Intrathecal Paracetamol Before Spinal Anaesthesia With Chloroprocaine HCl 1% for Short Knee Procedures

NCT03428230 | Completed Phase 2 Results

• 2 other identifiers: PAR.3-01-2017CRO-17-133
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II, single centre, randomised, parallel-group, double-blind, three doses, placebo-controlled, exploratory efficacy and safety study. The objective of this study is to investigate the efficacy and safety of a single intrathecal injection of Paracetamol 3% (30 mg/mL) administered at 3 doses to 3 active treatment groups, as compared to placebo, for post-operative analgesia in knee procedures up to 40 min duration performed under spinal anaesthesia with Chloroprocaine HCl 1%.

Conditions

Pain, Postoperative

Outcome Measures

Primary Outcomes (1)

• Pain Intensity at Rest Evaluated Using a 0-100 mm VAS

  The study primary efficacy measures will be the VAS scores at each predefined time-point after the anaesthetic intrathecal injection until eligibility for home discharge ( VAS scale is 0-100 mm, where 0 is no pain and 100 is maximum pain)

  Pain intensity at rest evaluated using a 0-100 mm VAS at baseline (within 30 min before NIMP IT injection, 0 h), 1, 1.25, 1.5, 1.75, 2 h after NIMP IT injection, then every 30 min after NIMP IT injection until eligibility for home discharge.

Secondary Outcomes (21)

• Pain at Rest AUCt1-t2

  Up to 4 hours after injection

• Pain at Rest AUClast

  Up to 24 hours after injection

• Time to First Postoperative Analgesia (Level 1 or 2)

  Up to 24 hours after surgery

• Partecipants to Received Level 1 Analgesia

  from surgery day to 24 hours after surgery

• Partecipants Received Level 2 Analgesia

  from surgery day to 24 hours after surgery

Other Outcomes (1)

• Number of Participants With Neurological Complications Including TNS

  From anaesthetic intrathecal injection up to day 7±1 (i.e. 6±1 days after analgesic/anaesthetic IT injection and surgery)

Study Arms (4)

30 mg Paracetamol 3% (1 mL)

EXPERIMENTAL

30 mg Paracetamol 3% (1 mL), solution for injection, single dose by intrathecal injection (IT)

Drug: 30 mg Paracetamol 3% (1 mL); Drug: NIMP: Chloroprocaine HCl 1% (10 mg/mL), solution for injection

60 mg Paracetamol 3% (2 mL)

EXPERIMENTAL

60 mg Paracetamol 3% (2 mL), solution for injection, single dose by intrathecal injection (IT)

Drug: 60 mg Paracetamol 3% (2 mL); Drug: NIMP: Chloroprocaine HCl 1% (10 mg/mL), solution for injection

90 mg Paracetamol 3% (3 mL)

EXPERIMENTAL

90 mg Paracetamol 3% (3 mL), solution for injection, single dose by intrathecal injection (IT)

Drug: 90 mg Paracetamol 3% (3 mL); Drug: NIMP: Chloroprocaine HCl 1% (10 mg/mL), solution for injection

Placebo, 0.9% saline solution

PLACEBO COMPARATOR

Placebo, 0.9% saline solution (1 mL, 2 mL or 3 mL), solution for injection, single dose by intrathecal injection (IT)

Drug: Placebo, 0.9% saline solution; Drug: NIMP: Chloroprocaine HCl 1% (10 mg/mL), solution for injection

Interventions

30 mg Paracetamol 3% (1 mL) DRUG

Single administration by intrathecal injection just before spinal anaesthesia. The injection will be performed according to the hospital procedures. For the intrathecal injection of Paracetamol followed by the intrathecal injection of the anaesthetic, two needles will be used: one introducer needle, which will serve to introduce the second needle through the skin, plus one intrathecal Pencil point needle (27-G or 25-Gauge or Reganesth or Nizell needle) to which the first syringe containing Paracetamol will be attached first, followed by the second syringe with the anaesthetic. In this way only one intrathecal puncture will be performed. Lumbar puncture will be done according to the standard hospital procedures.

30 mg Paracetamol 3% (1 mL)

60 mg Paracetamol 3% (2 mL) DRUG

Single administration by intrathecal injection just before spinal anaesthesia. The injections will be performed according to the hospital procedures. For the intrathecal injection of Paracetamol followed by the intrathecal injection of the anaesthetic, two needles will be used: one introducer needle, which will serve to introduce the second needle through the skin, plus one intrathecal Pencil point needle (27-G or 25-Gauge or Reganesth or Nizell needle) to which the first syringe containing Paracetamol will be attached first, followed by the second syringe with the anaesthetic. In this way only one intrathecal puncture will be performed. Lumbar puncture will be done according to the standard hospital procedures.

