Short Duration Lower Limb Surgery Via Spinal Anaesthesia
Conditions
Brief summary
This study evaluate the effect of 3 doses of Chloroprocaine HCl 1% (30, 40 and 50 mg) for spinal anaesthesia in adult patients undergoing short duration elective surgery of the lower limb. Patients undergoing elective short-duration lower limb surgery will be randomised into 3 treatment groups (15 patients per group) to receive one of the 3 single doses of Chloroprocaine HCl 1%, i.e. either D1, D2 or D3, via intrathecal injection.
Detailed description
To evaluate the efficacy of the three Chloroprocaine HCl 1% doses (i.e. D1, D2 and D3) in terms of time to complete regression of spinal block (i.e. end of anaesthesia)
Interventions
DRUGChloroprocaine HCl 1%
Intrathecal Route
Sponsors
Cross S.A.
Sintetica SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Sex, age and surgery: male/female patients, 18-65 years old, scheduled for short duration (less than 40 min) lower limb surgery requiring ≥ T12 metameric level of sensory block 2. Body Mass Index (BMI): 18 - 32 kg/m2 inclusive 3. ASA physical status: I-II 4. Informed consent: signed written informed consent before inclusion in the study 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: III-V 3. Further anaesthesia: patients expected to require further anaesthesia 4. Allergy: ascertained or presumptive hypersensitivity to the active principle and/or formulations ingredients; ascertained or presumptive hypersensitivity to the ester type and major anaesthetics 5. 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 or other neuropathies. 6. 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 7. Drug, alcohol: history of drug or alcohol abuse 8. Blood donation: blood donations in the 3 months before this study 9. Pregnancy and lactation: missing or positive pregnancy test at screening, pregnant or lactating women 10. Chronic pain syndromes: patients with chronic pain syndromes (taking opioids, antidepressants, anticonvulsant agents or chronic analgesic therapy) 11. Medications: medication known to interfere with the extent of spinal blocks for 2 weeks before the start of the study. Hormonal contraceptives for females are allowed.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Regression of Spinal Block | Up to 5 hours after regression of two dermatomers | When Bromage score returns to 0 and sensitive perception returns to S1 To evaluate the efficacy of the three Chloroprocaine HCI 1% doses (i.e. 30 mg, 40 mg e 50 mg) in terms of time to complete regression of spinal block (i.e. end of anaesthesia) Bromage Score is comprised between 1 and 4 (1 equals Free movement of legs and feet while 4 stands for Unable to move legs or feet) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Onset of Motor Block | Up to 40 min after spinal injection | Time period from spinal injection (time 0 h) to achievement of motor block |
| Time to Readiness for Surgery | Up to 40 min after spinal injection | Time period from completion of spinal injection (time 0 h) to achievement of sensory and motor block adequate for surgery, i.e. loss of Pinprick sensation and Bromage's score ≥ 2 at the required metameric level ≥ T12 |
| Time to Regression of Spinal Block | Up to 1 h and 40 min after readiness for surgery | — |
| Time to Resolution of Sensory Block to S1(Min) | Up to 5 h after regression of two dermatomers | Time period from spinal injection (time 0 h) to the time when sensitive perception has returned to S1 |
| Time to Resolution of Motor Block | Up to 5 h after regression of two dermatomers | Time period from spinal injection (time 0 h) to the time when the Bromage score has returned to 0 (Bromage Scale comprises from 1 to 4, where 1 equals Free movement of legs and feet while 4 stands for Unable to move legs or feet) |
| Time to Unassisted Ambulation | Up to 5 h after regression of two dermatomers | Time period from spinal injection (time 0 h) to the time when the patient can walk unassisted |
| Sensory Block Metameric Level | Up to 5 h after regression of two dermatomers | Metameric level of sensory block assessed from spinal injection (time 0 h) until regression of sensory block to S1 |
| Maximum Level of Sensory Block | Up to 1 h and 40 min after readiness for surgery | Maximum metameric level of sensory block (decreased or absent sensation) achieved |
| Time to Maximum Level of Sensory Block | Up to 1 h and 40 min after readiness for surgery | Time period from spinal injection (Tsp; time 0 h) to the time when the maximum metameric level of sensory block is achieved (consider the time of the first of the two consecutive observations with the same level of sensory block) |
