Background Lidocaine infusions are used variably around Australia to treat people with neuropathic cancer pain. The LiCPAIN trial aimed to determine the feasibility of conducting a double-blind randomised controlled trial of continuous subcutaneous lidocaine for neuropathic cancer pain. The primary objective was

Methods Palliative care inpatients at 5 metropolitan NSW sites were randomised to a 72-hour continuous infusion of subcutaneous lidocaine or placebo at 1–2mg/kg/hr, capped at 120mg/kg/hr. Participants had cancer pain with neuropathic features, with a worst pain score of four out of ten or higher in the past 24 hours despite adequate trial of opioid and adjuvant analgesics. Exclusion criteria included increased risk of cardiac or neurological toxicity due to pre-existing conditions, altered metabolism and drug interactions. Efficacy and toxicity assessment informed infusion titration daily.

Results Seventeen participants were randomised out of 124 screened. The mean age was 64.1 years (SD=11.2) and 77% were female. The mean weight was 70.8kg (SD=23.3). The mean worst pain score at baseline was 7.8 (SD=1.2) with a mean daily oral morphine-equivalent regular opioid use was 189.2mg (SD=160.6).

The completion rate of study medication and procedures was 93% (95% confidence interval 5%) and 88% completed 72 hours of study medication. Four participants were randomised in the first eighteen months and it took 54 months to reach sample size.

There was no significant difference between the number of intervention and placebo participants who had a reduction of 1 or more points for worst pain on the BPI-SF (50% vs 57% p=0.77). The mean change in worst pain on the BPI-SF was –0.7 (SD=XX) in the intervention group and –2.0 (SD=XX) in the placebo group (p=0.23).

Discussion This study met the primary outcome demonstrating that it is feasible for randomised participants to complete the study medication and procedures. The high placebo response rate and wide confidence interval informs us that a large sample size would be required to power a definitive phase III study. This data suggests that while the study design is feasible once participants are recruited, the slow recruitment rate would necessitate a large number of sites and resources to determine the benefit of continuous subcutaneous infusion of lidocaine using this methodology. These results inform future clinical trials of lidocaine and other analgesics which may need to consider how to optimise recruitment through study design and processes.

This feasibility study is not powered for efficacy, limiting the significance of findings for pain reduction. The placebo response rate in this study was very high compared to other pain studies which commonly find a reduction of about 20% in pain intensity.

The evidence base in palliative care has grown rapidly in the past 30 years transforming the way we practice medicine. This study provides important insights into design and feasibility of clinical trials of lidocaine for people with neuropathic cancer pain.