Efficacy of Metamizole Versus Ibuprofen and a Short Educational Intervention Versus Standard Care in Acute Low Back Pain — EMISI  

Low Back Pain Clinical Trial

Official title: Efficacy of Metamizole Versus Ibuprofen and a Short Educational Intervention Versus Standard Care in Acute and Subacute Low Back Pain: A Randomized, Factorial Trial

Status Recruiting

Clinical Trial Summary

The EMISI trial is a randomized, double blind, controlled trial (RCT) using a factorial design in patients with a new low back pain episode. The study aims to assess (A) whether metamizole, a non-opioid drug approved in Switzerland for pain treatment, is non-inferior to ibuprofen in a new episode of acute or subacute LBP and (B) whether a short educational intervention including evidence-based patient information is superior to usual care alone. Despite its increased use, the role of metamizole for the treatment of LBP is unclear and has so far not been systematically studied.

Clinical Trial Description

Purpose Low back pain (LBP) is among the top three most common diseases worldwide resulting in a life with pain-related disability. In patients with persistent LBP over 3 months, the risk for chronic pain increases dramatically and effective interventions should aim to prevent pain persistence without overtreatment. Therefore, during an acute LBP episode, the most common recommendations are to use pain medication to alleviate pain and to keep patients physically active. Non-opioid and opioid pain medication is increasingly used to control pain. Despite the frequency of LBP, only few high-quality studies assessed the efficacy of pain medication. Since the 1990s, the use of opioid pain medication for non-cancer pain has soared and resulted in an epidemic of opioid dependence and abuse in the U.S. This, despite the fact that randomized clinical trials found little or no additional efficacy of opioids compared to non-opioid medication in LBP. Moreover, opioids are associated with potentially severe side-effects, including confusion, sedation, respiratory depression and dependence. Therefore, non-opioid pain medications that are safe and effective are urgently needed to control pain.

Non-steroidal anti-inflammatory drugs (NSAIDs) are considered to be effective for LBP and recommended by guidelines. However, adverse events including kidney injury and gastrointestinal bleeding, limit the use of NSAIDs in many patients. Metamizole is an effective non-opioid analgesic and antipyretic with a favorable gastrointestinal and renal safety profile and therefore, a valuable treatment option in many LBP patients with contraindications for NSAIDs. Metamizole has been increasingly used in many countries such as Germany, France, Spain, and Switzerland. Despite its increased use, the role of metamizole for the treatment of LBP is unclear and has so far not been systematically studied. This surprising lack of efficacy data may be due to an ongoing controversy over the risk of metamizole-associated agranulocytosis, a serious hematological adverse event. Even though the overall risk of agranulocytosis is increased compared to other drugs, it only occurs in a small proportion of susceptible patients and the overall safety profile of metamizole is still favorable compared to other analgesics such as NSAIDs or opioids, which carry their own specific risks.

Many patients have reservations against regular intake of pain medication and limit physical activity to keep pain manageable without medication, which is against the guidelines' recommendation. However, education to encourage activity may help to improve pain control and function as well. In a busy primary care practice extended educational sessions that have been shown to be effective are not feasible. A short educational intervention that provides evidence-based information on the nature of LBP and promotes physical activity may also improve outcome.

Objectives This study aims to assess (A) whether metamizole is non-inferior to ibuprofen in a new episode of acute or subacute LBP and (B) whether a short educational intervention including evidence-based patient information is superior to usual care alone.

Methods The EMISI trial is a randomized, double-blind, controlled trial (RCT) using a factorial design recruiting patients consulting general practitioners (GP) practices and the outpatient Division of the Department of General Internal Medicine at the University Hospital Bern, Switzerland. Patients are randomized into one of four groups (1:1:1:1): metamizole + educational intervention vs. metamizole + standard care vs. ibuprofen + educational intervention vs. ibuprofen + standard care. Patients assigned to the educational information will receive an information leaflet and a phone call by a member of the research team to discuss evidence based information on LBP. All patients will receive usual care provided by their GPs that includes additional pain medications and non-pharmacological measures at the GPs discretion.

The primary outcome (A) Comparison of ibuprofen vs. metamizole: change from baseline pain on the numeric rating scale (NRS) to day 14 (non-inferiority).

B) Comparison of the short intervention vs. usual care: change from baseline Core Outcome Measures Index (COMI) sum-score to 42 days follow-up (superiority).

Statistical analysis Analysis will include an intention-to-treat (ITT) and a per-protocol (PP) analysis for the comparison of the primary between metamizole and ibuprofen outcome (NRS change from baseline to follow-up at 14 days). Both analyses need to meet non-inferiority in order to claim success. The comparison of the primary outcome between the intervention and the usual care group (COMI change from baseline to day 42) will be performed according to intention-to-treat principle. Based on the sample size calculation for both interventions, 120 patients will be included into the study. ;

Related Conditions & MeSH terms

• Back Pain
• Low Back Pain

• NCT number: NCT04111315
• Study type: Interventional
• Source: Insel Gruppe AG, University Hospital Bern
• Contact: Maria M. Wertli, MD PhD
• Phone: +41796576420
• Email: Maria.Wertli@insel.ch
• Status: Recruiting
• Phase: Phase 4
• Start date: December 15, 2019
• Completion date: December 31, 2025