Pain, Postoperative
Conditions
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).
Interventions
DRUG30 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.
DRUG60 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.
DRUG90 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.
DRUGPlacebo, 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.
DRUGNIMP: 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.
Sponsors
Cross Research S.A.
Sintetica SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, 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.
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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 \[The pregnancy test will be performed to all fertile women and to all women up to 55 years old, if not in proven menopause (available laboratory test confirming menopause or surgically sterilised)\]
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 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. | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain at Rest AUCt1-t2 | Up to 4 hours after injection | AUC t1-t2 is defined as the area under the pain intensity curve at the specified time-intervals |
| Pain at Rest AUClast | Up to 24 hours after injection | AUClast is defined as the area under the pain intensity curve from 0 h up to the last assessment time |
| Time to First Postoperative Analgesia (Level 1 or 2) | Up to 24 hours after surgery | Postoperatively, patients will be administered an analgesic as needed. Post-operative analgesia could include Ketorolac i.v. \[Toradol\] 30 mg (level 1 analgesia) and/or Tramadol i.v. 1 mg/kg (level 2 analgesia). The administered analgesic (level 1 or 2), analgesic dose and intake frequency will be decided according to the reported surgery-related pain intensity. Post-operatively, patients were administered an analgesic, as needed. Post-operative analgesia could include Ketorolac i.v. \[Toradol\] 30 mg (level 1 analgesia) and/or Tramadol i.v. 1 mg/kg (level 2 analgesia). |
| Partecipants to Received Level 1 Analgesia | from surgery day to 24 hours after surgery | Partecipants to received Ketorolac i.v. \[Toradol\] 30 mg administration (level 1 analgesia) |
| Partecipants Received Level 2 Analgesia | from surgery day to 24 hours after surgery | Partecipants received Tramadol i.v. 1 mg/kg administration (level 2 analgesia) |
| Total Number of Partecipants Receiving Analgesic 1 | From surgery day to 24 hours after surgery | Total number of partecipants receiving Ketorolac i.v. \[Toradol\] 30 mg |
| Total Number of Partecipants Receiving Analgesic 2 | from surgery day to 24 hours after surgery | Total Number of Partecipants Receiving Tramadol i.v. 1 mg/kg |
| Percentage of Patients Requiring Analgesia in the First 2 h After Surgery End | Form surgery day to 2 hours after surgery end | Percentage of patients requiring analgesia (level 1 or level 2) in the first 2 h after surgery end |
| Percentage of Patients Requiring Analgesia in the First 4 h After Surgery End | from surgery day to 4 hours after surgery end | Percentage of patients requiring analgesia (level 1 or level 2) in the first 4 h after surgery end |
| Percentage of Patients Requiring Analgesia From Surgery End Until Eligibility for Discharge | from surgery day to 24 hours after surgery | Percentage of patients requiring analgesia (level 1 or level 2) from surgery end until eligibility for home discharge |
| Percentage of Patients Requiring Level 2 Analgesia From Surgery End Until Eligibility for Discharge | from surgery day to 24 hours after surgery | Percentage of Patients Requiring Level 2 Analgesia From Surgery End Until Eligibility for Home Discharge |
| Percentage of Patients Requiring Supplementary Analgesia, Other Than the Planned Level 1 or 2 Analgesia | from surgery day to 24 hours after surgery | Percentage of patients requiring supplementary analgesia, other than the planned level 1 or 2 analgesia |
| Percentage of Patients Requiring Rescue Anaesthesia | from surgery day to 1 hour after injection | Percentage of patients requiring rescue anaesthesia |
| Time to Onset of Spinal Block (i.e. Time to Readiness for Surgery) | Up to 20 minutes after injection | Spinal block/Readiness for surgery is defined as the presence of an adequate motor block (Bromage's score ≥ 2) and loss of Pinprick sensation, according to the Investigator's opinion. Time to readiness for surgery is defined as the time from the spinal injection (time 0 h) to achievement of readiness for surgery. |
| Maximum Sensory Block | Intraoperative | Maximum level of sensory block |
| Time to Sensory Block | Intraoperative | Time to maximum level of sensory block (bilateral Pinprick test using a 20-G hypodermic needle) |
| Time to Regression of Spinal Block | Up to 4 hours after injection | Time period from spinal injection to the complete regression of sensory block to S1. |
| Time to Ambulation | Up to 24 hours after injection | Time to unassisted ambulation |
| Time to First Urine | Up to 24 hours after injection | Time to first spontaneous urine voiding |
| Time to Eligibility for Discharge | Up to 24 hours after injection | Time to eligibility for home discharge |
| Percentage of Patients Requiring Level 1 Analgesia From Surgery End Until Eligibility for Discharge | from surgery day to 24 hours after surgery | Percentage of patients requiring level 1 analgesia from surgery end until eligibility for home discharge |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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) | Number of Participants with Neurological Complications Including TNS at 24 h post-dose and at day 7±1 |
Countries
Switzerland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 30 mg Paracetamol 3% (1 mL) 30 mg Paracetamol 3% (1 mL), solution for injection, single dose by intrathecal injection (IT)
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.
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. | 15 |
| 60 mg Paracetamol 3% (2 mL) 60 mg Paracetamol 3% (2 mL), solution for injection, single dose by intrathecal injection (IT)
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.
