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

Abstract

BackgroundLow 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.MethodsThe 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.DiscussionThis 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 registrationDutch Trial Registration NTR6089, registered September 14th, 2016. Protocol: Version 4, June 2016.

Diclofenac attenuates inflammation through TLR4 pathway and improves exercise performance after exhaustive swimming

“…17 In some countries, diclofenac has been the most commonly prescribed NSAID over the past decade. 18 Furthermore, recent results of our research group demonstrate that acute eccentric exercise increased TLR4-mediated NF-κB activation in liver from rats pretreated with diclofenac and leads to an augmented expression of different pro-inflammatory genes, highlighting the role of TLR4 as a target for anti-inflammatory interventions in liver diseases. 19 The present study aimed to verify the effects of diclofenac administration on time to exhaustion and liver inflammatory and redox markers in rats submitted to consecutive and exhaustive swimming bouts.…”

“…The adaptation consisted in keeping the animals in shallow water (5 cm in depth) at 31 ± 1°C between 9 and 11 hours am in a tank of 80 cm in length, 50 cm in width, and 90 cm in depth. 18 A total of 24 animals were randomly allocated and divided into sedentary-saline (n = 4) and sedentary-diclofenac (n = 4) groups to verify diclofenac per se effects, and to test the effects of diclofenac on exhaustive exercise bouts we subdivided the animals into exhaustion-saline (n = 7) and exhaustion-diclofenac (n = 7) groups. Rats from both groups performed three repeated exhaustive swimming bouts with each bout separated by a 72-h time period.…”

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

“…Unfortunately, a subsequent attempt to replicate the PACE-trial, namely the PACE-plus trial was discontinued due to problems with patient recruitment [37]. It was however, possible to conduct a re-analysis of the original data of the PACE study using the predefined and published protocol of the PACE-plus study, including its statistical analysis plan [39]. In this so-called inferential reproducibility study, conducted by an independent group, a different primary outcome was chosen, namely pain intensity (0-10 NRS), data from pain diaries were used instead of data from follow-up questionnaires, a different statistical approach was used and preplanned exploratory subgroup analyses (based on severe pain intensity NRS >7 and severe impairment of physical functioning (RMDQ > 16)) were included.…”

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

“…The PACE Plus trial was conducted in Dutch general practice to investigate the efficacy of paracetamol and NSAIDs in acute non-specific low back pain (LBP) [ 1 ]. The study design was a multi-center, placebo-blinded, superiority randomized controlled trial (RCT).…”

“…The two main aims of this RCT were to replicate the comparison between paracetamol and placebo as done in the PACE trial [ 2 – 4 ] and to compare the efficacy of paracetamol with diclofenac and advice only. The study protocol was published [ 1 ] and was prospectively registered (Dutch Trial Registration NTR6089, registered September 14th 2016). The Erasmus MC Medical Research and Ethics Committee (MREC) has granted approval for the PACE Plus trial (NL54941.078.16).…”