A cluster randomized trial to measure the impact on nonsteroidal anti-inflammatory drug and proton pump inhibitor prescribing in Italy of distributing cost-free paracetamol to osteoarthritic patients

Sara Di Pede,Massimo Vicentini,Alessandra Ferretti,Alberto Gandolfi,Corrado Busani,Daniela Riccò,Paolo Giorgi Rossi,Daniela Zoboli,Pamela Mancuso,Morena Pellati

doi:10.1186/s12875-019-1050-4

Abstract

BackgroundParacetamol is recommended as first-line treatment for pain control in osteoarthritis because it has fewer side effects than do other therapeutic options, including nonsteroidal anti-inflammatory drugs (NSAIDs). Prescribing proton pump inhibitors (PPIs) as gastric bleeding prophylaxis in chronic NSAID users is also common, although not recommended. In Italy, paracetamol is not reimbursed by the National Health System. The aim of this trial was to test whether the availability to osteoarthritis patients of free paracetamol would decrease their use of NSAIDs and, as a secondary objective, whether opioid and PPI consumption would also decrease.MethodsEight general practitioners (GPs) (59 patients) were randomized to usual care and 8 (58 patients) to the experimental arm, where prescribed paracetamol was directly distributed for free by the local hospital. After 6 months, paracetamol was also available for free in the control arm.The main outcome was the pre/post difference in average NSAID and PPI consumption. Differences between experimental and control arms in pre/post differences are reported, as registered by the drug prescription information system.ResultsAverage NSAID consumption decreased non-significantly, from 6.79 to 2.16 defined daily dose (DDD) in the experimental arm and from 3.19 to 2.97 DDD in the control group (p = 0.067). No changes were observed for PPIs (from 11.27 to 14.65 DDD and from 9.74 to 12.58 DDD in experimental and control arms, respectively, p = 0.788) or opioids (from 1.61 to 1.14 DDD and from 1.41 to 1.56 DDD in experimental and control arms, respectively, p = 0.419). When the intervention was extended to the control arm, no decrease in NSAID consumption was observed (from 2.46 to 2.43 DDD, p = 0.521).ConclusionsRemoving small economic barriers had small or no effect on the appropriateness of opioid or PPI prescribing to patients with osteoarthritis; a reduction in NSAID consumption cannot be ruled out.Trial registration numberNCT02691754 (Approved February 24, 2016).

Highlights

Paracetamol is recommended as first-line treatment for pain control in osteoarthritis because it has fewer side effects than do other therapeutic options, including nonsteroidal anti-inflammatory drugs (NSAIDs)
Despite doubts on the effectiveness of paracetamol in the treatment of pain in osteoarthritis described in a recent meta-analysis, [2] many European and American guidelines recommend its use at high dose, (3 g/day) as a first-line drug for pain control because it is safer than other first-line options [3,4,5,6]
One General Practitioner (GP), in the control arm, stated he had not seen any patient with osteoarthritis during the study period

Summary

Introduction

Paracetamol is recommended as first-line treatment for pain control in osteoarthritis because it has fewer side effects than do other therapeutic options, including nonsteroidal anti-inflammatory drugs (NSAIDs). Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective for pain control in osteoarthritis, with both analgesic and anti-inflammatory action, but they have adverse gastric, renal, and cardiac effects, in older patients who are at high risk of NSAID-induced gastroduodenal lesions [7,8,9]. For this reason, most guidelines recommend NSAIDs only as second-line treatment, alone or in association with paracetamol [3, 5, 6]. NSAIDs are often prescribed in association with gastroprotective drugs, in particular proton pump inhibitors (PPIs) even if prophylactic use of PPI is not recommended [3]

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