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. | 15 |
| 90 mg Paracetamol 3% (3 mL) 90 mg Paracetamol 3% (3 mL), solution for injection, single dose by intrathecal injection (IT)
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.
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. | 15 |
| 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)
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.
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. | 15 |
| Total | 60 |
Baseline characteristics
| Characteristic | 30 mg Paracetamol 3% (1 mL) | Total | Placebo, 0.9% Saline Solution | 90 mg Paracetamol 3% (3 mL) | 60 mg Paracetamol 3% (2 mL) |
|---|---|---|---|---|---|
| Age, Continuous | 46.1 years STANDARD_DEVIATION 10.9 | 42.85 years STANDARD_DEVIATION 13.2 | 45.5 years STANDARD_DEVIATION 13.6 | 40.1 years STANDARD_DEVIATION 12.8 | 39.7 years STANDARD_DEVIATION 15.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 60 Participants | 15 Participants | 15 Participants | 15 Participants |
| Region of Enrollment Switzerland | 15 participants | 15 participants | 15 participants | 15 participants | 15 participants |
| Sex: Female, Male Female | 2 Participants | 8 Participants | 2 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 13 Participants | 52 Participants | 13 Participants | 13 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 3 / 15 | 0 / 15 | 4 / 15 | 3 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 |
Outcome results
Primary
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)
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 30 mg Paracetamol 3% (1 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 4 hours after NIMP | 6.8 score on a scale | Standard Deviation 8.3 |
| 30 mg Paracetamol 3% (1 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | before discharge | 3.7 score on a scale | Standard Deviation 4.7 |
| 30 mg Paracetamol 3% (1 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 3 hours after NIMP | 21 score on a scale | Standard Deviation 27.7 |
| 30 mg Paracetamol 3% (1 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | baseline | 9.6 score on a scale | Standard Deviation 20 |
| 30 mg Paracetamol 3% (1 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 3.5 hours after NIMP | 19.7 score on a scale | Standard Deviation 21.4 |
| 30 mg Paracetamol 3% (1 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 1.25 hour after NIMP | 4.6 score on a scale | Standard Deviation 11.4 |
| 30 mg Paracetamol 3% (1 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 1.50 hour after NIMP | 5.9 score on a scale | Standard Deviation 13.2 |
| 30 mg Paracetamol 3% (1 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 1 hour after NIMP | 0.1 score on a scale | Standard Deviation 0.3 |
| 30 mg Paracetamol 3% (1 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 4.5 hours after NIMP | 2.5 score on a scale | Standard Deviation 3.5 |
| 30 mg Paracetamol 3% (1 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 1.75 hour after NIMP | 9.5 score on a scale | Standard Deviation 16.5 |
| 30 mg Paracetamol 3% (1 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 2 hours after NIMP | 14.1 score on a scale | Standard Deviation 24.6 |
| 30 mg Paracetamol 3% (1 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 2.5 hours after NIMP | 16.9 score on a scale | Standard Deviation 22.8 |
| 60 mg Paracetamol 3% (2 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 1 hour after NIMP | 0.1 score on a scale | Standard Deviation 0.5 |
| 60 mg Paracetamol 3% (2 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 2.5 hours after NIMP | 8.7 score on a scale | Standard Deviation 7.1 |
| 60 mg Paracetamol 3% (2 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 1.50 hour after NIMP | 4.5 score on a scale | Standard Deviation 10.2 |
| 60 mg Paracetamol 3% (2 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 3.5 hours after NIMP | 6.8 score on a scale | Standard Deviation 11.4 |
| 60 mg Paracetamol 3% (2 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 4 hours after NIMP | 13.3 score on a scale | Standard Deviation 18.1 |
| 60 mg Paracetamol 3% (2 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 3 hours after NIMP | 9.6 score on a scale | Standard Deviation 12.8 |
| 60 mg Paracetamol 3% (2 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | baseline | 16.9 score on a scale | Standard Deviation 17.4 |
| 60 mg Paracetamol 3% (2 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 2 hours after NIMP | 17.8 score on a scale | Standard Deviation 19 |
