Clinical trial NCT05088876: Paracetamol in Addition to WHO Step III Opioids in Chronic Cancer Pain Control
Official title: Paracetamol in Addition to WHO Step III Opioids in Chronic Cancer Pain Control - a Randomized, Double-blind, Placebo-controlled, Non-inferiority Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Pain
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
Collaborators: name: Swiss National Science Foundation
First posted: 2021-10-22
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: VAS score (average pain intensity)
timeFrame: Study day 7
Secondary outcomes:
measure: Average pain using the Brief Pain Inventory (BPI)
timeFrame: On each study day, up to 14 days
measure: Minimum pain using the Brief Pain Inventory (BPI)
timeFrame: On each study day, up to 14 days
measure: Worst pain using the Brief Pain Inventory (BPI)
timeFrame: On each study day, up to 14 days
measure: Current pain using the Brief Pain Inventory (BPI)
timeFrame: On each study day, up to 14 days
measure: Average pain using the Brief Pain Inventory (BPI)
timeFrame: During the last four days of each study phase (days 4-7 und 11-14)
measure: Minimum pain using the Brief Pain Inventory (BPI)
timeFrame: During the last four days of each study phase(days 4-7 und 11-14)
measure: Worst pain using the Brief Pain Inventory (BPI)
timeFrame: During the last four days of each study phase (days 4-7 und 11-14)
measure: Current pain using the Brief Pain Inventory (BPI)
timeFrame: During the last four days of each study phase (days 4-7 und 11-14)
measure: Cumulative dose of rescue medication used
timeFrame: On each study day, up to 14 days
measure: Cumulative dose of rescue medication used
timeFrame: During the last four days of each study phase (days 4-7 und 11-14)
measure: Number of rescue medication used
timeFrame: On each study day, up to 14 days
measure: Number of rescue medication used
timeFrame: During the last four days of each study phase (days 4-7 und 11-14)
measure: Percentage increase in pain compared to baseline
timeFrame: During each study phase (days 1-7 and days 8-14)
measure: Percentage of patients meeting the predefined pain threshold
timeFrame: During each study phase (days 1-7 and days 8-14)
measure: Subjective ratings of quality of sleep using the Brief Pain Inventory (BPI)
timeFrame: At baseline and during each study phase (days 1-7 and days 8-14)
measure: Subjective ratings of quality of life using the EQ-5D-5L questionnaire
timeFrame: At baseline and during each study phase (days 1-7 and days 8-14)
measure: Subjective ratings of functioning using the Brief Pain Inventory (BPI) and the EQ-5D-5L questionnaire
timeFrame: At baseline and during each study phase (days 1-7 and days 8-14)
measure: Patients' expectation regarding pain relief from paracetamol prior to study treatment paracetamol using the Expectation for Treatment Scale (ETS)
timeFrame: Prior to study treatment
measure: Question about participant's preference
timeFrame: At day 7 and 14
measure: Participant's impression of change
timeFrame: At day 7 and 14
measure: Participants' guess regarding their assigned group (verum or placebo)
timeFrame: At day 7 and 14
measure: Assessment of serious adverse events
timeFrame: During each study phase (days 1-7 and days 8-14)
measure: Assessment of specific adverse events: nausea/vomiting
timeFrame: During each study phase (days 1-7 and days 8-14)
measure: Assessment of specific adverse events: drowsiness
timeFrame: During whole study (days 1-14)
measure: Assessment of specific adverse events: appetite
timeFrame: During each study phase (days 1-7 and days 8-14)
measure: Assessment of specific adverse events: constipation
timeFrame: During each study phase (days 1-7 and days 8-14)
measure: Assessment of other adverse events
timeFrame: During each study phase (days 1-7 and days 8-14)
measure: Number of withdrawals from study or treatment
timeFrame: During each study phase (days 1-7 and days 8-14)
measure: Time (days) of stable pain control
timeFrame: During whole study (days 1-14)
measure: Patients' potential to develop hepatotoxicity (investigation of risk factors)
timeFrame: During whole study (days 1-14)
measure: % hours with pain/24h
timeFrame: On each study day, up to 14 days
Other outcomes:
Locations:
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Bern
country: Switzerland
facility: Inselspital, Bern University Hospital
Study officials:
affiliation: Inselspital, Bern University Hospital
name: Evangelia Liakoni
role: PRINCIPAL_INVESTIGATOR
References: