Predel HG, Ebel-Bitoun C, Lange R, et al. A randomized, placebo- and active-controlled, multi-country, multi-center parallel group trial to evaluate the efficacy and safety of a fixed-dose combination of 400 mg ibuprofen and 100 mg caffeine compared with ibuprofen 400 mg and placebo in patients with acute lower back or neck pain. J Pain Res. 2019 Sep 23;12:2771-2783. doi: 10.2147/JPR.S217045. eCollection 2019. (Original study)

Background: Ibuprofen is a well-established analgesic for acute pain symptoms. In several acute pain models, caffeine has demonstrated an analgesic adjuvant effect. This randomized trial (NCT03003000) was designed to compare the efficacy of a fixed-dose combination of ibuprofen and caffeine with ibuprofen or placebo for the treatment of acute lower back/neck pain.

Methods: Patients with acute lower back/neck pain resulting in pain on movement (POM) =5 on a 10-point numerical rating scale were randomized 2:2:1 to receive orally, three times daily for 6 days, 400 mg ibuprofen+100 mg caffeine, 400 mg ibuprofen or placebo, respectively. The primary endpoint was change in POMWP (POM triggering highest pain score at baseline [worst procedure]) between baseline and the morning of day 2. Key secondary endpoints included POMWP area under curve (AUC) between baseline and the morning of day 4 (POMWPAUC72h) and day 6 (POMWPAUC120h).

Results: In total, 635 patients were randomized (256 ibuprofen + caffeine: 253 ibuprofen: 126 placebo). Active treatments exhibited similar reductions in POMWP, with an adjusted mean reduction of 1.998 (standard error [SE]: 0.1042) between baseline and day 2 for ibuprofen, 1.869 (SE: 0.1030) for ibuprofen + caffeine and 1.712 (SE: 0.1422) for placebo. Similar results were observed for POMWPAUC72h and POMWPAUC120h. Safety and tolerability was as expected.

Conclusion: A decrease in lower back/neck pain, indicated by reduced POMWP, was shown in all active treatment arms; however, treatment effects were small versus placebo. Ibuprofen plus caffeine was not superior to ibuprofen alone or placebo for the treatment of acute lower back/neck pain in this setting.

Related DynaMed Topics

Discipline Area Score
Family Medicine (FM)/General Practice (GP) 6 / 7
General Internal Medicine-Primary Care(US) 6 / 7
Special Interest - Pain -- Physician 5 / 7
Comments from MORE raters

Family Medicine (FM)/General Practice (GP) rater

With the daily onslaught of patients with acute (and acute on chronic) back pain, I suspect many physicians forget that placebo works nearly as well as active treatment. I'd fault this study for not using a more robust dose of Ibuprofen with more frequent dosing, but nevertheless, treatment effects were similar and minimal.

General Internal Medicine-Primary Care(US) rater

This is a randomized control trial with placebo vs. the other two arms and no difference in pain control. This is a great study highlighting the natural history of acute low back or neck pain.
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