| 60 mg Paracetamol 3% (2 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 1.75 hour after NIMP | 15.1 score on a scale | Standard Deviation 16.3 |
| 60 mg Paracetamol 3% (2 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 1.25 hour after NIMP | 1.9 score on a scale | Standard Deviation 5.1 |
| 60 mg Paracetamol 3% (2 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | before discharge | 4.1 score on a scale | Standard Deviation 5.6 |
| 60 mg Paracetamol 3% (2 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 4.5 hours after NIMP | 0 score on a scale | Standard Deviation 0 |
| 90 mg Paracetamol 3% (3 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 3 hours after NIMP | 7.3 score on a scale | Standard Deviation 13 |
| 90 mg Paracetamol 3% (3 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | baseline | 18.4 score on a scale | Standard Deviation 26.4 |
| 90 mg Paracetamol 3% (3 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 1 hour after NIMP | 3.4 score on a scale | Standard Deviation 11.5 |
| 90 mg Paracetamol 3% (3 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 1.25 hour after NIMP | 6.2 score on a scale | Standard Deviation 13.7 |
| 90 mg Paracetamol 3% (3 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 1.50 hour after NIMP | 16.4 score on a scale | Standard Deviation 23.6 |
| 90 mg Paracetamol 3% (3 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 1.75 hour after NIMP | 21.4 score on a scale | Standard Deviation 24.3 |
| 90 mg Paracetamol 3% (3 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 2 hours after NIMP | 22.8 score on a scale | Standard Deviation 23.2 |
| 90 mg Paracetamol 3% (3 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 2.5 hours after NIMP | 14.7 score on a scale | Standard Deviation 15.8 |
| 90 mg Paracetamol 3% (3 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 3.5 hours after NIMP | 14.2 score on a scale | Standard Deviation 25.7 |
| 90 mg Paracetamol 3% (3 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 4 hours after NIMP | 15.3 score on a scale | Standard Deviation 19.1 |
| 90 mg Paracetamol 3% (3 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 4.5 hours after NIMP | 2 score on a scale | Standard Deviation 2.6 |
| 90 mg Paracetamol 3% (3 mL) | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | before discharge | 2.9 score on a scale | Standard Deviation 4.5 |
| Placebo, 0.9% Saline Solution | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 2 hours after NIMP | 3.9 score on a scale | Standard Deviation 8.7 |
| Placebo, 0.9% Saline Solution | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 1.75 hour after NIMP | 3.6 score on a scale | Standard Deviation 6.1 |
| Placebo, 0.9% Saline Solution | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | baseline | 8.1 score on a scale | Standard Deviation 14.8 |
| Placebo, 0.9% Saline Solution | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 4 hours after NIMP | 0 score on a scale | Standard Deviation 0 |
| Placebo, 0.9% Saline Solution | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 1.50 hour after NIMP | 1.2 score on a scale | Standard Deviation 2.1 |
| Placebo, 0.9% Saline Solution | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 1.25 hour after NIMP | 0.6 score on a scale | Standard Deviation 1.3 |
| Placebo, 0.9% Saline Solution | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | before discharge | 11.3 score on a scale | Standard Deviation 7.7 |
| Placebo, 0.9% Saline Solution | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 4.5 hours after NIMP | 0 score on a scale | Standard Deviation 0 |
| Placebo, 0.9% Saline Solution | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 3 hours after NIMP | 10.4 score on a scale | Standard Deviation 15.4 |
| Placebo, 0.9% Saline Solution | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 2.5 hours after NIMP | 7.2 score on a scale | Standard Deviation 8.2 |
| Placebo, 0.9% Saline Solution | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 1 hour after NIMP | 0 score on a scale | Standard Deviation 0 |
| Placebo, 0.9% Saline Solution | Pain Intensity at Rest Evaluated Using a 0-100 mm VAS | 3.5 hours after NIMP | 11.4 score on a scale | Standard Deviation 16.8 |
Secondary
Maximum Sensory Block
Maximum level of sensory block
Time frame: Intraoperative
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 30 mg Paracetamol 3% (1 mL) | Maximum Sensory Block | T1 | 0 Participants |
