PARASTOP - Paracetamol With Strong Opioids (PARASTOP)

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

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.

Study Overview

• Status: Completed
• Conditions: Cancer; Cancer Pain
• Intervention / Treatment: Drug: Placebo; Drug: Paracetamol

• Study Type: Interventional
• Enrollment (Actual): 204
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy
    • Fondazione IRCCS Istituto Nazionale dei Tumori
• Norway
  • Lørenskog, Norway, 1478
    • Akershus University Hospital
  • Oslo, Norway, 0424
    • OsloUH
  • Skien, Norway
    • Telemark Hospital Trust
  • Tromsø, Norway, 9019
    • Universitetssykehuset Nord-Norge
  • Trondheim, Norway, 7030
    • St. Olavs Hospital
  • Tønsberg, Norway, 3103
    • Vestfold Hospital Trust
  • Ålesund, Norway, 6026
    • Helse Møre og Romsdal
  • Drammen
    • Drammen, Drammen, Norway, 3004
      • Vestre Viken Hospital Trust
  • Førde
    • Førde, Førde, Norway, 6812
      • Førde Hospital Trust
  • Grålum
    • Sarpsborg, Grålum, Norway, 1714
      • Østfold Hospital Trust
  • Kristiansand
    • Kristiansand, Kristiansand, Norway, 4604
      • Sørlandet Hospital Trust
  • Stavanger
    • Stavanger, Stavanger, Norway, 4011
      • Stavanger University Hospital
• Uganda
  • Kampala, Uganda
    • Makere University Hospital
• United Kingdom
  • Edinburgh, United Kingdom
    • Edinburgh Cancer Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Paracetamol; Paracetamol P.O. 500 mg 2 tablets four times a day for 7 days	Drug: Paracetamol; Paracetamol 500 mg; Other Names: Acetaminophen
Placebo Comparator: Placebo; Placebo P.O. 2 tablets four times a day for 7 days	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To establish whether placebo with strong opioids compared to paracetamol together with strong opioids provides non-inferior analgesia for cancer-related pain.	Numeric Rating Scale 0-10: Average pain intensity past 24 hours	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To establish whether placebo with strong opioids compared to paracetamol with strong opioids changes opioid related side effects.	Opioid Side Effects Questionnaire	7 days
To establish whether placebo with strong opioids compared to paracetamol with strong opioids changes global rating of improvement.	Patient Global Impression of Change	7 days
To establish whether placebo with strong opioids compared to paracetamol with strong opioids changes opioid requirements.	Opioid consumption	7 days

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: Sykehuset Telemark
• Investigators: Principal Investigator: Ørnulf Paulsen, Telemark Hospital Trust

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2021
• Primary Completion (Actual): February 11, 2026
• Study Completion (Actual): February 18, 2026

Study Registration Dates

• First Submitted: September 11, 2021
• First Submitted That Met QC Criteria: September 20, 2021
• First Posted (Actual): September 21, 2021

Study Record Updates

• Last Update Posted (Actual): February 25, 2026
• Last Update Submitted That Met QC Criteria: February 23, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Pain; Physiological Effects of Drugs; Cancer Pain; Sensory System Agents; Analgesics
• Additional Relevant MeSH Terms: Neurologic Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Cancer Pain; Pain; Neoplasms; Organic Chemicals; Anilides; Amides; Aniline Compounds; Amines; Acetanilides; Acetaminophen
• Other Study ID Numbers: 180946

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No