IV acetaminophen (IV-APAP) is available in Europe (Bristol-Myers Squibb) for the treatment of acute pain and fever and is currently under clinical investigation in the US (Cadence Pharmaceuticals).

MATERIALS AND METHODS:

This multi-center, double-blind, randomized, placebo-controlled study was conducted in patients undergoing elective total hip arthroplasty. Patients' PCA was discontinued the morning after surgery and patients were randomized when their pain intensity (PI) was moderate or severe (100-mm VAS >45) to either IV-APAP 1 g/100 mL or placebo (Pbo). Study drug was infused IV over 15-minutes at 0, 4, 10 and 16 h. Rescue medication was freely available. Primary efficacy outcomes included PI difference from baseline (PID) at 1, 2, 3 and 4 h post-dose and subject global evaluation at bedtime on Day 1. Safety evaluations included adverse event (AE) reporting, exams, ECGs, and labs (e.g., LFTs). The study was stopped due to particulates in Pbo vials (planned enrollment: 230).

RESULTS:

Patients randomized: IV-APAP (n=30) or Pbo (n=31) with 52 completers (IV-APAP: n=27; Pbo: n=25). IV-APAP demonstrated statistically significant improvement compared to Pbo in PIDs at all timepoints from 0.25 to 3 h post-dose (p°Ü .03), in time to first rescue [>4 h vs. 1.25h (p= .001)], and in rescue morphine (equivalents) consumption [1.9 mg vs. 5.1 mg (p= .006)]. Global evaluation at bedtime was rated good or excellent by 24 (85.7%) patients treated with IV-APAP vs. 11 (39.3%) with Pbo (p= .0003). IV-APAP was well tolerated. One patient in the IV-APAP group exceeded the 4 g/day maximum due to concomitant oral acetaminophen, but had no AEs. There were no clinically meaningful differences in AEs, labs, vital signs, exams or ECGs.

CONCLUSIONS:

IV acetaminophen was more efficacious than placebo in treating acute pain after hip arthroplasty resulting in significantly longer time to rescue and decrease in overall opioid consumption.