Efficacy of paracetamol added to WHO step III opioids in chronic pain control: study protocol for a randomised, double-blind, placebo-controlled, non-inferiority, multicentre study in Switzerland
Abstract
Introduction: The analgesic and antipyretic paracetamol (acetaminophen) is generally considered safe in therapeutic doses. The most important toxic effect is hepatotoxicity after supratherapeutic doses or in the presence of risk factors (eg, malnutrition, alcoholism). According to the WHO analgesic ladder, a combination of a non-opioid analgesic such as paracetamol with a strong opioid is recommended as step III treatment of patients with chronic pain, despite limited evidence for this approach. The main aim of this study is to test the hypothesis that paracetamol does not provide clinically relevant benefits when added to strong opioids in patients with chronic pain.
Methods and analysis: Investigator-initiated, randomised, double-blind, placebo-controlled, non-inferiority trial at two Swiss hospitals. A total of 140 patients with chronic pain requiring strong opioids and paracetamol ≥1.5 g/day for at least 7 days will be enrolled and randomised to either continued combination treatment or strong opioid plus placebo. In the first study phase (days 1-7), patients receive identically looking capsules containing either paracetamol at the exact dose previously used or a placebo. During a second study phase (days 7-14), all patients stop the blinded study medication (paracetamol and placebo) with follow-up to day 14. Adherence will be assessed by pill count and measurement of paracetamol and opioid serum concentrations. Patients are instructed to use a pain diary daily during…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 140 participants or records.
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