| 30 mg Paracetamol 3% (1 mL) | Maximum Sensory Block | T12 | 0 Participants |
| 30 mg Paracetamol 3% (1 mL) | Maximum Sensory Block | T7 | 0 Participants |
| 30 mg Paracetamol 3% (1 mL) | Maximum Sensory Block | S3 | 0 Participants |
| 30 mg Paracetamol 3% (1 mL) | Maximum Sensory Block | T11 | 2 Participants |
| 30 mg Paracetamol 3% (1 mL) | Maximum Sensory Block | T10 | 3 Participants |
| 30 mg Paracetamol 3% (1 mL) | Maximum Sensory Block | T8 | 7 Participants |
| 30 mg Paracetamol 3% (1 mL) | Maximum Sensory Block | S2 | 0 Participants |
| 30 mg Paracetamol 3% (1 mL) | Maximum Sensory Block | T9 | 0 Participants |
| 30 mg Paracetamol 3% (1 mL) | Maximum Sensory Block | T3 | 0 Participants |
| 30 mg Paracetamol 3% (1 mL) | Maximum Sensory Block | S5 | 0 Participants |
| 30 mg Paracetamol 3% (1 mL) | Maximum Sensory Block | S1 | 0 Participants |
| 30 mg Paracetamol 3% (1 mL) | Maximum Sensory Block | L5 | 0 Participants |
| 30 mg Paracetamol 3% (1 mL) | Maximum Sensory Block | T4 | 0 Participants |
| 30 mg Paracetamol 3% (1 mL) | Maximum Sensory Block | S4 | 0 Participants |
| 30 mg Paracetamol 3% (1 mL) | Maximum Sensory Block | L4 | 0 Participants |
| 30 mg Paracetamol 3% (1 mL) | Maximum Sensory Block | L3 | 0 Participants |
| 30 mg Paracetamol 3% (1 mL) | Maximum Sensory Block | T5 | 0 Participants |
| 30 mg Paracetamol 3% (1 mL) | Maximum Sensory Block | T2 | 1 Participants |
| 30 mg Paracetamol 3% (1 mL) | Maximum Sensory Block | L2 | 0 Participants |
| 30 mg Paracetamol 3% (1 mL) | Maximum Sensory Block | L1 | 1 Participants |
| 30 mg Paracetamol 3% (1 mL) | Maximum Sensory Block | T6 | 1 Participants |
| 60 mg Paracetamol 3% (2 mL) | Maximum Sensory Block | L5 | 0 Participants |
| 60 mg Paracetamol 3% (2 mL) | Maximum Sensory Block | T1 | 0 Participants |
| 60 mg Paracetamol 3% (2 mL) | Maximum Sensory Block | T2 | 0 Participants |
| 60 mg Paracetamol 3% (2 mL) | Maximum Sensory Block | T3 | 0 Participants |
| 60 mg Paracetamol 3% (2 mL) | Maximum Sensory Block | T4 | 0 Participants |
| 60 mg Paracetamol 3% (2 mL) | Maximum Sensory Block | T5 | 1 Participants |
| 60 mg Paracetamol 3% (2 mL) | Maximum Sensory Block | T6 | 1 Participants |
| 60 mg Paracetamol 3% (2 mL) | Maximum Sensory Block | T7 | 1 Participants |
| 60 mg Paracetamol 3% (2 mL) | Maximum Sensory Block | T8 | 0 Participants |
| 60 mg Paracetamol 3% (2 mL) | Maximum Sensory Block | T9 | 3 Participants |
| 60 mg Paracetamol 3% (2 mL) | Maximum Sensory Block | T10 | 5 Participants |
| 60 mg Paracetamol 3% (2 mL) | Maximum Sensory Block | T11 | 3 Participants |
| 60 mg Paracetamol 3% (2 mL) | Maximum Sensory Block | T12 | 1 Participants |
| 60 mg Paracetamol 3% (2 mL) | Maximum Sensory Block | L1 | 0 Participants |
| 60 mg Paracetamol 3% (2 mL) | Maximum Sensory Block | L2 | 0 Participants |
| 60 mg Paracetamol 3% (2 mL) | Maximum Sensory Block | L3 | 0 Participants |
| 60 mg Paracetamol 3% (2 mL) | Maximum Sensory Block | L4 | 0 Participants |
| 60 mg Paracetamol 3% (2 mL) | Maximum Sensory Block | S1 | 0 Participants |
| 60 mg Paracetamol 3% (2 mL) | Maximum Sensory Block | S2 | 0 Participants |
| 60 mg Paracetamol 3% (2 mL) | Maximum Sensory Block | S3 | 0 Participants |
| 60 mg Paracetamol 3% (2 mL) | Maximum Sensory Block | S4 | 0 Participants |
| 60 mg Paracetamol 3% (2 mL) | Maximum Sensory Block | S5 | 0 Participants |
| 90 mg Paracetamol 3% (3 mL) | Maximum Sensory Block | T6 | 1 Participants |
| 90 mg Paracetamol 3% (3 mL) | Maximum Sensory Block | S3 | 0 Participants |
| 90 mg Paracetamol 3% (3 mL) | Maximum Sensory Block | T12 | 0 Participants |
| 90 mg Paracetamol 3% (3 mL) | Maximum Sensory Block | L1 | 1 Participants |
| 90 mg Paracetamol 3% (3 mL) | Maximum Sensory Block | T5 | 1 Participants |
| 90 mg Paracetamol 3% (3 mL) | Maximum Sensory Block | L2 | 0 Participants |
| 90 mg Paracetamol 3% (3 mL) | Maximum Sensory Block | S5 | 0 Participants |
| 90 mg Paracetamol 3% (3 mL) | Maximum Sensory Block | L3 | 0 Participants |
| 90 mg Paracetamol 3% (3 mL) | Maximum Sensory Block | T4 | 1 Participants |
| 90 mg Paracetamol 3% (3 mL) | Maximum Sensory Block | S4 | 0 Participants |
| 90 mg Paracetamol 3% (3 mL) | Maximum Sensory Block | L4 | 0 Participants |
| 90 mg Paracetamol 3% (3 mL) | Maximum Sensory Block | L5 | 0 Participants |
| 90 mg Paracetamol 3% (3 mL) | Maximum Sensory Block | T3 | 0 Participants |
| 90 mg Paracetamol 3% (3 mL) | Maximum Sensory Block | S1 | 0 Participants |
| 90 mg Paracetamol 3% (3 mL) | Maximum Sensory Block | T1 | 0 Participants |