| Time to Regression of Two Dermatomers With Respect to the Maximum Level of Sensory Block | Up to 5 h after regression of two dermatomers | Time period from spinal injection (time 0 h) to the time when the sensory block decrease of two dermatomers with respect to the maximum level of sensory block |
| Time to Eligibility for Home Discharge | Expected up to 24 hrs post surgery | Time period from spinal injection (time 0 h) to the time when the criteria from discharge are met, even if according to the hospital procedures the patient is discharged at a later time |
| Time to Onset of Sensory Block (Corresponding to Readiness for Surgery) | Up to 40 min after spinal injection | Time period from spinal injection (time 0 h) to achievement of sensory block The evolution of both sensory and motor blocks, including sensory block metameric level, will be evaluated every 2 min until readiness for surgery, every 5 min until the maximum level is reached (two consecutive observations with the same level of sensory block) and then every 5 min until regression of two dermatomers with respect to the maximum level of sensory block. |
| Time to First Post-operative Analgesia | Expected up to 24 hrs post surgery | Time from spinal injection (time 0 h) to first post-operative analgesia |
| Time to Administration of Rescue Anaesthesia or Rescue Analgesia | Expected up to 24 hrs post surgery | — |
| Concentration of 2-chloro-4-aminobenzoic Acid (CABA) in Plasma | at pre-dose, 5, 10, 30 and 60 min after spinal puncture | — |
| Excretion of 2-chloro-4-aminobenzoic Acid (CABA) in Urine | at the time of first urine voiding post surgery | Time period from spinal injection ( time 0 h) to the first time when the patient can pass urine unassisted |
| Treatment-emergent Adverse Events (TEAEs) | Up to Day 6 +/- 1 after spinal puncture | All AEs occurring or worsening after the dose of IMP |
| Transient Neurological Symptoms (TNS) | Up to Day 6 +/- 1 after spinal puncture | — |
| Pain Assessment at the Site of Injection and at the Site of Surgery | Up to Day 6 +/- 1 after spinal puncture | Number of patients with pain at the site of injection and at the site of surgery |
| Heart Rate | Expected up to 24 hrs post surgery | The following normal ranges Heart Rate parameters will be used: 50-90 beats/min |
| Blood Pressure | Expected up to 24 hrs post surgery | The following normal ranges Systolic and Diastolic Blood Pressure parameters will be used: Systolic Blood Pressure: 100-139 mmHg Diastolic Blood Pressure: 50-89 mmHg |
| SpO2 | Expected up to 24 hrs post surgery | The following normal ranges SpO2 parameters will be used: Peripheral Oxygen Saturation: ≥ 95% |
| Time to First Spontaneous Urine Voiding | Expected up to 24 hrs post surgery | Time period from spinal injection ( time 0 h) to the first time when the patient can pass urine unassisted |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 3 mL Chloroprocaine HCl 1% Patients in D1 group will receive a single dose of 3 mL Chloroprocaine HCl 1% (corresponding to 30 mg chloroprocaine HCl)
Chloroprocaine HCl 1%: Intrathecal Route | 15 |
| 4 mL Chloroprocaine HCl 1% Patients in D2 group will receive a single dose of 4 mL Chloroprocaine HCl 1% (corresponding to 40 mg chloroprocaine HCl)
Chloroprocaine HCl 1%: Intrathecal Route | 15 |
| 5 mL Chloroprocaine HCl 1% Patients in D3 group will receive a single dose of 5 mL Chloroprocaine HCl 1% (corresponding to 50 mg chloroprocaine HCl)
Chloroprocaine HCl 1%: Intrathecal Route | 15 |
| Total | 45 |
Baseline characteristics
| Characteristic | 4 mL Chloroprocaine HCl 1% | 5 mL Chloroprocaine HCl 1% | 3 mL Chloroprocaine HCl 1% | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0.0 Participants | 0.0 Participants | 0.0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 15 Participants | 15 Participants | 45 Participants |
| Age, Continuous | 39.4 years STANDARD_DEVIATION 12.5 | 41.5 years STANDARD_DEVIATION 13.9 | 41.0 years STANDARD_DEVIATION 11.7 | 40.6 years STANDARD_DEVIATION 12.5 |
| Region of Enrollment Italy | 15 participants | 15 participants | 15 participants | 45 participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 6 Participants | 18 Participants |
| Sex: Female, Male Male | 9 Participants | 9 Participants | 9 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 15 / 15 | 13 / 15 | 13 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Time to Regression of Spinal Block
When Bromage score returns to 0 and sensitive perception returns to S1 To evaluate the efficacy of the three Chloroprocaine HCI 1% doses (i.e. 30 mg, 40 mg e 50 mg) in terms of time to complete regression of spinal block (i.e. end of anaesthesia) Bromage Score is comprised between 1 and 4 (1 equals Free movement of legs and feet while 4 stands for Unable to move legs or feet)
Time frame: Up to 5 hours after regression of two dermatomers
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 mL Chloroprocaine HCl 1% | Time to Regression of Spinal Block | 40.8 minutes | Standard Deviation 12.1 |
| 4 mL Chloroprocaine HCl 1% | Time to Regression of Spinal Block | 39.4 minutes | Standard Deviation 12.5 |
| 5 mL Chloroprocaine HCl 1% | Time to Regression of Spinal Block | 41.5 minutes | Standard Deviation 13.9 |
Secondary
Blood Pressure
The following normal ranges Systolic and Diastolic Blood Pressure parameters will be used: Systolic Blood Pressure: 100-139 mmHg Diastolic Blood Pressure: 50-89 mmHg
Time frame: Expected up to 24 hrs post surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 3 mL Chloroprocaine HCl 1% | Blood Pressure | Systolic Blood Pressure screening | 120 mmHg | Standard Deviation 12.9 |
| 3 mL Chloroprocaine HCl 1% | Blood Pressure | Systolic Blood Pressure baseline | 116.9 mmHg | Standard Deviation 10.5 |
| 3 mL Chloroprocaine HCl 1% | Blood Pressure | Systolic Blood Pressure discharge | 116.9 mmHg | Standard Deviation 10.9 |
| 3 mL Chloroprocaine HCl 1% | Blood Pressure | Diastolic Blood Pressure screening | 81.5 mmHg | Standard Deviation 12.1 |
| 3 mL Chloroprocaine HCl 1% | Blood Pressure | Diastolic Blood Pressure baseline | 74.5 mmHg | Standard Deviation 10.3 |
| 3 mL Chloroprocaine HCl 1% | Blood Pressure | Diastolic Blood Pressure discharge | 75.5 mmHg | Standard Deviation 12.2 |
| 4 mL Chloroprocaine HCl 1% | Blood Pressure | Diastolic Blood Pressure discharge | 79 mmHg | Standard Deviation 8.1 |
| 4 mL Chloroprocaine HCl 1% | Blood Pressure | Systolic Blood Pressure screening | 126 mmHg | Standard Deviation 21.74 |
| 4 mL Chloroprocaine HCl 1% | Blood Pressure | Diastolic Blood Pressure screening | 78.9 mmHg | Standard Deviation 11.9 |
| 4 mL Chloroprocaine HCl 1% | Blood Pressure | Diastolic Blood Pressure baseline | 79.8 mmHg | Standard Deviation 10.9 |
| 4 mL Chloroprocaine HCl 1% | Blood Pressure | Systolic Blood Pressure baseline | 127.9 mmHg | Standard Deviation 19.7 |
| 4 mL Chloroprocaine HCl 1% | Blood Pressure | Systolic Blood Pressure discharge | 124.7 mmHg | Standard Deviation 14.7 |
| 5 mL Chloroprocaine HCl 1% | Blood Pressure | Systolic Blood Pressure baseline | 125.5 mmHg | Standard Deviation 14.1 |
| 5 mL Chloroprocaine HCl 1% | Blood Pressure | Systolic Blood Pressure discharge | 121.7 mmHg | Standard Deviation 8.9 |
| 5 mL Chloroprocaine HCl 1% | Blood Pressure | Diastolic Blood Pressure discharge | 82 mmHg | Standard Deviation 9.5 |
| 5 mL Chloroprocaine HCl 1% | Blood Pressure | Diastolic Blood Pressure screening | 80.5 mmHg | Standard Deviation 9.9 |
| 5 mL Chloroprocaine HCl 1% | Blood Pressure | Systolic Blood Pressure screening | 121.6 mmHg | Standard Deviation 9.1 |
| 5 mL Chloroprocaine HCl 1% | Blood Pressure | Diastolic Blood Pressure baseline | 79.1 mmHg | Standard Deviation 13.3 |
Secondary
Concentration of 2-chloro-4-aminobenzoic Acid (CABA) in Plasma
Time frame: at pre-dose, 5, 10, 30 and 60 min after spinal puncture
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 3 mL Chloroprocaine HCl 1% | Concentration of 2-chloro-4-aminobenzoic Acid (CABA) in Plasma | 5 minutes post-dose | 16.127 minutes | Standard Deviation 20.108 |
| 3 mL Chloroprocaine HCl 1% | Concentration of 2-chloro-4-aminobenzoic Acid (CABA) in Plasma | 10 minutes post-dose | 41.440 minutes | Standard Deviation 31.778 |
| 3 mL Chloroprocaine HCl 1% | Concentration of 2-chloro-4-aminobenzoic Acid (CABA) in Plasma | 30 minutes post-dose | 57.459 minutes | Standard Deviation 43.773 |
| 3 mL Chloroprocaine HCl 1% | Concentration of 2-chloro-4-aminobenzoic Acid (CABA) in Plasma | 60 minutes post-dose | 47.020 minutes | Standard Deviation 41.381 |
| 4 mL Chloroprocaine HCl 1% | Concentration of 2-chloro-4-aminobenzoic Acid (CABA) in Plasma | 60 minutes post-dose | 53.093 minutes | Standard Deviation 31.803 |
| 4 mL Chloroprocaine HCl 1% | Concentration of 2-chloro-4-aminobenzoic Acid (CABA) in Plasma | 5 minutes post-dose | 20.411 minutes | Standard Deviation 23.037 |
| 4 mL Chloroprocaine HCl 1% | Concentration of 2-chloro-4-aminobenzoic Acid (CABA) in Plasma | 30 minutes post-dose | 67.180 minutes | Standard Deviation 36.899 |
| 4 mL Chloroprocaine HCl 1% | Concentration of 2-chloro-4-aminobenzoic Acid (CABA) in Plasma | 10 minutes post-dose | 38.851 minutes | Standard Deviation 25.492 |
| 5 mL Chloroprocaine HCl 1% | Concentration of 2-chloro-4-aminobenzoic Acid (CABA) in Plasma | 60 minutes post-dose | 78.380 minutes | Standard Deviation 48.403 |
