Clinical trial NCT05051735: PARASTOP - Paracetamol With Strong Opioids
Official title: PARASTOP - Paracetamol With Strong Opioids. A Randomized, Double-blind, Parallel-group Non-inferiority Phase III Withdrawal Trial of Paracetamol Versus Placebo in Conjunction With Opioids for Moderate to Severe Cancer-related Pain
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Cancer Pain
Cancer
Keywords: Cancer Pain
Pain
Analgesics
Sensory System Agents
Physiological Effects of Drugs
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: Sykehuset Telemark
First posted: 2021-09-21
Enrollment: 204
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: Current guidelines recommend all people with cancer-related pain should be prescribed paracetamol, even those receiving high doses of strong pain killers (opioids) such as morphine. Although this has been shown in studies to be beneficial in other conditions, for instance dental work and after surgery, it has not been shown to further improve pain in people with cancer-related pain. Taking tablets is burdensome to patients and the study aims to determine whether the inconvenience of taking eight extra paracetamol tablets per day can be justified.

The study plans to show whether or not pain control is changed (non-inferior) when stopping paracetamol compared to continued use of paracetamol in people already taking strong pain killers for cancer-related pain. Voluntary participants who are taking a combination of paracetamol and a strong opioid are recruited to the study.


Eligibility criteria: Inclusion Criteria:

* Participants must be ≥ 18 years of age inclusive, at the time of signing the informed consent.
* ≥50 kg (due to paracetamol dosage)
* Participants who are under palliative care or oncology service review
* Diagnosis of metastatic cancer
* Clinician-predicted life expectancy \>2 months
* Receiving daily regular strong opioids for cancer pain
* Receiving stable scheduled opioid dose last 48 hours\*
* Receiving paracetamol 1 gram x three or four times a day for at least five days
* Average pain intensity past 24 hours ≥ 2 and ≤ 7 (NRS 0-10)\*
* Able to take study drug/placebo as tablets
* Able to comply with all study procedures
* Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

  * It is allowed to repeat procedure within the screening period without considering the participant being a rescreen

Exclusion Criteria:

* History of allergy or hypersensitivity to any of the active substances or excipients in the study drug
* Known severe liver or renal failure equivalent with CTCAE Grade 3 or 4\* precluding continuation of paracetamol. (\*Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0)
* Participants receiving subcutaneous, intravenous, intrathecal, or epidural opioid therapy
* Participants receiving systemic anticancer treatment during the intervention period if they are anticipated to have increasing pain or other symptoms related to the treatment
* Co-enrolment in other drug trials. Participants will not be enrolled in any other on-going interventional clinical trial. Study participants may be enrolled in non-interventional research (e.g. questionnaire, tissue collection studies)
* Previously enrolled in this study
* Pregnant or lactating women

Primary outcomes:
measure: To establish whether placebo with strong opioids compared to paracetamol together with strong opioids provides non-inferior analgesia for cancer-related pain.
timeFrame: 7 days
Secondary outcomes:
measure: To establish whether placebo with strong opioids compared to paracetamol with strong opioids changes opioid related side effects.
timeFrame: 7 days
measure: To establish whether placebo with strong opioids compared to paracetamol with strong opioids changes global rating of improvement.
timeFrame: 7 days
measure: To establish whether placebo with strong opioids compared to paracetamol with strong opioids changes opioid requirements.
timeFrame: 7 days
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Sarpsborg
country: Norway
facility: Østfold Hospital Trust
state: Grålum
city: Drammen
country: Norway
facility: Vestre Viken Hospital Trust
city: Førde
country: Norway
facility: Førde Hospital Trust
city: Kristiansand
country: Norway
facility: Sørlandet Hospital Trust
city: Lørenskog
country: Norway
facility: Akershus University Hospital
city: Oslo
country: Norway
facility: OsloUH
city: Skien
country: Norway
facility: Telemark Hospital Trust
city: Stavanger
country: Norway
facility: Stavanger University Hospital
city: Tromsø
country: Norway
facility: Universitetssykehuset Nord-Norge
city: Trondheim
country: Norway
facility: St. Olavs Hospital
city: Tønsberg
country: Norway
facility: Vestfold Hospital trust
city: Ålesund
country: Norway
facility: Helse Møre og Romsdal
city: Kampala
country: Uganda
facility: Makere University Hospital
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Research
Study officials:
affiliation: Telemark Hospital Trust
name: Ørnulf Paulsen
role: PRINCIPAL_INVESTIGATOR
References: