MedPath

Paracetamol in Addition to WHO Step III Opioids in Chronic Cancer Pain Control

Phase 4
Recruiting
Conditions
Pain
Interventions
Drug: Placebo
Registration Number
NCT05088876
Lead Sponsor
Insel Gruppe AG, University Hospital Bern
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
140
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo-
ParacetamolParacetamol-
Primary Outcome Measures
NameTimeMethod
VAS score (average pain intensity)Study day 7
Secondary Outcome Measures
NameTimeMethod
Worst pain using the Brief Pain Inventory (BPI)During the last four days of each study phase (days 4-7 und 11-14)
Cumulative dose of rescue medication usedDuring the last four days of each study phase (days 4-7 und 11-14)
Subjective ratings of quality of life using the EQ-5D-5L questionnaireAt baseline and during each study phase (days 1-7 and days 8-14)
Minimum pain using the Brief Pain Inventory (BPI)During the last four days of each study phase(days 4-7 und 11-14)
Percentage increase in pain compared to baselineDuring 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 functioning using the Brief Pain Inventory (BPI) and the EQ-5D-5L questionnaireAt 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 preferenceAt day 7 and 14

Study vs. baseline

Participant's impression of changeAt 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 eventsDuring each study phase (days 1-7 and days 8-14)
Assessment of specific adverse events: nausea/vomitingDuring each study phase (days 1-7 and days 8-14)
Assessment of specific adverse events: drowsinessDuring whole study (days 1-14)
Assessment of specific adverse events: appetiteDuring each study phase (days 1-7 and days 8-14)
Assessment of specific adverse events: constipationDuring each study phase (days 1-7 and days 8-14)
Assessment of other adverse eventsDuring each study phase (days 1-7 and days 8-14)
Number of withdrawals from study or treatmentDuring each study phase (days 1-7 and days 8-14)
Time (days) of stable pain controlDuring whole study (days 1-14)
Patients' potential to develop hepatotoxicity (investigation of risk factors)During whole study (days 1-14)
% hours with pain/24hOn each study day, up to 14 days
Number of rescue medication usedDuring the last four days of each study phase (days 4-7 und 11-14)
Average pain using the Brief Pain Inventory (BPI)During the last four days of each study phase (days 4-7 und 11-14)
Current pain using the Brief Pain Inventory (BPI)During the last four days of each study phase (days 4-7 und 11-14)
Percentage of patients meeting the predefined pain thresholdDuring each study phase (days 1-7 and days 8-14)

Trial Locations

Locations (2)

Kantonsspital Baden

🇨🇭

Baden, Switzerland

Inselspital, Bern University Hospital

🇨🇭

Bern, Switzerland

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