| 5 mL Chloroprocaine HCl 1% | Concentration of 2-chloro-4-aminobenzoic Acid (CABA) in Plasma | 10 minutes post-dose | 75.833 minutes | Standard Deviation 67.635 |
| 5 mL Chloroprocaine HCl 1% | Concentration of 2-chloro-4-aminobenzoic Acid (CABA) in Plasma | 30 minutes post-dose | 97.647 minutes | Standard Deviation 61.704 |
| 5 mL Chloroprocaine HCl 1% | Concentration of 2-chloro-4-aminobenzoic Acid (CABA) in Plasma | 5 minutes post-dose | 24.887 minutes | Standard Deviation 20.34 |
Secondary
Excretion of 2-chloro-4-aminobenzoic Acid (CABA) in Urine
Time period from spinal injection ( time 0 h) to the first time when the patient can pass urine unassisted
Time frame: at the time of first urine voiding post surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 mL Chloroprocaine HCl 1% | Excretion of 2-chloro-4-aminobenzoic Acid (CABA) in Urine | 1217.7 ng/mL | Standard Deviation 627.8 |
| 4 mL Chloroprocaine HCl 1% | Excretion of 2-chloro-4-aminobenzoic Acid (CABA) in Urine | 1827.9 ng/mL | Standard Deviation 904.1 |
| 5 mL Chloroprocaine HCl 1% | Excretion of 2-chloro-4-aminobenzoic Acid (CABA) in Urine | 2103.5 ng/mL | Standard Deviation 1537.5 |
Secondary
Heart Rate
The following normal ranges Heart Rate parameters will be used: 50-90 beats/min
Time frame: Expected up to 24 hrs post surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 3 mL Chloroprocaine HCl 1% | Heart Rate | baseline | 63.1 beats/min | Standard Deviation 9.4 |
| 3 mL Chloroprocaine HCl 1% | Heart Rate | screening | 62.2 beats/min | Standard Deviation 8.5 |
| 3 mL Chloroprocaine HCl 1% | Heart Rate | discharge | 64.9 beats/min | Standard Deviation 7 |
| 4 mL Chloroprocaine HCl 1% | Heart Rate | baseline | 71 beats/min | Standard Deviation 14 |
| 4 mL Chloroprocaine HCl 1% | Heart Rate | screening | 67.5 beats/min | Standard Deviation 11.4 |
| 4 mL Chloroprocaine HCl 1% | Heart Rate | discharge | 66.9 beats/min | Standard Deviation 10 |
| 5 mL Chloroprocaine HCl 1% | Heart Rate | screening | 70.7 beats/min | Standard Deviation 8.6 |
| 5 mL Chloroprocaine HCl 1% | Heart Rate | discharge | 67 beats/min | Standard Deviation 8 |
| 5 mL Chloroprocaine HCl 1% | Heart Rate | baseline | 71.7 beats/min | Standard Deviation 9.2 |
Secondary
Maximum Level of Sensory Block
Maximum metameric level of sensory block (decreased or absent sensation) achieved
Time frame: Up to 1 h and 40 min after readiness for surgery
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 3 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | T10 | 3 participants |
| 3 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | T12 | 3 participants |
| 3 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | T4 | 3 participants |
| 3 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | L1 | 1 participants |
| 3 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | T6 | 0 participants |
| 3 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | T2 | 0 participants |
| 3 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | T7 | 1 participants |
| 3 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | T3 | 1 participants |
| 3 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | T8 | 3 participants |
| 4 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | T7 | 0 participants |
| 4 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | T10 | 1 participants |
| 4 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | T2 | 2 participants |
| 4 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | T6 | 1 participants |
| 4 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | T12 | 5 participants |
| 4 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | T8 | 3 participants |
| 4 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | T3 | 0 participants |
| 4 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | L1 | 1 participants |
| 4 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | T4 | 2 participants |
| 5 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | L1 | 0 participants |
| 5 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | T2 | 2 participants |
| 5 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | T3 | 1 participants |
| 5 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | T6 | 4 participants |
| 5 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | T7 | 1 participants |
| 5 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | T8 | 2 participants |
| 5 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | T10 | 3 participants |
| 5 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | T12 | 1 participants |
| 5 mL Chloroprocaine HCl 1% | Maximum Level of Sensory Block | T4 | 1 participants |
Secondary
Pain Assessment at the Site of Injection and at the Site of Surgery
Number of patients with pain at the site of injection and at the site of surgery
