Efficacy of antibiotic treatment in patients with chronic low back pain and Modic changes (the AIM study): double blind, randomised, placebo controlled, multicentre trial

Lars Christian Haugli Bråten, Mads Peder Rolfsen, Ansgar Espeland, Monica Wigemyr, Jörg Aßmus, Anne Froholdt, Anne Julsrud Haugen, Gunn Hege Marchand, Per Martin Kristoffersen, Olav Lutro, Sigrun Randen, Maja Wilhelmsen, Bendik Slagsvold Winsvold, Thomas Istvan Kadar, Thor Einar Holmgard, Maria Dehli Vigeland, Nils Vetti, Øystein Petter Nygaard, Benedicte Alexandra Lie, Christian Hellum, Audny Anke, Margreth Grotle, Elina Iordanova Schistad, Jan Sture Skouen, Lars Grøvle, Jens Ivar Brox, John-Anker Zwart, Kjersti Storheim, AIM study group, Lars Christian Haugli Bråten, Mads Peder Rolfsen, Ansgar Espeland, Monica Wigemyr, Jörg Aßmus, Anne Froholdt, Anne Julsrud Haugen, Gunn Hege Marchand, Per Martin Kristoffersen, Olav Lutro, Sigrun Randen, Maja Wilhelmsen, Bendik Slagsvold Winsvold, Thomas Istvan Kadar, Thor Einar Holmgard, Maria Dehli Vigeland, Nils Vetti, Øystein Petter Nygaard, Benedicte Alexandra Lie, Christian Hellum, Audny Anke, Margreth Grotle, Elina Iordanova Schistad, Jan Sture Skouen, Lars Grøvle, Jens Ivar Brox, John-Anker Zwart, Kjersti Storheim, AIM study group

Abstract

Objective: To assess the efficacy of three months of antibiotic treatment compared with placebo in patients with chronic low back pain, previous disc herniation, and vertebral endplate changes (Modic changes).

Design: Double blind, parallel group, placebo controlled, multicentre trial.

Setting: Hospital outpatient clinics at six hospitals in Norway.

Participants: 180 patients with chronic low back pain, previous disc herniation, and type 1 (n=118) or type 2 (n=62) Modic changes enrolled from June 2015 to September 2017.

Interventions: Patients were randomised to three months of oral treatment with either 750 mg amoxicillin or placebo three times daily. The allocation sequence was concealed by using a computer generated number on the prescription.

Main outcome measures: The primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (range 0-24) at one year follow-up in the intention to treat population. The minimal clinically important between group difference in mean RMDQ score was predefined as 4.

Results: In the primary analysis of the total cohort at one year, the difference in the mean RMDQ score between the amoxicillin group and the placebo group was -1.6 (95% confidence interval -3.1 to 0.0, P=0.04). In the secondary analysis, the difference in the mean RMDQ score between the groups was -2.3 (-4.2 to-0.4, P=0.02) for patients with type 1 Modic changes and -0.1 (-2.7 to 2.6, P=0.95) for patients with type 2 Modic changes. Fifty patients (56%) in the amoxicillin group experienced at least one drug related adverse event compared with 31 (34%) in the placebo group.

Conclusions: In this study on patients with chronic low back pain and Modic changes at the level of a previous disc herniation, three months of treatment with amoxicillin did not provide a clinically important benefit compared with placebo. Secondary analyses and sensitivity analyses supported this finding. Therefore, our results do not support the use of antibiotic treatment for chronic low back pain and Modic changes.

Trial registration: ClinicalTrials.gov NCT02323412.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from governmental organisations Helse Sør-Øst and Helse Vest for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Figures

Fig 1
Fig 1
Flowchart showing trial group assignments, loss to follow-up, treatment completion, and protocol deviations. RMDQ=Roland-Morris Disability Questionnaire. *One patient in amoxicillin group and one patient in placebo group became pregnant (protocol deviation because all patients were instructed to use contraception), not included in per protocol population. †Three patients in amoxicillin group stopped study drug because of adverse events and were included in per protocol population. ‡One patient in amoxicillin group stopped study drug because of adverse events but was not included in per protocol population owing to poor compliance before stopping study drug. §Two patients in placebo group discontinued because they started three month treatment with amoxicillin plus clavulanic acid. ¶Treated with apocillin seven days before randomisation. **Because of a mistake at pharmacy, patient was given a mix of bottles containing amoxicillin and placebo. ††Treated with cephalexin seven days before randomisation.
Fig 2
Fig 2
Roland-Morris Disability Questionnaire score and low back pain intensity (numerical rating scale) from baseline to one year
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6812614/bin/bral050262.va.jpg

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