Paracetamol for Acute Low Back Pain

The aim of this thesis was 1) to describe the similarities and differences between recommendations for pharmacotherapy of low back pain (LBP) from recent clinical practice guidelines; 2) to investigate if the results and inferences from the Paracetamol for Acute Low Back Pain (PACE) trial could be reproduced; 3) to assess the efficacy of paracetamol for acute non-specific LBP in participants of the PACE trial who complied with the treatment regimen; and 4) to investigate if there is an association between reporting adverse events (AEs) and the outcomes of acute LBP

Paracetamol for low back pain: the state of the research field

Introduction: Paracetamol is one of the most frequently used analgesics for people with low back pain, but despite its frequent use there is still debate regarding its efficacy and safety for this indication. Areas covered: We describe the origin of paracetamol and its proposed mechanisms of action. We focus in on low back pain and describe the evidence it has on the efficacy of paracetamol (taken by patients orally) and current insights on its side-effects. When searching for relevant publications we focused mainly on recent Cochrane reviews and published RCTs. We found that there is increasing evidence that shows paracetamol is not more effective than placebo in patients with acute low back pain. Concerning patients with subacute and chronic back pain, the evidence for or against the efficacy of paracetamol vs placebo is lacking and would need more research. Expert opinion: We argue that we still need better evidence on the efficacy of paracetamol for acute and chronic back pain. Until that evidence becomes available paracetamol should still be considered as an option for patients with back pain. However, we suggest that a strategy focusing on nonpharmacological management as the first treatment option in low back pain may be equally effective with less side effects

Inferential reproduction analysis demonstrated that “paracetamol for acute low back pain” trial conclusions were reproducible

Objectives: The aim of this study was to reanalyze and reinterpret data obtained in Paracetamol in Acute Low Back Pain (PACE), the first large randomized controlled trial evaluating the efficacy of paracetamol in acute low back pain, to assess the inferential reproducibility of the original conclusions. Study Design and Setting: Mixed effects models were used to reanalyze pain intensity (primary outcome; 11-point Numeric Rating Scale) and physical functioning, health-related quality of life, sleep quality, and time until recovery (as secondary outcomes), according to the intention-to-treat principle. The original authors of the PACE study were not involved in the development of the methods for this reanalysis. Results: The reproduction analyses indicated no effect of treatment on pain intensity and confidence intervals excluded clinically worthwhile effects (adjusted main effect for regular paracetamol vs. placebo 0.00 [−0.02, 0.01; P = 0.85]; adjusted main effect for paracetamol as-needed vs. placebo 0.00 [−0.02, 0.01; P = 0.92]). Similar results were obtained for all secondary outcomes. Conclusion: This study indicates that the conclusions of the PACE trial are inferentially reproducible, even when using a different analytical approach. This reinforces the notion that the management of acute low back pain should focus on providing patients advice and reassurance without the addition of paracetamol

Efficacy of paracetamol, diclofenac and advice for acute low back pain in general practice: design of a randomized controlled trial (PACE Plus)

Background: Low back pain is common and associated with a considerable burden to patients and society. There is uncertainty regarding the relative benefit of paracetamol and diclofenac and regarding the additional effect of pain medication compared with advice only in patients with acute low back pain. This trial will assess the effectiveness of paracetamol, diclofenac and placebo for acute low back pain over a period of 4 weeks. Furthermore, this trial will assess the additional effectiveness of paracetamol, diclofenac and placebo compared with advice only for acute low back pain over a period of 4 weeks. Methods: The PACE Plus trial is a multi-center, placebo-blinded, superiority randomized controlled trial in primary care, with a follow-up of 12 weeks. Patients with acute low back pain aged 18-60 years presenting in general practice will be included. Patients are randomized into four groups: 1) Advice only (usual care conforming with the clinical guideline of the Dutch College of General Practitioners); 2) Advice and paracetamol; 3) Advice and diclofenac; 4) Advice and placebo. The primary outcome is low back pain intensity measured with a numerical rating scale (0-10). Secondary outcomes include compliance to treatment, disability, perceived recovery, costs, adverse reactions, satisfaction, sleep quality, co-interventions and adequacy of blinding. Between group differences for low back pain intensity will be evaluated using a repeated measurements analysis with linear effects models. An economic evaluation will be performed using a cost-effectiveness analysis with low back pain intensity and a cost-utility analysis with quality of life. Explorative analyses will be performed to assess effect modification by predefined variables. Ethical approval has been granted. Trial results will be released to an appropriate peer-viewed journal. Discussion: This paper presents the design of the PACE Plus trial: a multi-center, placebo-blinded, superiority randomized controlled trial in primary care that will assess the effectiveness of advice only, paracetamol, diclofenac and placebo for acute low back pain. Trial registration: Dutch Trial Registration NTR6089 , registered September 14th, 2016. Protocol: Version 4, June 2016

Discontinuation of the PACE Plus trial: Problems in patient recruitment in general practice

Background: The PACE Plus trial was a multi-center, double-blinded, superiority randomized controlled trial (RCT) conducted in patients from Dutch general practice to investigate the efficacy of paracetamol and NSAIDs in acute non-specific low back pain (LBP). Because insufficient numbers of patients could be recruited (only four out of the required 800 patients could be recruited over a period of 6 months), the trial was prematurely terminated in February 2017, 6 months after the start of recruitment. This article aims to transparently communicate the discontinuation of PACE Plus and to make recommendations for future studies. Methods: General Practitioners (GPs) from 36 participating practices received a one-question survey in which they were asked to give the three most important factors that in their opinion contributed to failure of patient recruitment. Results: GPs of 33 out of 36 (92%) participating practices sent a response. A total of 81 factors were reported. These have been categorized into patient factors (26 out of 81 comments, 32%), GP factors (39 out of 81 comments, 48%) and research factors (16 out of 8