Time frame: Up to Day 6 +/- 1 after spinal puncture
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 3 mL Chloroprocaine HCl 1% | Pain Assessment at the Site of Injection and at the Site of Surgery | Immediately after regression of spinal block | 0 participants |
| 3 mL Chloroprocaine HCl 1% | Pain Assessment at the Site of Injection and at the Site of Surgery | discharge | 0 participants |
| 3 mL Chloroprocaine HCl 1% | Pain Assessment at the Site of Injection and at the Site of Surgery | day 2 | 14 participants |
| 3 mL Chloroprocaine HCl 1% | Pain Assessment at the Site of Injection and at the Site of Surgery | day 7 | 15 participants |
| 4 mL Chloroprocaine HCl 1% | Pain Assessment at the Site of Injection and at the Site of Surgery | day 7 | 15 participants |
| 4 mL Chloroprocaine HCl 1% | Pain Assessment at the Site of Injection and at the Site of Surgery | Immediately after regression of spinal block | 0 participants |
| 4 mL Chloroprocaine HCl 1% | Pain Assessment at the Site of Injection and at the Site of Surgery | day 2 | 15 participants |
| 4 mL Chloroprocaine HCl 1% | Pain Assessment at the Site of Injection and at the Site of Surgery | discharge | 0 participants |
| 5 mL Chloroprocaine HCl 1% | Pain Assessment at the Site of Injection and at the Site of Surgery | day 7 | 15 participants |
| 5 mL Chloroprocaine HCl 1% | Pain Assessment at the Site of Injection and at the Site of Surgery | discharge | 0 participants |
| 5 mL Chloroprocaine HCl 1% | Pain Assessment at the Site of Injection and at the Site of Surgery | day 2 | 15 participants |
| 5 mL Chloroprocaine HCl 1% | Pain Assessment at the Site of Injection and at the Site of Surgery | Immediately after regression of spinal block | 0 participants |
Secondary
Sensory Block Metameric Level
Metameric level of sensory block assessed from spinal injection (time 0 h) until regression of sensory block to S1
Time frame: Up to 5 h after regression of two dermatomers
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 3 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | T6 | 0 participants |
| 3 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | L1 | 1 participants |
| 3 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | T8 | 3 participants |
| 3 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | T7 | 1 participants |
| 3 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | T2 | 0 participants |
| 3 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | T12 | 3 participants |
| 3 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | T4 | 3 participants |
| 3 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | T3 | 1 participants |
| 3 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | T10 | 3 participants |
| 4 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | T7 | 0 participants |
| 4 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | T2 | 2 participants |
| 4 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | T3 | 0 participants |
| 4 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | T4 | 2 participants |
| 4 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | T6 | 1 participants |
| 4 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | T8 | 3 participants |
| 4 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | T10 | 1 participants |
| 4 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | T12 | 5 participants |
| 4 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | L1 | 1 participants |
| 5 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | T4 | 1 participants |
| 5 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | T2 | 2 participants |
| 5 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | T10 | 3 participants |
| 5 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | T3 | 1 participants |
| 5 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | L1 | 0 participants |
| 5 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | T7 | 1 participants |
| 5 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | T6 | 4 participants |
| 5 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | T12 | 1 participants |
| 5 mL Chloroprocaine HCl 1% | Sensory Block Metameric Level | T8 | 2 participants |
Secondary
SpO2
The following normal ranges SpO2 parameters will be used: Peripheral Oxygen Saturation: ≥ 95%
Time frame: Expected up to 24 hrs post surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 3 mL Chloroprocaine HCl 1% | SpO2 | baseline | 99.4 percentage | Standard Deviation 0.91 |
| 3 mL Chloroprocaine HCl 1% | SpO2 | screening | 99.7 percentage | Standard Deviation 0.96 |
| 3 mL Chloroprocaine HCl 1% | SpO2 | discharge | 99.33 percentage | Standard Deviation 0.72 |
