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

NCT ID: NCT03428230

Last Updated: 2021-06-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-06
• Study Completion Date: 2019-10-22

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%.

Detailed Description

Eligible patients undergoing elective short-duration knee procedures up to 40 min duration will be randomised into 4 treatment groups (15 patients per group) to receive either one of the 3 single doses of Paracetamol 3% (D1: 30 mg, D2: 60 mg, D3: 90 mg) or the placebo solution (P: 0.9% saline solution) by intrathecal injection (IT), according to the randomised, parallel-group design.

Immediately after IT paracetamol or placebo administration, all patients will receive a single IT dose of Chloroprocaine HCl 1% (Non-investigational medicinal product, NIMP) according to the Summary of Product Characteristics indications. The time interval between paracetamol IT and chloroprocaine IT injections should not exceed 2 min.

The study will include a screening phase (Visit 1, Day -21/-1), a treatment phase (IMP IT administration, anaesthesia and surgical procedure: Visit 2, Day 1) and a follow-up phase including an observation period (Visit 3), a final visit and two follow-ups (24 h post-dose and day 7±1).

Conditions

Pain, Postoperative

Study Design

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

Study Groups

30 mg Paracetamol 3% (1 mL)

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

Group Type: EXPERIMENTAL

30 mg Paracetamol 3% (1 mL)

Intervention Type: 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.

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

Intervention Type: 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.

60 mg Paracetamol 3% (2 mL)

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

Group Type: EXPERIMENTAL

60 mg Paracetamol 3% (2 mL)

Intervention Type: 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.

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

Intervention Type: 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.

90 mg Paracetamol 3% (3 mL)

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

Group Type: EXPERIMENTAL

90 mg Paracetamol 3% (3 mL)

Intervention Type: 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.

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

Intervention Type: 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.

Placebo, 0.9% saline solution

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

Group Type: PLACEBO_COMPARATOR

Placebo, 0.9% saline solution

Intervention Type: 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.

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

Intervention Type: 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.

Interventions

30 mg Paracetamol 3% (1 mL)

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.

Intervention Type: DRUG

60 mg Paracetamol 3% (2 mL)

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.

Intervention Type: DRUG

90 mg Paracetamol 3% (3 mL)

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.

Intervention Type: DRUG

Placebo, 0.9% saline solution

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.

Intervention Type: DRUG

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

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 Type: DRUG

Other Intervention Names

physiological solution; Ampres 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)]

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

Sponsors

Cross Research 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

Department of Anaesthesiology, Clinica Ars Medica

Gravesano, , Switzerland

Countries

Switzerland

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

CRO-17-133

Identifier Type: OTHER

Identifier Source: secondary_id

PAR.3-01-2017

Identifier Type: -

Identifier Source: org_study_id