Intrathecal Paracetamol Before Spinal Anaesthesia With Chloroprocaine HCl 1% for Short Knee Procedures
Condition: Pain, Postoperative
MeSH terms: Pain, Postoperative
Intervention: 30 mg Paracetamol 3% (1 mL); 60 mg Paracetamol 3% (2 mL); 90 mg Paracetamol 3% (3 mL); Placebo, 0.9% saline solution; NIMP: Chloroprocaine HCl 1% (10 mg/mL), solution for injection
Intervention description: 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.; 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.; 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.; 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.; 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.
Intervention MeSH terms: Acetaminophen; Chloroprocaine; Pharmaceutical Solutions
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 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.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking description: 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.
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

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%.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Informed consent: signed written informed consent before inclusion in the study

          2. Sex, age and surgery: male/female patients, 18-80 years old (inclusive), scheduled for
             short duration (up to 40 min) knee procedures

          3. Body Mass Index (BMI): 18 - 32 kg/m2 inclusive

          4. ASA physical status: I-III

          5. 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:

          1. 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

          2. ASA physical status: IV-V

          3. Further anaesthesia: patients expected to require further anaesthesia

          4. 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

          5. Chronic pain syndromes: patients with chronic pain syndromes taking opioids,
             anticonvulsant agents or chronic analgesic therapy

          6. Pain assessment: patients anticipated to be unable to make a reliable self-report of
             pain intensity

          7. 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

          8. 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

          9. 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

         10. Drug, alcohol: history of drug or alcohol abuse according to the Investigator's
             opinion

         11. 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)]