| 4 mL Chloroprocaine HCl 1% | SpO2 | baseline | 99.13 percentage | Standard Deviation 0.83 |
| 4 mL Chloroprocaine HCl 1% | SpO2 | screening | 99.13 percentage | Standard Deviation 1.25 |
| 4 mL Chloroprocaine HCl 1% | SpO2 | discharge | 99.33 percentage | Standard Deviation 0.9 |
| 5 mL Chloroprocaine HCl 1% | SpO2 | screening | 98.53 percentage | Standard Deviation 1.36 |
| 5 mL Chloroprocaine HCl 1% | SpO2 | discharge | 99 percentage | Standard Deviation 1.07 |
| 5 mL Chloroprocaine HCl 1% | SpO2 | baseline | 98.53 percentage | Standard Deviation 1.51 |
Secondary
Time to Administration of Rescue Anaesthesia or Rescue Analgesia
Time frame: Expected up to 24 hrs post surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 mL Chloroprocaine HCl 1% | Time to Administration of Rescue Anaesthesia or Rescue Analgesia | 0.717 hours | Standard Deviation 0.397 |
| 4 mL Chloroprocaine HCl 1% | Time to Administration of Rescue Anaesthesia or Rescue Analgesia | 0.315 hours | Standard Deviation 0.049 |
| 5 mL Chloroprocaine HCl 1% | Time to Administration of Rescue Anaesthesia or Rescue Analgesia | 0 hours | Standard Deviation 0 |
Secondary
Time to Eligibility for Home Discharge
Time period from spinal injection (time 0 h) to the time when the criteria from discharge are met, even if according to the hospital procedures the patient is discharged at a later time
Time frame: Expected up to 24 hrs post surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 mL Chloroprocaine HCl 1% | Time to Eligibility for Home Discharge | 3.021 hours | Standard Deviation 1.012 |
| 4 mL Chloroprocaine HCl 1% | Time to Eligibility for Home Discharge | 3.545 hours | Standard Deviation 1.281 |
| 5 mL Chloroprocaine HCl 1% | Time to Eligibility for Home Discharge | 3.530 hours | Standard Deviation 0.887 |
Secondary
Time to First Post-operative Analgesia
Time from spinal injection (time 0 h) to first post-operative analgesia
Time frame: Expected up to 24 hrs post surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 mL Chloroprocaine HCl 1% | Time to First Post-operative Analgesia | 8.186 hours | Standard Deviation 10.815 |
| 4 mL Chloroprocaine HCl 1% | Time to First Post-operative Analgesia | 2.928 hours | Standard Deviation 1.228 |
| 5 mL Chloroprocaine HCl 1% | Time to First Post-operative Analgesia | 2.988 hours | Standard Deviation 1.167 |
Secondary
Time to First Spontaneous Urine Voiding
Time period from spinal injection ( time 0 h) to the first time when the patient can pass urine unassisted
Time frame: Expected up to 24 hrs post surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 mL Chloroprocaine HCl 1% | Time to First Spontaneous Urine Voiding | 2.530 hours | Standard Deviation 0.761 |
| 4 mL Chloroprocaine HCl 1% | Time to First Spontaneous Urine Voiding | 3.361 hours | Standard Deviation 1.12 |
| 5 mL Chloroprocaine HCl 1% | Time to First Spontaneous Urine Voiding | 3.067 hours | Standard Deviation 0.755 |
Secondary
Time to Maximum Level of Sensory Block
Time period from spinal injection (Tsp; time 0 h) to the time when the maximum metameric level of sensory block is achieved (consider the time of the first of the two consecutive observations with the same level of sensory block)
Time frame: Up to 1 h and 40 min after readiness for surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 mL Chloroprocaine HCl 1% | Time to Maximum Level of Sensory Block | 0.224 minutes | Standard Deviation 0.14 |
| 4 mL Chloroprocaine HCl 1% | Time to Maximum Level of Sensory Block | 0.235 minutes | Standard Deviation 0.077 |
| 5 mL Chloroprocaine HCl 1% | Time to Maximum Level of Sensory Block | 0.234 minutes | Standard Deviation 0.098 |
Secondary
Time to Onset of Motor Block
Time period from spinal injection (time 0 h) to achievement of motor block
Time frame: Up to 40 min after spinal injection
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 mL Chloroprocaine HCl 1% | Time to Onset of Motor Block | 6.3 minutes | Standard Deviation 3.2 |
| 4 mL Chloroprocaine HCl 1% | Time to Onset of Motor Block | 6 minutes | Standard Deviation 3.3 |
| 5 mL Chloroprocaine HCl 1% | Time to Onset of Motor Block | 4.4 minutes | Standard Deviation 2.3 |
Secondary
Time to Onset of Sensory Block (Corresponding to Readiness for Surgery)
Time period from spinal injection (time 0 h) to achievement of sensory block The evolution of both sensory and motor blocks, including sensory block metameric level, will be evaluated every 2 min until readiness for surgery, every 5 min until the maximum level is reached (two consecutive observations with the same level of sensory block) and then every 5 min until regression of two dermatomers with respect to the maximum level of sensory block.
