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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02654860
Other study ID # PAR.3/02-2015
Secondary ID
Status Completed
Phase Phase 1/Phase 2
First received
Last updated
Start date November 2016
Est. completion date February 2019

Study information

Verified date July 2021
Source Sintetica SA
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Two-part study of intrathecal paracetamol administered immediately before spinal anaesthesia in patients scheduled for hip replacement surgery


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.


Recruitment information / eligibility

Status Completed
Enrollment 69
Est. completion date February 2019
Est. primary completion date February 2019
Accepts healthy volunteers No
Gender All
Age group 18 Years to 80 Years
Eligibility Inclusion Criteria Phase 1 and Phase 2: - 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 - Inclusion criteria - Phase 1 only : Age: 18-70 (inclusive) old patients - Inclusion criteria - Phase 2 only : Age: 18-80 (inclusive) old patients Hospital stay: Patients with anticipated hospital stay > 48 hours Exclusion Criteria Phase 1 and Phase 2: - 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. - Phase 2 only - Exclusion criteria Pain assessment: anticipated to be unable to make a reliable self-report of pain intensity

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Paracetamol 3%
Investigate the efficacy and safety of a single intrathecal injection of paracetamol,for post-operative analgesia of hip replacement surgery
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.
Hyperbaric Bupivacaine HCl 0.5%
NIMP, spinal anaesthetic before the surgical procedure

Locations

Country Name City State
Switzerland Claudio Camponovo Gravesano Lugano

Sponsors (2)

Lead Sponsor Collaborator
Sintetica SA Cross S.A.

Country where clinical trial is conducted

Switzerland, 

Outcome

Type Measure Description Time frame Safety issue
Primary Phase 1: Number of Participants With Adverse Events Related, Not Related and Serious Events Related to Paracetamol 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 In the first 24 hours, in the first 48 hours and at day 7±1
Primary Phase 2: Pain Intensity 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) baseline (0 h), 1, 6, 9, 12, 15, 24, and 48 h after anaesthetic IT injection and at discharge
Secondary Phase 2: Morphine Phase 2: Total morphine use At 24 and 48 h after anaesthetic IT injection and entire study period, up to 7 days
Secondary Phase 2: Time to First Morphine Use Phase 2: Time to first morphine use (minutes) Postoperative, up to 48 hours after end of surgery
Secondary Phase 2: Number of Participants With Need for Supplemental Analgesia Phase 2: Need for supplementary analgesia, other than the planned morphine PCA Postoperative, up to 48 hours after end of surgery
Secondary Phase 2: Morphine-related Adverse Events Percentage of subjects experiencing during the study the morphine-related adverse events pre-specified in the protocol up to 24 hours after surgery, up to 48 hours
Secondary Phase 2: Time to Readiness for Surgery Time period from completion of spinal injection (time 0 h) to achievement of sensory and motor block adequate for surgery. Intraoperative
Secondary Phase 2:Maximum Level of Sensory Block Sensorial block will be verified by bilateral Pinprick test using a 20-G hypodermic needle and will be recorded. Pinprick sensation will be scored as being present (score 1) or absent (score 0). Onset of sensory block is defined as an absent touch sensation (score 0) Intraoperative
Secondary Phase 2: Time to Sensory Block Time to maximum level of sensory block Intraoperative
Secondary Phase 2: Time to Regression of Spinal Block Time period from spinal injection (time 0 h) to the time when the Bromage score returns to 0 and sensitive perception returns to S1. Bromage scale:
I - Free movement of legs and feet II - Just able to flex knees with free movement of feet III - Unable to flex knees, but with free movement of feet IV - Unable to move legs or feet
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
Secondary Phase 2: Vital Signs Systolic and Diastolic Blood Pressure (mmHg) at screening, at baseline (before the spinal injection) and at end of the study (Day 6).
Secondary Phase2: Concomitant Medications record the concomitant medications intaked during the study at screening, at baseline until the end of the study (Day 6)
Secondary Phase 2: SpO2 Oxygen saturation is the fraction of oxygen-saturated hemoglobin relative to total hemoglobin (unsaturated + saturated) in the blood. at screening, at baseline (before the spinal injection) and at the end of the study (day 6)
Secondary Phase 2: ECG Electrocardiography is the process of producing an electrocardiogram (ECG), it is a graph of voltage versus time of the electrical activity of the heart using electrodes placed on the skin. screening, baseline and end of study (Day 6±1)