ParOP: Paracetamol in Addition to WHO Step III Opioids in Chronic Cancer Pain Control
Study Details
Study Description
Brief Summary
Blinded withdrawal of regular co-medication with paracetamol in chronic pain patients under strong opioids on pain control.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
Chronic pain cancer patients receiving a strong opioid in combination with paracetamol in a minimum dose of 3 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 1-10). In the second study phase (days 11-20) 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.
Between the on-site visits at baseline, day 10 and day 20, patients will be followed up by phone calls every 3 days (±1d) and will have an End of Study visit on day 20. 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
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Paracetamol
|
Drug: Paracetamol
Paracetamol in the dose already used
|
| Placebo Comparator: Placebo
|
Drug: Placebo
Blinded withdrawal of regular co-medication with paracetamol
|
Outcome Measures
Primary Outcome Measures
- VAS score (average pain intensity) [Study day 10]
Secondary Outcome Measures
- Average pain using the Brief Pain Inventory (BPI) [On each study day, up to 20 days]
- Minimum pain using the Brief Pain Inventory (BPI) [On each study day, up to 20 days]
- Worst pain using the Brief Pain Inventory (BPI) [On each study day, up to 20 days]
- Current pain using the Brief Pain Inventory (BPI) [On each study day, up to 20 days]
- Average pain using the Brief Pain Inventory (BPI) [During the last four days of each study phase (days 7-10 und 17-20)]
- Minimum pain using the Brief Pain Inventory (BPI) [During the last four days of each study phase(days 7-10 und 17-20)]
- Worst pain using the Brief Pain Inventory (BPI) [During the last four days of each study phase (days 7-10 und 17-20)]
- Current pain using the Brief Pain Inventory (BPI) [During the last four days of each study phase (days 7-10 und 17-20)]
- Cumulative dose of rescue medication used [On each study day, up to 20 days]
- Cumulative dose of rescue medication used [During the last four days of each study phase (days 7-10 und 17-20)]
- Number of rescue medication used [On each study day, up to 20 days]
- Number of rescue medication used [During the last four days of each study phase (days 7-10 und 17-20)]
- Percentage increase in pain compared to baseline [During each study phase (days 1-10 and days 11-20)]
- Percentage of patients meeting the predefined pain threshold [During each study phase (days 1-10 and days 11-20)]
- Subjective ratings of quality of sleep using the Brief Pain Inventory (BPI) [At baseline and during each study phase (days 1-10 and days 11-20)]
- Subjective ratings of quality of life using the EQ-5D-5L questionnaire [At baseline and during each study phase (days 1-10 and days 11-20)]
- Subjective ratings of functioning using the Brief Pain Inventory (BPI) and the EQ-5D-5L questionnaire [At baseline and during each study phase (days 1-10 and days 11-20)]
- 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 10 and 20]
Study vs. baseline
- Participant's impression of change [At day 10 and 20]
11-point scale tool between -5 ="very much worse" and +5 ="completely recovered"
- Participants' guess regarding their assigned group (verum or placebo) [At day 10 and 20]
- Assessment of serious adverse events [During each study phase (days 1-10 and days 11-20)]
- Assessment of specific adverse events: nausea/vomiting [During each study phase (days 1-10 and days 11-20)]
- Assessment of specific adverse events: drowsiness [During whole study (days 1-20)]
- Assessment of specific adverse events: appetite [During each study phase (days 1-10 and days 11-20)]
- Assessment of specific adverse events: constipation [During each study phase (days 1-10 and days 11-20)]
- Assessment of other adverse events [During each study phase (days 1-10 and days 11-20)]
- Number of withdrawals from study or treatment [During each study phase (days 1-10 and days 11-20)]
- Time (days) of stable pain control [During whole study (days 1-20)]
- Patients' potential to develop hepatotoxicity (investigation of risk factors) [During whole study (days 1-20)]
- % hours with pain/24h [On each study day, up to 20 days]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male and female cancer patients receiving a WHO step III opioid (i.e. morphine, oxycodone, methadone, fentanyl, hydromorphone, or buprenorphine) in combination with paracetamol (minimum dose 3 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Inselspital, Bern University Hospital | Bern | Switzerland |
Sponsors and Collaborators
- University Hospital Inselspital, Berne
- Swiss National Science Foundation
Investigators
- Principal Investigator: Evangelia Liakoni, Inselspital, Bern University Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BASEC-ID: 2021-01518