study (days 1-14)
% hours with pain/24h
Measured: On each study day, up to 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2021
- Study start28 Aug 2024
- Primary completion5 Mar 2026
- Study completion5 Mar 2026
Why it stopped: Recruitment difficulties
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PainStudies of the same condition, open and under way.
- More trials run by Insel Gruppe AG, University Hospital BernThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Collaborators
- Swiss National Science Foundation
- Responsible party
- Sponsor
- Investigators
- Evangelia Liakoni, Principal investigator, Inselspital, Bern University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05088876
- Sponsor's protocol ID
- BASEC-ID: 2021-01518
- Acronym
- ParOP
- Status last verified
- Apr 2026
- First submitted
- 5 Oct 2021
- Last updated
- 13 Apr 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data that relates to individual, primary publications (and not the whole study database as such) will be deposited in the Bern Open Repository and Information System (BORIS). All efforts will be made to protect privacy and to de-identify the data. Data will be shared on request under the following conditions: A meaningful study question by the requester, outline of the planned analyses, valid methodology, signed data sharing agreement that contains a confidentiality agreement in case of sensitive data.
Publications
Kotoula C, Wertli MM, Streitberger K, Rothschild SI, Limacher A, Hammann F, Krahenbuhl S, Haschke M, Liakoni E. Efficacy of paracetamol added to WHO step III opioids in chronic pain control: study protocol for a randomised, double-blind, placebo-controlled, non-inferiority, multicentre study in Switzerland. BMJ Open. 2025 Dec 31;15(12):e107360. doi: 10.1136/bmjopen-2025-107360.
PubMed 41475826
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Paracetamol in Addition to WHO Step III Opioids in Chronic Cancer Pain Control - a Randomized, Double-blind, Placebo-controlled, Non-inferiority Study
- ClinicalTrials.gov ID
- NCT05088876
- Acronym / sponsor ID
- ParOP / BASEC-ID: 2021-01518
- Conditions
- Pain
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment difficulties
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Collaborators
- Swiss National Science Foundation
- Study start
- 28 Aug 2024 (actual)
- Primary completion
- 5 Mar 2026 (actual)
- Study completion
- 5 Mar 2026 (actual)
- First posted
- 22 Oct 2021 (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.
Blinded withdrawal of regular co-medication with paracetamol in chronic pain patients under strong opioids on pain control.
Detailed description
Chronic pain patients receiving a strong opioid in combination with paracetamol in a minimum dose of 1.5 g/day will be randomized to receive either paracetamol in the dose already prescribed (group "paracetamol") or an identically looking placebo (group "placebo") using the same schedule during the first study phase (days 1-7). In the second study phase (days 8-14) paracetamol or placebo will be stopped in both arms to assess the effect of pill withdrawal on pain control.
Next to baseline the patients will be instructed to use a pain diary to rate their pain during the study and also document the required opioid rescue doses. Further assessments will include adverse events, subjective ratings of quality of sleep, overall feeling of functioning and quality of life. At the screening visit, patients will also be asked to rate their expected changes in pain relief as a result of co-treatment with paracetamol. At the completion of the study, patients will be asked about their preference and whether, overall, they felt their pain was more poorly controlled during the study.
Adherence will be checked by pill count and measurement of paracetamol blood concentrations. Genotyping of OPRM1, COMT and relevant CYP enzymes and opioid blood concentrations will be assessed as co-variates for pain control.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Paracetamol | Active comparator | Drug: Paracetamol |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male and female patients receiving a WHO step III opioid (i.e. morphine, oxycodone, methadone, fentanyl, hydromorphone, or buprenorphine) in combination with paracetamol (minimum dose 1.5 g/day)
- Age ≥ 18 at screening
- Ability to understand the study procedures and to provide written informed consent
- Stable analgesia before randomisation, defined as no required changes in the analgesic treatment during the previous 7 days
Key exclusion criteria (4 listed)
- Participation in another interventional trial within 30 days prior to randomisation, with the exception of cancer treatment trials
- Changes of the dosage or start of other (co-)analgesics (e.g. tricyclic antidepressants, neuroleptics, nonsteroidal anti-inflammatory drugs (NSAIDs), dipyrone), within the last 7 days preceding randomisation
- Surgery within the 14 days preceding randomisation or surgery planned within the duration of the study
- Any circumstances, comorbidities or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the study protocol
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 |
|---|---|---|
| PlaceboBlinded withdrawal of regular co-medication with paracetamol | Drug | Placebo |
| ParacetamolParacetamol in the dose already used | Drug | Paracetamol |
Primary outcome
VAS score (average pain intensity)
Time frame: Study day 7
31 secondary outcomes
Average pain using the Brief Pain Inventory (BPI)
