Methods

Randomised, actively controlled, multicentre, single‐blind study

Participants

Population source: 371 participants with acute non‐specific LBP of at least moderate pain intensity (133 participants randomised to paracetamol or placebo group). The study was conducted at 11 sites.

Inclusion criteria: Pain of moderate intensity (2 or more on a 6‐point scale), age 18 to 55 years (inclusive), ambulatory status, no low back trauma within the preceding 48 hours, and an answer of “yes” to the question “Do the muscles in your low back hurt?”

Exclusion criteria: Any evidence or history of radiculopathy or other neurologic deficits (e.g. abnormal straight‐leg‐raise test results, patellar reflexes, or bowel or bladder function), or a history of back surgery, fibromyalgia, diabetes mellitus, peripheral vascular disease, osteoporosis, gastrointestinal ulcers, gastrointestinal bleeding or perforation, renal disease, pulmonary oedema, cardiomyopathy, liver disease, intrinsic coagulation defects, bleeding diseases or anticoagulant therapy (e.g. warfarin), daily back pain for more than 3 consecutive months, or hypersensitivity to acetaminophen, non‐steroidal anti‐inflammatory drugs, or heat

Interventions

The intervention groups consisted of

1. heat wrap (ThermaCare Heat Wrap; Procter & Gamble, Cincinnati, OH), which wraps around the lumbar region of the torso and uses a velcro‐like closure, heats to 104 degrees F (40 degrees C) within 30 minutes of exposure to air, and maintains this temperature continuously for 8 hours of wear;

2. oral ibuprofen, 2 tablets 3 times daily for a total dose of 1200 mg, with oral placebo 1 time daily for blinding from the acetaminophen group;

3. oral acetaminophen, 2 tablets 4 times daily for a total of 4000 mg dose total;

4. oral placebo, 2 tablets 4 times daily; and

5. unheated back wrap.

All treatments were administered on 2 consecutive days

Outcomes

Primary: pain relief (NRS 0 to 5), disability (Roland Morris 0 to 24).

Secondary: safety.

Notes

Funding: This study was funded by the Procter & Gamble Company.

Conflicts of interest: Industry funds were received to support this work. 6 out of 8 study authors are employees of the Procter & Gamble Health Sciences Institute, and 1 author is a paid consultant for Procter & Gamble Company.

There is no information on the dates when the study was conducted

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "subjects were randomized to treatment by a ratio of 6:6:6:1:1".

Comment: Unclear

Allocation concealment (selection bias)

Unclear risk

Comment: Unclear

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Quote: "single (investigator) blind".

Comment: Unclear if blinding was done for the assessor or the care provider

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Quote: "single (investigator) blind".

Comment: Unclear if the assessor or the care provider was blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

9/113 not evaluable for primary efficacy variable in the intervention group; 1/20 not evaluable for primary efficacy variable in the control group

Selective reporting (reporting bias)

High risk

Comment: The placebo group is listed in the methods, but no data for this group are reported for any time point

Other bias

Unclear risk

Comment: Data for the placebo group are unavailable. This study received funds from a company that produces paracetamol

Methods

Multicentre, double‐dummy, randomised, placebo‐controlled trial

Participants

Population source: 1653 participants (acetaminophen n = 550, acetaminophen as required n = 546, placebo n = 547) recruited from primary care clinicians (general practitioners, pharmacists, or physiotherapists) across Sydney, Australia, screened consecutive people who sought care for LBP directly or in response to a community advertisement.

Inclusion criteria: A new episode of acute LBP (defined as pain between the 12th rib and buttock crease that was less than 6 weeks' duration and preceded by 1 month of no pain) with or without leg pain, and at least moderate‐intensity pain (measured by an adaptation of item 7 of the SF‐36).

Exclusion criteria: Suspected serious spinal pathology; currently using full regular recommended doses of an analgesic; spinal surgery in the preceding 6 months; contraindication to paracetamol; using psychotropic medication for a health condition deemed to prevent reliable recording of study information; or pregnant or planning pregnancy

Interventions

Participants were asked to take 2 types of tablets for up to 4 weeks: 2 tablets from the regular box every 6 to 8 hours (6 tablets per day), and 1 or 2 tablets from the as‐needed box when needed for pain relief (4 to 6 hours apart, to a maximum of 8 tablets per day). Participants in the regular group received 665 mg modified‐release paracetamol tablets in the regular box and placebo tablets in the as‐needed box. Participants in the as‐needed group received placebo tablets in the regular box and 500 mg paracetamol immediate‐release tablets in the as‐needed box. Participants in the placebo group received placebo tablets in both boxes

Outcomes

Pain (0 to 10), disability (Roland Morris 0 to 24), function (Patient‐Specific Functional Scale), quality of life (SF‐12), global impression of recovery (Global Perceived Effect scale), sleep quality, adherence, adverse events

Notes

Funding: National Health and Medical Research Council of Australia and GlaxoSmithKline Australia.

Conflicts of interest: One author received funding for a research scholarship
from GlaxoSmithKline, and another author received funding to review teaching
materials prepared by GlaxoSmithKline. The other authors declared no competing interests.

There is no information on the dates when the study was conducted

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "computer‐generated randomisation schedule".

Comment: Adequate

Allocation concealment (selection bias)

Low risk

Quote: "concealed random allocation"; "Research staff not involved in preparation of medicine boxes collected baseline information by telephone and instructed patients to open the box and begin treatment".

Comment: Adequate

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "Clinicians, participants, and staff collecting outcome data, assessing outcomes, and analysing data were masked to group allocation".

Comment: Adequate

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: "Clinicians, participants, and staff collecting outcome data, assessing outcomes, and analysing data were masked to group allocation".

Comment: Adequate

Incomplete outcome data (attrition bias)
All outcomes

Low risk

31/1099 withdrawn from intervention groups; 15/553 withdrawn from control group. The completeness of survival data, measured by the completeness index, was 94.4%

Selective reporting (reporting bias)

Low risk

All outcomes that are of interest in the review have been reported

Other bias

Low risk

This study was an investigator‐initiated trial that received supplementary funding from a pharmaceutical company and reported that the sponsor had no role in conducting the study or analysing the data. Given this background and the negative trial outcome, this study appears to be free of other sources of bias and met this criterion