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

NCT02654860 | Completed Phase 1 Results DMC

• 1 other identifier: PAR.3/02-2015
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Phase 1: Pain Management; Phase 2: Pain Management

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (12)

• 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: 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: Time to Readiness for Surgery

  Intraoperative

Study Arms (4)

60 mg Paracetamol 3% (2 mL)

EXPERIMENTAL

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

Drug: Paracetamol 3%; Drug: Hyperbaric Bupivacaine HCl 0.5%

90 mg Paracetamol 3% (3 mL)

EXPERIMENTAL

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

Drug: Paracetamol 3%; Drug: Hyperbaric Bupivacaine HCl 0.5%

120 mg Paracetamol 3% (4mL)

EXPERIMENTAL

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

Drug: Paracetamol 3%; Drug: Hyperbaric Bupivacaine HCl 0.5%

Phase II Only: Saline solution 0.9%

PLACEBO COMPARATOR

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.

Drug: Placebo injection containing Saline solution 0.9%; Drug: Hyperbaric Bupivacaine HCl 0.5%

Interventions

Paracetamol 3% DRUG

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

120 mg Paracetamol 3% (4mL); 60 mg Paracetamol 3% (2 mL); 90 mg Paracetamol 3% (3 mL)

Placebo injection containing Saline solution 0.9% 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.

Phase II Only: Saline solution 0.9%

Hyperbaric Bupivacaine HCl 0.5% DRUG

NIMP, spinal anaesthetic before the surgical procedure

120 mg Paracetamol 3% (4mL); 60 mg Paracetamol 3% (2 mL); 90 mg Paracetamol 3% (3 mL); Phase II Only: Saline solution 0.9%

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sintetica SA: lead
• Cross S.A.: collaborator

Study Sites (1)

Claudio Camponovo

Gravesano, Lugano, CH-6929, Switzerland

Location

MeSH Terms

Interventions

3-(cystein-S-yl)paracetamol

Results Point of Contact

• Title: Dr.Elisabetta Donati, Corporate Director Scientific Affairs
• Organization: Sintetica SA

edonati@sintetica.com

+41.91.640.42.50

Study Officials

• Claudio Camponovo, MD

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Phase II only
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 4 arms for Phase II only

Study Record Dates

• First Submitted: December 23, 2015
• First Posted: January 13, 2016
• Study Start: November 1, 2016
• Primary Completion: February 1, 2019
• Study Completion: February 1, 2019
• Last Updated: October 27, 2021
• Results First Posted: June 1, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)