Time frame: On each study day, up to 14 days
Minimum pain using the Brief Pain Inventory (BPI)
Time frame: On each study day, up to 14 days
Worst pain using the Brief Pain Inventory (BPI)
Time frame: On each study day, up to 14 days
Current pain using the Brief Pain Inventory (BPI)
Time frame: On each study day, up to 14 days
Average pain using the Brief Pain Inventory (BPI)
Time frame: During the last four days of each study phase (days 4-7 und 11-14)
Minimum pain using the Brief Pain Inventory (BPI)
Time frame: During the last four days of each study phase(days 4-7 und 11-14)
Worst pain using the Brief Pain Inventory (BPI)
Time frame: During the last four days of each study phase (days 4-7 und 11-14)
Current pain using the Brief Pain Inventory (BPI)
Time frame: During the last four days of each study phase (days 4-7 und 11-14)
Cumulative dose of rescue medication used
Time frame: On each study day, up to 14 days
Cumulative dose of rescue medication used
Time frame: During the last four days of each study phase (days 4-7 und 11-14)
Number of rescue medication used
Time frame: On each study day, up to 14 days
Number of rescue medication used
Time frame: During the last four days of each study phase (days 4-7 und 11-14)
Percentage increase in pain compared to baseline
Time frame: During each study phase (days 1-7 and days 8-14)
Percentage of patients meeting the predefined pain threshold
Time frame: During each study phase (days 1-7 and days 8-14)
Subjective ratings of quality of sleep using the Brief Pain Inventory (BPI)
Time frame: At baseline and during each study phase (days 1-7 and days 8-14)
Subjective ratings of quality of life using the EQ-5D-5L questionnaire
Time frame: At baseline and during each study phase (days 1-7 and days 8-14)
Subjective ratings of functioning using the Brief Pain Inventory (BPI) and the EQ-5D-5L questionnaire
Time frame: At baseline and during each study phase (days 1-7 and days 8-14)
Patients' expectation regarding pain relief from paracetamol prior to study treatment paracetamol using the Expectation for Treatment Scale (ETS)
Time frame: Prior to study treatment
Question about participant's preference
Time frame: At day 7 and 14
Participant's impression of change
Time frame: At day 7 and 14
Participants' guess regarding their assigned group (verum or placebo)
Time frame: At day 7 and 14
Assessment of serious adverse events
Time frame: During each study phase (days 1-7 and days 8-14)
Assessment of specific adverse events: nausea/vomiting
Time frame: During each study phase (days 1-7 and days 8-14)
Assessment of specific adverse events: drowsiness
Time frame: During each study phase (days 1-7 and days 8-14)
Assessment of specific adverse events: appetite
Time frame: During each study phase (days 1-7 and days 8-14)
Assessment of specific adverse events: constipation
Time frame: During each study phase (days 1-7 and days 8-14)
Assessment of other adverse events
Time frame: During each study phase (days 1-7 and days 8-14)
Number of withdrawals from study or treatment
Time frame: During each study phase (days 1-7 and days 8-14)
Time (days) of stable pain control
Time frame: During whole study (days 1-14)
Patients' potential to develop hepatotoxicity (investigation of risk factors)
Time frame: During whole study (days 1-14)
% hours with pain/24h
Time frame: On each study day, up to 14 days
Results and safety
The study was stopped early (reason given: Recruitment difficulties). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2026.
- Derived from this study: PubMed 41475826Kotoula C, Wertli MM, Streitberger K, Rothschild SI, Limacher A, Hammann F, Krahenbuhl S, Haschke M, Liakoni E. Efficacy of paracetamol added to WHO step III opioids in chronic pain control: study protocol for a randomised, double-blind, placebo-controlled, non-inferiority, multicentre study in Switzerland. BMJ Open. 2025 Dec 31;15(12):e107360. doi: 10.1136/bmjopen-2025-107360.
- Individual participant dataSharing planned: Yes. Data that relates to individual, primary publications (and not the whole study database as such) will be deposited in the Bern Open Repository and Information System (BORIS). All efforts will be made to protect privacy and to de-identify the data. Data will be shared on request under the following conditions: A meaningful study question by the requester, outline of the planned analyses, valid methodology, signed data sharing agreement that contains a confidentiality agreement in case of sensitive data.
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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.
Evangelia Liakoni principal investigator
Inselspital, Bern University Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Paracetamol in people with Pain, run by Insel Gruppe AG, University Hospital Bern at 2 sites in Switzerland.
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 4 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: stopped early, as of the sponsor's last update on 13 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Switzerland. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 was stopped early (reason given: Recruitment difficulties). Results are not available in the source record.
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?
VAS score (average pain intensity) (time frame: Study day 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05088876, which also lists 1 linked publication.
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 13 Apr 2026.