60 mg Paracetamol 3% (2 mL)

90 mg Paracetamol 3% (3 mL) DRUG

Single administration by intrathecal injection just before spinal anaesthesia. The injections will be performed according to the hospital procedures. For the intrathecal injection of Paracetamol followed by the intrathecal injection of the anaesthetic, two needles will be used: one introducer needle, which will serve to introduce the second needle through the skin, plus one intrathecal Pencil point needle (27-G or 25-Gauge or Reganesth or Nizell needle) to which the first syringe containing Paracetamol will be attached first, followed by the second syringe with the anaesthetic. In this way only one intrathecal puncture will be performed. Lumbar puncture will be done according to the standard hospital procedures.

90 mg Paracetamol 3% (3 mL)

Placebo, 0.9% saline solution DRUG

Single administration by intrathecal injection just before spinal anaesthesia. The injections will be performed according to the hospital procedures. For the intrathecal injection of Placebo followed by the intrathecal injection of the anaesthetic, two needles will be used: one introducer needle, which will serve to introduce the second needle through the skin, plus one intrathecal Pencil point needle (27-G or 25-Gauge or Reganesth or Nizell needle) to which the first syringe containing Placebo will be attached first, followed by the second syringe with the anaesthetic. In this way only one intrathecal puncture will be performed. Lumbar puncture will be done according to the standard hospital procedures.

Also known as: physiological solution

Placebo, 0.9% saline solution

NIMP: Chloroprocaine HCl 1% (10 mg/mL), solution for injection DRUG

Immediately after intrathecal administration of the Paracetamol dose or Placebo, all patients will receive a single intrathecal dose of Chloroprocaine HCl 1% according to the Summary of Product Characteristics indications. Time interval between the 2 administrations should not exceed 2 min.

Also known as: Ampres 1%

30 mg Paracetamol 3% (1 mL); 60 mg Paracetamol 3% (2 mL); 90 mg Paracetamol 3% (3 mL); Placebo, 0.9% saline solution

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 patients, 18-80 years old (inclusive), scheduled for short duration (up to 40 min) knee procedures
• Body Mass Index (BMI): 18 - 32 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
• Allergy: ascertained or presumptive hypersensitivity to the active principles (paracetamol and/or ester type anaesthetics) and/or formulations' ingredients or related drugs, non-steroidal anti-inflammatory drugs and/or opioid derivatives; history of anaphylaxis to drugs or allergic reactions in general, which the investigator considers could affect the outcome of the study
• Chronic pain syndromes: patients with chronic pain syndromes taking opioids, anticonvulsant agents or chronic analgesic therapy
• Pain assessment: patients anticipated to be unable to make a reliable self-report of pain intensity
• 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 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
• 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 2 weeks before the start of the study and during the study. Hormonal contraceptives for females are allowed. Anti-hypotensive, anti-bradycardia (e.g. ephedrine, atropine, Ringer's solution), anti-haemetic and anti-nausea medications will be allowed
• Investigative drug studies: participation in the evaluation of any investigational product for 3 months before this study. The 3-month interval is calculated as the time between the first calendar day of the month that follows the last visit of the previous study and the first day of the present study
• Drug, alcohol: history of drug or alcohol abuse according to the Investigator's opinion
• Pregnancy and lactation: positive pregnancy test at screening (if applicable), pregnant or lactating women \[The pregnancy test will be performed to all fertile women and to all women up to 55 years old, if not in proven menopause (available laboratory test confirming menopause or surgically sterilised)\]

Sponsors & Collaborators

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

Study Sites (1)

Department of Anaesthesiology, Clinica Ars Medica

Gravesano, 6929, Switzerland

Location

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Acetaminophen; Saline Solution; Solutions; Injections

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Crystalloid Solutions; Isotonic Solutions; Pharmaceutical Preparations; Drug Administration Routes; Drug Therapy; Therapeutics

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 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study will be double-blind. Neither the Investigator/co-investigators/study nurses involved in the clinical study procedures, nor will the patients be aware of the administered treatment. At the site, syringes for injection will then be prepared by a person not involved in any other study-related activities where a bias is possible.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Eligible patients will be randomised into four treatment groups (15 patients/group) to receive either one of the three single doses of Paracetamol 3% (30 mg, 60 mg, 90 mg) or placebo solution (1 mL, 2 mL, 3 mL) according to the randomised, parallel-group design.

Study Record Dates

• First Submitted: January 23, 2018
• First Posted: February 9, 2018
• Study Start: August 6, 2018
• Primary Completion: October 22, 2019
• Study Completion: October 22, 2019
• Last Updated: June 24, 2021
• Results First Posted: June 24, 2021

Record last verified: 2021-06

Locations

CH (1)