Two-part Study of Intrathecal Paracetamol Administered Immediately Before Spinal Anaesthesia in Patients Scheduled for Hip Replacement Surgery
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Sintetica SA
- Enrollment
- 69
- Locations
- 1
- Primary Endpoint
- Phase 2: Pain Intensity
Study Overview
Brief Summary
Two-part study of intrathecal paracetamol administered immediately before spinal anaesthesia in patients scheduled for hip replacement surgery
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Supportive Care
- Masking
- Double (Participant, Investigator)
Masking Description
Phase II only
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
60 mg Paracetamol 3% (2 mL)
60 mg Paracetamol 3%. Solution for injection, single administration by Intrathecal route.
Intervention: Paracetamol 3% (Drug)
60 mg Paracetamol 3% (2 mL)
60 mg Paracetamol 3%. Solution for injection, single administration by Intrathecal route.
Intervention: Hyperbaric Bupivacaine HCl 0.5% (Drug)
90 mg Paracetamol 3% (3 mL)
90 mg Paracetamol 3%. Solution for injection, single administration by Intrathecal route.
Intervention: Paracetamol 3% (Drug)
90 mg Paracetamol 3% (3 mL)
90 mg Paracetamol 3%. Solution for injection, single administration by Intrathecal route.
Intervention: Hyperbaric Bupivacaine HCl 0.5% (Drug)
120 mg Paracetamol 3% (4mL)
120 mg Paracetamol 3%. Solution for injection, single administration by Intrathecal route.
Intervention: Paracetamol 3% (Drug)
120 mg Paracetamol 3% (4mL)
120 mg Paracetamol 3%. Solution for injection, single administration by Intrathecal route.
Intervention: Hyperbaric Bupivacaine HCl 0.5% (Drug)
Phase II Only: Saline solution 0.9%
Placebo, 0.9%. Solution for injection , single administration by route Intrathecal (2 mL, 3 mL and 4 mL) Study part 2 will be placebo-controlled. Each patient will be allocated to a treatment arm (one of the three paracetamol doses or placebo) according to a computer-generated randomisation list.
Intervention: Placebo injection containing Saline solution 0.9% (Drug)
Phase II Only: Saline solution 0.9%
Placebo, 0.9%. Solution for injection , single administration by route Intrathecal (2 mL, 3 mL and 4 mL) Study part 2 will be placebo-controlled. Each patient will be allocated to a treatment arm (one of the three paracetamol doses or placebo) according to a computer-generated randomisation list.
Intervention: Hyperbaric Bupivacaine HCl 0.5% (Drug)
Outcomes
Primary Outcomes
Phase 2: Pain Intensity
Time Frame: baseline (0 h), 1, 6, 9, 12, 15, 24, and 48 h after anaesthetic IT injection and at discharge
Phase 2: Pain intensity at rest evaluated as VAS scores ( 0-100 mm visual analogue scale : 0 is the absence pain and 100 is the maximum pain sensation)
Phase 1: Number of Participants With Adverse Events Related, Not Related and Serious Events Related to Paracetamol
Time Frame: In the first 24 hours, in the first 48 hours and at day 7±1
Phase 1: Number of participants with treatment evaluation and confirmation of the safety of the three doses of paracetamol 3% solution administered in the total number of patients enrolled
Secondary Outcomes
- Phase 2: Number of Participants With Need for Supplemental Analgesia(Postoperative, up to 48 hours after end of surgery)
- Phase 2: Morphine-related Adverse Events(up to 24 hours after surgery, up to 48 hours)
- Phase 2:Maximum Level of Sensory Block(Intraoperative)
- Phase 2: ECG(screening, baseline and end of study (Day 6±1))
- Phase 2: Morphine(At 24 and 48 h after anaesthetic IT injection and entire study period, up to 7 days)
- Phase 2: Time to First Morphine Use(Postoperative, up to 48 hours after end of surgery)
- Phase 2: Time to Sensory Block(Intraoperative)
- Phase 2: SpO2(at screening, at baseline (before the spinal injection) and at the end of the study (day 6))
- Phase 2: Time to Readiness for Surgery(Intraoperative)
- Phase 2: Time to Regression of Spinal Block(from readiness for surgery,then every 10 min until the maximum level is reached (two consecutive observations with the same level of sensory block) and then every 30 min until regression of spinal block)
- Phase 2: Vital Signs(at screening, at baseline (before the spinal injection) and at end of the study (Day 6).)
- Phase2: Concomitant Medications(at screening, at baseline until the end of the study (Day 6))