| 90 mg Paracetamol 3% (3 mL) | Maximum Sensory Block | S2 | 0 Participants |
| 90 mg Paracetamol 3% (3 mL) | Maximum Sensory Block | T8 | 6 Participants |
| 90 mg Paracetamol 3% (3 mL) | Maximum Sensory Block | T9 | 2 Participants |
| 90 mg Paracetamol 3% (3 mL) | Maximum Sensory Block | T2 | 0 Participants |
| 90 mg Paracetamol 3% (3 mL) | Maximum Sensory Block | T10 | 1 Participants |
| 90 mg Paracetamol 3% (3 mL) | Maximum Sensory Block | T7 | 0 Participants |
| 90 mg Paracetamol 3% (3 mL) | Maximum Sensory Block | T11 | 2 Participants |
| Placebo, 0.9% Saline Solution | Maximum Sensory Block | S2 | 0 Participants |
| Placebo, 0.9% Saline Solution | Maximum Sensory Block | L5 | 0 Participants |
| Placebo, 0.9% Saline Solution | Maximum Sensory Block | T10 | 4 Participants |
| Placebo, 0.9% Saline Solution | Maximum Sensory Block | T12 | 1 Participants |
| Placebo, 0.9% Saline Solution | Maximum Sensory Block | T5 | 1 Participants |
| Placebo, 0.9% Saline Solution | Maximum Sensory Block | S3 | 0 Participants |
| Placebo, 0.9% Saline Solution | Maximum Sensory Block | S4 | 0 Participants |
| Placebo, 0.9% Saline Solution | Maximum Sensory Block | L1 | 0 Participants |
| Placebo, 0.9% Saline Solution | Maximum Sensory Block | T9 | 0 Participants |
| Placebo, 0.9% Saline Solution | Maximum Sensory Block | T1 | 0 Participants |
| Placebo, 0.9% Saline Solution | Maximum Sensory Block | S1 | 0 Participants |
| Placebo, 0.9% Saline Solution | Maximum Sensory Block | L2 | 0 Participants |
| Placebo, 0.9% Saline Solution | Maximum Sensory Block | T4 | 1 Participants |
| Placebo, 0.9% Saline Solution | Maximum Sensory Block | T2 | 0 Participants |
| Placebo, 0.9% Saline Solution | Maximum Sensory Block | T7 | 0 Participants |
| Placebo, 0.9% Saline Solution | Maximum Sensory Block | L3 | 0 Participants |
| Placebo, 0.9% Saline Solution | Maximum Sensory Block | T11 | 1 Participants |
| Placebo, 0.9% Saline Solution | Maximum Sensory Block | T8 | 6 Participants |
| Placebo, 0.9% Saline Solution | Maximum Sensory Block | S5 | 0 Participants |
| Placebo, 0.9% Saline Solution | Maximum Sensory Block | L4 | 0 Participants |
| Placebo, 0.9% Saline Solution | Maximum Sensory Block | T3 | 0 Participants |
| Placebo, 0.9% Saline Solution | Maximum Sensory Block | T6 | 1 Participants |
Secondary
Pain at Rest AUClast
AUClast is defined as the area under the pain intensity curve from 0 h up to the last assessment time
Time frame: Up to 24 hours after injection
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Paracetamol 3% (1 mL) | Pain at Rest AUClast | 34 score on a scale*h | Standard Deviation 41.3 |
| 60 mg Paracetamol 3% (2 mL) | Pain at Rest AUClast | 24.7 score on a scale*h | Standard Deviation 15.7 |
| 90 mg Paracetamol 3% (3 mL) | Pain at Rest AUClast | 42 score on a scale*h | Standard Deviation 50.3 |
| Placebo, 0.9% Saline Solution | Pain at Rest AUClast | 15.7 score on a scale*h | Standard Deviation 23.3 |
Secondary
Pain at Rest AUCt1-t2
AUC t1-t2 is defined as the area under the pain intensity curve at the specified time-intervals
Time frame: Up to 4 hours after injection
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 30 mg Paracetamol 3% (1 mL) | Pain at Rest AUCt1-t2 | AUC 0-4 hours | 34.6 score on a scale*h | Standard Deviation 29.6 |
| 30 mg Paracetamol 3% (1 mL) | Pain at Rest AUCt1-t2 | AUC 0-2 hours | 13 score on a scale*h | Standard Deviation 13 |
| 60 mg Paracetamol 3% (2 mL) | Pain at Rest AUCt1-t2 | AUC 0-4 hours | 26 score on a scale*h | Standard Deviation 10.9 |
| 60 mg Paracetamol 3% (2 mL) | Pain at Rest AUCt1-t2 | AUC 0-2 hours | 14.8 score on a scale*h | Standard Deviation 12.5 |
| 90 mg Paracetamol 3% (3 mL) | Pain at Rest AUCt1-t2 | AUC 0-2 hours | 26.4 score on a scale*h | Standard Deviation 30.1 |
| 90 mg Paracetamol 3% (3 mL) | Pain at Rest AUCt1-t2 | AUC 0-4 hours | 92.2 score on a scale*h | Standard Deviation 69.4 |
| Placebo, 0.9% Saline Solution | Pain at Rest AUCt1-t2 | AUC 0-2 hours | 4.4 score on a scale*h | Standard Deviation 7.1 |
| Placebo, 0.9% Saline Solution | Pain at Rest AUCt1-t2 | AUC 0-4 hours | 49.7 score on a scale*h | Standard Deviation 21.7 |
Secondary
Partecipants Received Level 2 Analgesia
Partecipants received Tramadol i.v. 1 mg/kg administration (level 2 analgesia)
Time frame: from surgery day to 24 hours after surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 30 mg Paracetamol 3% (1 mL) | Partecipants Received Level 2 Analgesia | 2 Participants |
| 60 mg Paracetamol 3% (2 mL) | Partecipants Received Level 2 Analgesia | 0 Participants |