Time frame: Up to 40 min after spinal injection
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 mL Chloroprocaine HCl 1% | Time to Onset of Sensory Block (Corresponding to Readiness for Surgery) | 5.4 minutes | Standard Deviation 3 |
| 4 mL Chloroprocaine HCl 1% | Time to Onset of Sensory Block (Corresponding to Readiness for Surgery) | 6.6 minutes | Standard Deviation 3.4 |
| 5 mL Chloroprocaine HCl 1% | Time to Onset of Sensory Block (Corresponding to Readiness for Surgery) | 4.8 minutes | Standard Deviation 2 |
Secondary
Time to Readiness for Surgery
Time period from completion of spinal injection (time 0 h) to achievement of sensory and motor block adequate for surgery, i.e. loss of Pinprick sensation and Bromage's score ≥ 2 at the required metameric level ≥ T12
Time frame: Up to 40 min after spinal injection
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 mL Chloroprocaine HCl 1% | Time to Readiness for Surgery | 8 minutes | Standard Deviation 4.1 |
| 4 mL Chloroprocaine HCl 1% | Time to Readiness for Surgery | 7.9 minutes | Standard Deviation 4.7 |
| 5 mL Chloroprocaine HCl 1% | Time to Readiness for Surgery | 5.3 minutes | Standard Deviation 2 |
Secondary
Time to Regression of Spinal Block
Time frame: Up to 1 h and 40 min after readiness for surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 mL Chloroprocaine HCl 1% | Time to Regression of Spinal Block | 1.761 hours | Standard Deviation 0.348 |
| 4 mL Chloroprocaine HCl 1% | Time to Regression of Spinal Block | 2.127 hours | Standard Deviation 0.457 |
| 5 mL Chloroprocaine HCl 1% | Time to Regression of Spinal Block | 2.229 hours | Standard Deviation 0.379 |
Secondary
Time to Regression of Two Dermatomers With Respect to the Maximum Level of Sensory Block
Time period from spinal injection (time 0 h) to the time when the sensory block decrease of two dermatomers with respect to the maximum level of sensory block
Time frame: Up to 5 h after regression of two dermatomers
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 mL Chloroprocaine HCl 1% | Time to Regression of Two Dermatomers With Respect to the Maximum Level of Sensory Block | 0.687 hours | Standard Deviation 0.361 |
| 4 mL Chloroprocaine HCl 1% | Time to Regression of Two Dermatomers With Respect to the Maximum Level of Sensory Block | 0.851 hours | Standard Deviation 0.468 |
| 5 mL Chloroprocaine HCl 1% | Time to Regression of Two Dermatomers With Respect to the Maximum Level of Sensory Block | 0.695 hours | Standard Deviation 0.29 |
Secondary
Time to Resolution of Motor Block
Time period from spinal injection (time 0 h) to the time when the Bromage score has returned to 0 (Bromage Scale comprises from 1 to 4, where 1 equals Free movement of legs and feet while 4 stands for Unable to move legs or feet)
Time frame: Up to 5 h after regression of two dermatomers
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 mL Chloroprocaine HCl 1% | Time to Resolution of Motor Block | 2.662 hours | Standard Deviation 0.789 |
| 4 mL Chloroprocaine HCl 1% | Time to Resolution of Motor Block | 3.361 hours | Standard Deviation 1.12 |
| 5 mL Chloroprocaine HCl 1% | Time to Resolution of Motor Block | 3.213 hours | Standard Deviation 0.856 |
Secondary
Time to Resolution of Sensory Block to S1(Min)
Time period from spinal injection (time 0 h) to the time when sensitive perception has returned to S1
Time frame: Up to 5 h after regression of two dermatomers
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 mL Chloroprocaine HCl 1% | Time to Resolution of Sensory Block to S1(Min) | 1.761 hours | Standard Deviation 0.348 |
