PARASTOP - Paracetamol With Strong Opioids

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Cancer Pain, Cancer

Intervention / Treatment
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* Drug: Paracetamol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paracetamol<br>Paracetamol P.O. 500 mg 2 tablets four times a day for 7 days | Drug: Paracetamol<br>* Paracetamol 500 mg<br>* Other names: Acetaminophen;|
| Placebo Comparator: Placebo<br>Placebo P.O. 2 tablets four times a day for 7 days | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer Pain, Pain, Analgesics, Sensory System Agents, Physiological Effects of Drugs