Pain
Conditions
Brief summary
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.
Interventions
DRUGPlacebo
Blinded withdrawal of regular co-medication with paracetamol
DRUGParacetamol
Paracetamol in the dose already used
Sponsors
Insel Gruppe AG, University Hospital Bern
Swiss National Science Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| VAS score (average pain intensity) | Study day 7 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average pain using the Brief Pain Inventory (BPI) | On each study day, up to 14 days | — |
| Minimum pain using the Brief Pain Inventory (BPI) | On each study day, up to 14 days | — |
| Worst pain using the Brief Pain Inventory (BPI) | On each study day, up to 14 days | — |
| Current pain using the Brief Pain Inventory (BPI) | On each study day, up to 14 days | — |
| Cumulative dose of rescue medication used | On each study day, up to 14 days | — |
| Number of rescue medication used | On each study day, up to 14 days | — |
| Percentage increase in pain compared to baseline | During each study phase (days 1-7 and days 8-14) | — |
| Percentage of patients meeting the predefined pain threshold | During each study phase (days 1-7 and days 8-14) | — |
| Subjective ratings of quality of sleep using the Brief Pain Inventory (BPI) | 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 | 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 | 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) | Prior to study treatment | 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) |
| Question about participant's preference | At day 7 and 14 | Study vs. baseline |
| Participant's impression of change | At day 7 and 14 | 11-point scale tool between -5 ="very much worse" and +5 ="completely recovered" |
| Participants' guess regarding their assigned group (verum or placebo) | At day 7 and 14 | — |
| Assessment of serious adverse events | During each study phase (days 1-7 and days 8-14) | — |
| Assessment of specific adverse events: nausea/vomiting | During each study phase (days 1-7 and days 8-14) | — |
| Assessment of specific adverse events: drowsiness | During each study phase (days 1-7 and days 8-14) | — |
| Assessment of specific adverse events: appetite | During each study phase (days 1-7 and days 8-14) | — |
| Assessment of specific adverse events: constipation | During each study phase (days 1-7 and days 8-14) | — |
| Assessment of other adverse events | During each study phase (days 1-7 and days 8-14) | — |
| Number of withdrawals from study or treatment | During each study phase (days 1-7 and days 8-14) | — |
| Time (days) of stable pain control | During whole study (days 1-14) | — |
| Patients' potential to develop hepatotoxicity (investigation of risk factors) | During whole study (days 1-14) | — |
| % hours with pain/24h | On each study day, up to 14 days | — |
Countries
Switzerland
Contacts
PRINCIPAL_INVESTIGATOREvangelia Liakoni
Inselspital, Bern University Hospital
Outcome results
None listed