| 4 mL Chloroprocaine HCl 1% | Time to Resolution of Sensory Block to S1(Min) | 2.127 hours | Standard Deviation 0.457 |
| 5 mL Chloroprocaine HCl 1% | Time to Resolution of Sensory Block to S1(Min) | 2.195 hours | Standard Deviation 0.386 |
Secondary
Time to Unassisted Ambulation
Time period from spinal injection (time 0 h) to the time when the patient can walk unassisted
Time frame: Up to 5 h after regression of two dermatomers
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 mL Chloroprocaine HCl 1% | Time to Unassisted Ambulation | 2.662 hours | Standard Deviation 0.789 |
| 4 mL Chloroprocaine HCl 1% | Time to Unassisted Ambulation | 3.361 hours | Standard Deviation 1.12 |
| 5 mL Chloroprocaine HCl 1% | Time to Unassisted Ambulation | 3.213 hours | Standard Deviation 0.856 |
Secondary
Transient Neurological Symptoms (TNS)
Time frame: Up to Day 6 +/- 1 after spinal puncture
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 3 mL Chloroprocaine HCl 1% | Transient Neurological Symptoms (TNS) | day 2 | 0 participants |
| 3 mL Chloroprocaine HCl 1% | Transient Neurological Symptoms (TNS) | day 7 | 0 participants |
| 4 mL Chloroprocaine HCl 1% | Transient Neurological Symptoms (TNS) | day 2 | 0 participants |
| 4 mL Chloroprocaine HCl 1% | Transient Neurological Symptoms (TNS) | day 7 | 0 participants |
| 5 mL Chloroprocaine HCl 1% | Transient Neurological Symptoms (TNS) | day 2 | 0 participants |
| 5 mL Chloroprocaine HCl 1% | Transient Neurological Symptoms (TNS) | day 7 | 0 participants |
Secondary
Treatment-emergent Adverse Events (TEAEs)
All AEs occurring or worsening after the dose of IMP
Time frame: Up to Day 6 +/- 1 after spinal puncture
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 3 mL Chloroprocaine HCl 1% | Treatment-emergent Adverse Events (TEAEs) | Procedural pain | 14 participants |
| 3 mL Chloroprocaine HCl 1% | Treatment-emergent Adverse Events (TEAEs) | Injection site pain | 2 participants |
| 3 mL Chloroprocaine HCl 1% | Treatment-emergent Adverse Events (TEAEs) | nausea | 0 participants |
| 3 mL Chloroprocaine HCl 1% | Treatment-emergent Adverse Events (TEAEs) | diarrhea | 0 participants |
| 3 mL Chloroprocaine HCl 1% | Treatment-emergent Adverse Events (TEAEs) | vomiting | 0 participants |
| 3 mL Chloroprocaine HCl 1% | Treatment-emergent Adverse Events (TEAEs) | bradycardia | 0 participants |
| 4 mL Chloroprocaine HCl 1% | Treatment-emergent Adverse Events (TEAEs) | bradycardia | 1 participants |
| 4 mL Chloroprocaine HCl 1% | Treatment-emergent Adverse Events (TEAEs) | Procedural pain | 13 participants |
| 4 mL Chloroprocaine HCl 1% | Treatment-emergent Adverse Events (TEAEs) | diarrhea | 1 participants |
| 4 mL Chloroprocaine HCl 1% | Treatment-emergent Adverse Events (TEAEs) | vomiting | 1 participants |
| 4 mL Chloroprocaine HCl 1% | Treatment-emergent Adverse Events (TEAEs) | Injection site pain | 3 participants |
| 4 mL Chloroprocaine HCl 1% | Treatment-emergent Adverse Events (TEAEs) | nausea | 1 participants |
| 5 mL Chloroprocaine HCl 1% | Treatment-emergent Adverse Events (TEAEs) | Injection site pain | 3 participants |
| 5 mL Chloroprocaine HCl 1% | Treatment-emergent Adverse Events (TEAEs) | nausea | 1 participants |
| 5 mL Chloroprocaine HCl 1% | Treatment-emergent Adverse Events (TEAEs) | bradycardia | 0 participants |
| 5 mL Chloroprocaine HCl 1% | Treatment-emergent Adverse Events (TEAEs) | diarrhea | 0 participants |
| 5 mL Chloroprocaine HCl 1% | Treatment-emergent Adverse Events (TEAEs) | Procedural pain | 13 participants |
| 5 mL Chloroprocaine HCl 1% | Treatment-emergent Adverse Events (TEAEs) | vomiting | 0 participants |