Dose-finding Study of Intrathecal Paracetamol Administered Immediately Before Spinal Anaesthesia

NCT ID: NCT02654860

Last Updated: 2021-10-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-30
• Study Completion Date: 2019-02-28

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.

Conditions

Phase 1: Pain Management; Phase 2: Pain Management

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: DOUBLE

Study Groups

60 mg Paracetamol 3% (2 mL)

60 mg Paracetamol 3%. Solution for injection, single administration by Intrathecal route.

Group Type: EXPERIMENTAL

Paracetamol 3%

Intervention Type: DRUG

Investigate the efficacy and safety of a single intrathecal injection of paracetamol,for post-operative analgesia of hip replacement surgery

Hyperbaric Bupivacaine HCl 0.5%

Intervention Type: DRUG

NIMP, spinal anaesthetic before the surgical procedure

90 mg Paracetamol 3% (3 mL)

90 mg Paracetamol 3%. Solution for injection, single administration by Intrathecal route.

Group Type: EXPERIMENTAL

Paracetamol 3%

Intervention Type: DRUG

Investigate the efficacy and safety of a single intrathecal injection of paracetamol,for post-operative analgesia of hip replacement surgery

Hyperbaric Bupivacaine HCl 0.5%

Intervention Type: DRUG

NIMP, spinal anaesthetic before the surgical procedure

120 mg Paracetamol 3% (4mL)

120 mg Paracetamol 3%. Solution for injection, single administration by Intrathecal route.

Group Type: EXPERIMENTAL

Paracetamol 3%

Intervention Type: DRUG

Investigate the efficacy and safety of a single intrathecal injection of paracetamol,for post-operative analgesia of hip replacement surgery

Hyperbaric Bupivacaine HCl 0.5%

Intervention Type: DRUG

NIMP, spinal anaesthetic before the surgical procedure

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.

Group Type: PLACEBO_COMPARATOR

Placebo injection containing Saline solution 0.9%

Intervention Type: DRUG

Injection containing sterile solution of Saline Solution 0.9 %. 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.

Hyperbaric Bupivacaine HCl 0.5%

Intervention Type: DRUG

NIMP, spinal anaesthetic before the surgical procedure

Interventions

Paracetamol 3%

Investigate the efficacy and safety of a single intrathecal injection of paracetamol,for post-operative analgesia of hip replacement surgery

Intervention Type: DRUG

Placebo injection containing Saline solution 0.9%

Injection containing sterile solution of Saline Solution 0.9 %. 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 Type: DRUG

Hyperbaric Bupivacaine HCl 0.5%

NIMP, spinal anaesthetic before the surgical procedure

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Informed consent: signed written informed consent before inclusion in the study
• Sex, age and surgery: male/female 18-80 years (inclusive) old patients, scheduled for hip replacement surgery, with anticipated need for post-operative narcotic analgesia, adequate i.v. access and anticipated hospital stay > 48 hours.
• Body Mass Index (BMI): 18 - 34 kg/m2 inclusive
• ASA physical status: I-III
• Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the entire study

Exclusion Criteria

• Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study. Contraindications to spinal anaesthesia. History of neuromuscular diseases to the lower extremities
• ASA physical status: IV-V
• Further anaesthesia: patients expected to require further anaesthesia
• Pain assessment: anticipated to be unable to make a reliable self-report of pain intensity
• Allergy: ascertained or presumptive hypersensitivity to the active principles (paracetamol and/or amide type anaesthetics) and/or formulations' ingredients or related drugs, opioids, non-steroidal anti-inflammatory drugs; history of anaphylaxis to drugs or allergic reactions in general, which the investigator considers could affect the outcome of the study
• Diseases: significant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine or neurological diseases that may interfere with the aim of the study; ascertained psychiatric and neurological diseases, sepsis, blood coagulation disorders, severe cardiopulmonary disease, thyroid disease, diabetes, other neuropathies, history or evidence of asthma or heart failure. History of severe head trauma that required hospitalisation, intracranial surgery or stroke within the previous 30 days, or any history of intracerebral arteriovenous malformation, cerebral aneurism or CNS mass lesion.
• Liver function: Impaired liver function (transaminases > twice upper limit)
• Renal function: Renal dysfunction (creatinine > 2.0 mg/dL)
• Investigative drug studies: participation in the evaluation of any investigational product for 3 months before this study, calculated from the first day of the month following the last visit of the previous study
• Drug, alcohol: history of drug or alcohol abuse. Pre-existing dependence on narcotics or known tolerance to opioids
• Pregnancy and lactation: positive pregnancy test at screening (if applicable), pregnant or lactating women [The pregnancy test will be performed to all fertile women and to all women up to 55 years old, if not in proven menopause (available laboratory test confirming menopause or surgically sterilised)]
• Chronic pain syndromes: patients with chronic pain syndromes (taking opioids, anticonvulsant agents or chronic analgesic therapy).
• Medications: medication known to interfere with the extent of spinal blocks for 2 weeks before the start of the study. Paracetamol formulations, other than the investigational product, for 1 week before the start of the study and during the study. Hormonal contraceptives for females are allowed.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cross S.A.

INDUSTRY

Sponsor Role: collaborator

Sintetica SA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Claudio Camponovo, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Anaesthesiology,Clinica Ars Medica,Via Cantonale, CH-6929 Gravesano, Switzerland

Locations

Claudio Camponovo

Gravesano, Lugano, Switzerland

Countries

Switzerland

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

PAR.3/02-2015

Identifier Type: -

Identifier Source: org_study_id