HBOT Conversations:

This is a prospective, single centre, two-part, three doses study. Part 1 is a Phase I, three
cohorts, dose-ascending, open-label, safety study. Part 2 is a Phase II, randomised,
parallel-group, double-blind, placebo-controlled, exploratory efficacy and safety study The
objective of the study is to investigate the efficacy and safety of a single intrathecal
injection of paracetamol, administered at 3 doses to 3 active treatment groups, as compared
to placebo solution, for post-operative analgesia of hip replacement surgery performed under
spinal anaesthesia. Patients scheduled for hip replacement surgery will be randomised into 4
treatment groups (15 patients per group) to receive either one of the 3 single doses of
paracetamol 3% (D1: 60 mg, D2: 90 mg, D3: 120 mg) or placebo solution (P: saline solution) by
intrathecal (IT) injection. Immediately after paracetamol or placebo IT administration, all
patients will receive a single IT dose of Hyperbaric Bupivacaine HCl 0.5% (12.5 mg for ≤ 160
cm-tall patients and 15 mg for > 160 cm-tall patients). The time interval between paracetamol
IT and bupivacaine IT administrations should not exceed 2 min.

The study will include a screening phase (Visit 1, Days -21/1), a treatment phase
(paracetamol IT administration, anaesthesia and surgical procedure: Visit 2, Day 1) and a
follow-up phase including an observation period (Visit 3, from Day 1 after surgery until
discharge, a final visit (at discharge) and a follow-up (day 6±1). Pain at rest will be
assessed at screening and on visit 2 at baseline (0 h), 1, 2, 3, 6, 9, 12, 15, 18, 21, 24,
27, 30, 33, 36, 39, 42, 45 and 48 h after anaesthetic IT injection and at discharge, using a
0-100 mm VAS.