| 90 mg Paracetamol 3% (3 mL) | Partecipants Received Level 2 Analgesia | 4 Participants |
| Placebo, 0.9% Saline Solution | Partecipants Received Level 2 Analgesia | 0 Participants |
Secondary
Partecipants to Received Level 1 Analgesia
Partecipants to received Ketorolac i.v. \[Toradol\] 30 mg administration (level 1 analgesia)
Time frame: from surgery day to 24 hours after surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 30 mg Paracetamol 3% (1 mL) | Partecipants to Received Level 1 Analgesia | 6 Participants |
| 60 mg Paracetamol 3% (2 mL) | Partecipants to Received Level 1 Analgesia | 5 Participants |
| 90 mg Paracetamol 3% (3 mL) | Partecipants to Received Level 1 Analgesia | 7 Participants |
| Placebo, 0.9% Saline Solution | Partecipants to Received Level 1 Analgesia | 1 Participants |
Secondary
Percentage of Patients Requiring Analgesia From Surgery End Until Eligibility for Discharge
Percentage of patients requiring analgesia (level 1 or level 2) from surgery end until eligibility for home discharge
Time frame: from surgery day to 24 hours after surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 30 mg Paracetamol 3% (1 mL) | Percentage of Patients Requiring Analgesia From Surgery End Until Eligibility for Discharge | 6 Participants |
| 60 mg Paracetamol 3% (2 mL) | Percentage of Patients Requiring Analgesia From Surgery End Until Eligibility for Discharge | 5 Participants |
| 90 mg Paracetamol 3% (3 mL) | Percentage of Patients Requiring Analgesia From Surgery End Until Eligibility for Discharge | 7 Participants |
| Placebo, 0.9% Saline Solution | Percentage of Patients Requiring Analgesia From Surgery End Until Eligibility for Discharge | 1 Participants |
Secondary
Percentage of Patients Requiring Analgesia in the First 2 h After Surgery End
Percentage of patients requiring analgesia (level 1 or level 2) in the first 2 h after surgery end
Time frame: Form surgery day to 2 hours after surgery end
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 30 mg Paracetamol 3% (1 mL) | Percentage of Patients Requiring Analgesia in the First 2 h After Surgery End | 5 Participants |
| 60 mg Paracetamol 3% (2 mL) | Percentage of Patients Requiring Analgesia in the First 2 h After Surgery End | 3 Participants |
| 90 mg Paracetamol 3% (3 mL) | Percentage of Patients Requiring Analgesia in the First 2 h After Surgery End | 7 Participants |
| Placebo, 0.9% Saline Solution | Percentage of Patients Requiring Analgesia in the First 2 h After Surgery End | 0 Participants |
Secondary
Percentage of Patients Requiring Analgesia in the First 4 h After Surgery End
Percentage of patients requiring analgesia (level 1 or level 2) in the first 4 h after surgery end
Time frame: from surgery day to 4 hours after surgery end
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 30 mg Paracetamol 3% (1 mL) | Percentage of Patients Requiring Analgesia in the First 4 h After Surgery End | 6 Participants |
| 60 mg Paracetamol 3% (2 mL) | Percentage of Patients Requiring Analgesia in the First 4 h After Surgery End | 5 Participants |
| 90 mg Paracetamol 3% (3 mL) | Percentage of Patients Requiring Analgesia in the First 4 h After Surgery End | 7 Participants |
| Placebo, 0.9% Saline Solution | Percentage of Patients Requiring Analgesia in the First 4 h After Surgery End | 1 Participants |
Secondary
Percentage of Patients Requiring Level 1 Analgesia From Surgery End Until Eligibility for Discharge
Percentage of patients requiring level 1 analgesia from surgery end until eligibility for home discharge
Time frame: from surgery day to 24 hours after surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 30 mg Paracetamol 3% (1 mL) | Percentage of Patients Requiring Level 1 Analgesia From Surgery End Until Eligibility for Discharge | 6 Participants |
| 60 mg Paracetamol 3% (2 mL) | Percentage of Patients Requiring Level 1 Analgesia From Surgery End Until Eligibility for Discharge | 5 Participants |
| 90 mg Paracetamol 3% (3 mL) | Percentage of Patients Requiring Level 1 Analgesia From Surgery End Until Eligibility for Discharge | 7 Participants |
| Placebo, 0.9% Saline Solution | Percentage of Patients Requiring Level 1 Analgesia From Surgery End Until Eligibility for Discharge | 1 Participants |
Secondary
Percentage of Patients Requiring Level 2 Analgesia From Surgery End Until Eligibility for Discharge
Percentage of Patients Requiring Level 2 Analgesia From Surgery End Until Eligibility for Home Discharge
