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

Pain Clinical Trial

— ParOP  

Official title:

Paracetamol in Addition to WHO Step III Opioids in Chronic Cancer Pain Control - a Randomized, Double-blind, Placebo-controlled, Non-inferiority Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05088876
• Other study ID #: BASEC-ID: 2021-01518
• Status: Recruiting
• Phase: Phase 4
• Start date: August 30, 2024
• Est. completion date: December 1, 2024

Study information

• Verified date: June 2024
• Source: Insel Gruppe AG, University Hospital Bern
• Contact: Evangelia Liakoni
• Phone: 0041316325461
• Email: evangelia.liakoni[@]insel.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Blinded withdrawal of regular co-medication with paracetamol in chronic pain patients under strong opioids on pain control.

Description:

Chronic pain cancer 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. Between the on-site visits, patients will be followed up by phone calls on day 3 (±1d) and day 10 (±1d). 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 information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: December 1, 2024
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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

Related Conditions & MeSH terms

• Cancer Pain
• Pain

Intervention

Drug:
• Placebo
Blinded withdrawal of regular co-medication with paracetamol
• Paracetamol
Paracetamol in the dose already used

Locations

Country	Name	City	State
Switzerland	Kantonsspital Baden	Baden
Switzerland	Inselspital, Bern University Hospital	Bern

Sponsors (2)

Lead Sponsor	Collaborator
Insel Gruppe AG, University Hospital Bern	Swiss National Science Foundation

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	VAS score (average pain intensity)		Study day 7
Secondary	Average pain using the Brief Pain Inventory (BPI)		On each study day, up to 14 days
Secondary	Minimum pain using the Brief Pain Inventory (BPI)		On each study day, up to 14 days
Secondary	Worst pain using the Brief Pain Inventory (BPI)		On each study day, up to 14 days
Secondary	Current pain using the Brief Pain Inventory (BPI)		On each study day, up to 14 days
Secondary	Average pain using the Brief Pain Inventory (BPI)		During the last four days of each study phase (days 4-7 und 11-14)
Secondary	Minimum pain using the Brief Pain Inventory (BPI)		During the last four days of each study phase(days 4-7 und 11-14)
Secondary	Worst pain using the Brief Pain Inventory (BPI)		During the last four days of each study phase (days 4-7 und 11-14)
Secondary	Current pain using the Brief Pain Inventory (BPI)		During the last four days of each study phase (days 4-7 und 11-14)
Secondary	Cumulative dose of rescue medication used		On each study day, up to 14 days
Secondary	Cumulative dose of rescue medication used		During the last four days of each study phase (days 4-7 und 11-14)
Secondary	Number of rescue medication used		On each study day, up to 14 days
Secondary	Number of rescue medication used		During the last four days of each study phase (days 4-7 und 11-14)
Secondary	Percentage increase in pain compared to baseline		During each study phase (days 1-7 and days 8-14)
Secondary	Percentage of patients meeting the predefined pain threshold		During each study phase (days 1-7 and days 8-14)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)	Prior to study treatment
Secondary	Question about participant's preference	Study vs. baseline	At day 7 and 14
Secondary	Participant's impression of change	11-point scale tool between -5 ="very much worse" and +5 ="completely recovered"	At day 7 and 14
Secondary	Participants' guess regarding their assigned group (verum or placebo)		At day 7 and 14
Secondary	Assessment of serious adverse events		During each study phase (days 1-7 and days 8-14)
Secondary	Assessment of specific adverse events: nausea/vomiting		During each study phase (days 1-7 and days 8-14)
Secondary	Assessment of specific adverse events: drowsiness		During whole study (days 1-14)
Secondary	Assessment of specific adverse events: appetite		During each study phase (days 1-7 and days 8-14)
Secondary	Assessment of specific adverse events: constipation		During each study phase (days 1-7 and days 8-14)
Secondary	Assessment of other adverse events		During each study phase (days 1-7 and days 8-14)
Secondary	Number of withdrawals from study or treatment		During each study phase (days 1-7 and days 8-14)
Secondary	Time (days) of stable pain control		During whole study (days 1-14)
Secondary	Patients' potential to develop hepatotoxicity (investigation of risk factors)		During whole study (days 1-14)
Secondary	% hours with pain/24h		On each study day, up to 14 days