Time frame: from surgery day to 24 hours after surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 30 mg Paracetamol 3% (1 mL) | Percentage of Patients Requiring Level 2 Analgesia From Surgery End Until Eligibility for Discharge | 2 Participants |
| 60 mg Paracetamol 3% (2 mL) | Percentage of Patients Requiring Level 2 Analgesia From Surgery End Until Eligibility for Discharge | 0 Participants |
| 90 mg Paracetamol 3% (3 mL) | Percentage of Patients Requiring Level 2 Analgesia From Surgery End Until Eligibility for Discharge | 4 Participants |
| Placebo, 0.9% Saline Solution | Percentage of Patients Requiring Level 2 Analgesia From Surgery End Until Eligibility for Discharge | 0 Participants |
Secondary
Percentage of Patients Requiring Rescue Anaesthesia
Percentage of patients requiring rescue anaesthesia
Time frame: from surgery day to 1 hour after injection
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 30 mg Paracetamol 3% (1 mL) | Percentage of Patients Requiring Rescue Anaesthesia | 14 Participants |
| 60 mg Paracetamol 3% (2 mL) | Percentage of Patients Requiring Rescue Anaesthesia | 15 Participants |
| 90 mg Paracetamol 3% (3 mL) | Percentage of Patients Requiring Rescue Anaesthesia | 15 Participants |
| Placebo, 0.9% Saline Solution | Percentage of Patients Requiring Rescue Anaesthesia | 14 Participants |
Secondary
Percentage of Patients Requiring Supplementary Analgesia, Other Than the Planned Level 1 or 2 Analgesia
Percentage of patients requiring supplementary analgesia, other than the planned level 1 or 2 analgesia
Time frame: from surgery day to 24 hours after surgery
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 30 mg Paracetamol 3% (1 mL) | Percentage of Patients Requiring Supplementary Analgesia, Other Than the Planned Level 1 or 2 Analgesia | level 1 | 6 participants |
| 30 mg Paracetamol 3% (1 mL) | Percentage of Patients Requiring Supplementary Analgesia, Other Than the Planned Level 1 or 2 Analgesia | level 2 | 2 participants |
| 60 mg Paracetamol 3% (2 mL) | Percentage of Patients Requiring Supplementary Analgesia, Other Than the Planned Level 1 or 2 Analgesia | level 2 | 0 participants |
| 60 mg Paracetamol 3% (2 mL) | Percentage of Patients Requiring Supplementary Analgesia, Other Than the Planned Level 1 or 2 Analgesia | level 1 | 5 participants |
| 90 mg Paracetamol 3% (3 mL) | Percentage of Patients Requiring Supplementary Analgesia, Other Than the Planned Level 1 or 2 Analgesia | level 1 | 7 participants |
| 90 mg Paracetamol 3% (3 mL) | Percentage of Patients Requiring Supplementary Analgesia, Other Than the Planned Level 1 or 2 Analgesia | level 2 | 4 participants |
| Placebo, 0.9% Saline Solution | Percentage of Patients Requiring Supplementary Analgesia, Other Than the Planned Level 1 or 2 Analgesia | level 1 | 1 participants |
| Placebo, 0.9% Saline Solution | Percentage of Patients Requiring Supplementary Analgesia, Other Than the Planned Level 1 or 2 Analgesia | level 2 | 0 participants |
Secondary
Time to Ambulation
Time to unassisted ambulation
Time frame: Up to 24 hours after injection
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 30 mg Paracetamol 3% (1 mL) | Time to Ambulation | 139 minutes |
| 60 mg Paracetamol 3% (2 mL) | Time to Ambulation | 115 minutes |
| 90 mg Paracetamol 3% (3 mL) | Time to Ambulation | 125 minutes |
| Placebo, 0.9% Saline Solution | Time to Ambulation | 125 minutes |
Secondary
Time to Eligibility for Discharge
Time to eligibility for home discharge
Time frame: Up to 24 hours after injection
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 30 mg Paracetamol 3% (1 mL) | Time to Eligibility for Discharge | 170 minutes |
| 60 mg Paracetamol 3% (2 mL) | Time to Eligibility for Discharge | 165 minutes |
| 90 mg Paracetamol 3% (3 mL) | Time to Eligibility for Discharge | 170 minutes |
| Placebo, 0.9% Saline Solution | Time to Eligibility for Discharge | 168 minutes |
Secondary
Time to First Postoperative Analgesia (Level 1 or 2)
Postoperatively, patients will be administered an analgesic as needed. Post-operative analgesia could include Ketorolac i.v. \[Toradol\] 30 mg (level 1 analgesia) and/or Tramadol i.v. 1 mg/kg (level 2 analgesia). The administered analgesic (level 1 or 2), analgesic dose and intake frequency will be decided according to the reported surgery-related pain intensity. Post-operatively, patients were administered an analgesic, as needed. Post-operative analgesia could include Ketorolac i.v. \[Toradol\] 30 mg (level 1 analgesia) and/or Tramadol i.v. 1 mg/kg (level 2 analgesia).
Time frame: Up to 24 hours after surgery
Population: Nine (9) patients in D1, 10 in D2, 8 in D3 and 14 in P treatment group did not require postoperative analgesia and were censored in the time to first post-operative analgesia analysis
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 30 mg Paracetamol 3% (1 mL) | Time to First Postoperative Analgesia (Level 1 or 2) | 0-2 hours | 5 Participants |
| 30 mg Paracetamol 3% (1 mL) | Time to First Postoperative Analgesia (Level 1 or 2) | 0-4 hours | 6 Participants |
| 60 mg Paracetamol 3% (2 mL) | Time to First Postoperative Analgesia (Level 1 or 2) | 0-4 hours | 5 Participants |
| 60 mg Paracetamol 3% (2 mL) | Time to First Postoperative Analgesia (Level 1 or 2) | 0-2 hours | 3 Participants |
| 90 mg Paracetamol 3% (3 mL) | Time to First Postoperative Analgesia (Level 1 or 2) | 0-2 hours | 7 Participants |
| 90 mg Paracetamol 3% (3 mL) | Time to First Postoperative Analgesia (Level 1 or 2) | 0-4 hours | 7 Participants |
| Placebo, 0.9% Saline Solution | Time to First Postoperative Analgesia (Level 1 or 2) | 0-2 hours | 0 Participants |
| Placebo, 0.9% Saline Solution | Time to First Postoperative Analgesia (Level 1 or 2) | 0-4 hours | 1 Participants |
Secondary
Time to First Urine
Time to first spontaneous urine voiding
Time frame: Up to 24 hours after injection
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 30 mg Paracetamol 3% (1 mL) | Time to First Urine | 155 minutes |
| 60 mg Paracetamol 3% (2 mL) | Time to First Urine | 140 minutes |
| 90 mg Paracetamol 3% (3 mL) | Time to First Urine | 145 minutes |
| Placebo, 0.9% Saline Solution | Time to First Urine | 150 minutes |
Secondary
Time to Onset of Spinal Block (i.e. Time to Readiness for Surgery)
Spinal block/Readiness for surgery is defined as the presence of an adequate motor block (Bromage's score ≥ 2) and loss of Pinprick sensation, according to the Investigator's opinion. Time to readiness for surgery is defined as the time from the spinal injection (time 0 h) to achievement of readiness for surgery.
Time frame: Up to 20 minutes after injection
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 30 mg Paracetamol 3% (1 mL) | Time to Onset of Spinal Block (i.e. Time to Readiness for Surgery) | 5 minutes |
| 60 mg Paracetamol 3% (2 mL) | Time to Onset of Spinal Block (i.e. Time to Readiness for Surgery) | 5 minutes |
| 90 mg Paracetamol 3% (3 mL) | Time to Onset of Spinal Block (i.e. Time to Readiness for Surgery) | 2 minutes |
| Placebo, 0.9% Saline Solution | Time to Onset of Spinal Block (i.e. Time to Readiness for Surgery) | 5 minutes |
Secondary
Time to Regression of Spinal Block
Time period from spinal injection to the complete regression of sensory block to S1.
Time frame: Up to 4 hours after injection
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 30 mg Paracetamol 3% (1 mL) | Time to Regression of Spinal Block | 100 minutes |
| 60 mg Paracetamol 3% (2 mL) | Time to Regression of Spinal Block | 100 minutes |
| 90 mg Paracetamol 3% (3 mL) | Time to Regression of Spinal Block | 90 minutes |
| Placebo, 0.9% Saline Solution | Time to Regression of Spinal Block | 95 minutes |
Secondary
Time to Sensory Block
Time to maximum level of sensory block (bilateral Pinprick test using a 20-G hypodermic needle)
Time frame: Intraoperative
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 30 mg Paracetamol 3% (1 mL) | Time to Sensory Block | 10 minutes |
| 60 mg Paracetamol 3% (2 mL) | Time to Sensory Block | 10 minutes |
| 90 mg Paracetamol 3% (3 mL) | Time to Sensory Block | 10 minutes |
| Placebo, 0.9% Saline Solution | Time to Sensory Block | 10 minutes |
Secondary
Total Number of Partecipants Receiving Analgesic 1
Total number of partecipants receiving Ketorolac i.v. \[Toradol\] 30 mg
Time frame: From surgery day to 24 hours after surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 30 mg Paracetamol 3% (1 mL) | Total Number of Partecipants Receiving Analgesic 1 | 6 Participants |
| 60 mg Paracetamol 3% (2 mL) | Total Number of Partecipants Receiving Analgesic 1 | 5 Participants |
| 90 mg Paracetamol 3% (3 mL) | Total Number of Partecipants Receiving Analgesic 1 | 7 Participants |
| Placebo, 0.9% Saline Solution | Total Number of Partecipants Receiving Analgesic 1 | 1 Participants |
Secondary
Total Number of Partecipants Receiving Analgesic 2
Total Number of Partecipants Receiving Tramadol i.v. 1 mg/kg
Time frame: from surgery day to 24 hours after surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 30 mg Paracetamol 3% (1 mL) | Total Number of Partecipants Receiving Analgesic 2 | 2 Participants |
| 60 mg Paracetamol 3% (2 mL) | Total Number of Partecipants Receiving Analgesic 2 | 0 Participants |
| 90 mg Paracetamol 3% (3 mL) | Total Number of Partecipants Receiving Analgesic 2 | 4 Participants |
| Placebo, 0.9% Saline Solution | Total Number of Partecipants Receiving Analgesic 2 | 0 Participants |
Other Pre-specified
Number of Participants With Neurological Complications Including TNS
Number of Participants with Neurological Complications Including TNS at 24 h post-dose and at day 7±1
Time frame: From anaesthetic intrathecal injection up to day 7±1 (i.e. 6±1 days after analgesic/anaesthetic IT injection and surgery)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 30 mg Paracetamol 3% (1 mL) | Number of Participants With Neurological Complications Including TNS | 0 Participants |
| 60 mg Paracetamol 3% (2 mL) | Number of Participants With Neurological Complications Including TNS | 0 Participants |
| 90 mg Paracetamol 3% (3 mL) | Number of Participants With Neurological Complications Including TNS | 0 Participants |
| Placebo, 0.9% Saline Solution | Number of Participants With Neurological Complications Including TNS | 0 Participants |