Spinal Anaesthesia With Chloroprocaine HCl 1% for Elective Lower Limb Procedures of Short Duration.

Study Overview
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Brief Summary
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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
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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)

Official Title
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Spinal Anaesthesia With Chloroprocaine HCl 1% for Elective Lower Limb Procedures of Short Duration: a Prospective, Randomised, Observer-blind Study in Adult Patients

Conditions
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Short Duration Lower Limb Surgery Via Spinal Anaesthesia

Intervention / Treatment
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* Drug: Chloroprocaine HCl 1%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Body Mass Index (BMI): 18 - 32 kg/m2 inclusive ASA physical status: I-II 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: Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study. Contraindications to spinal anaesthesia. History of neuromuscular diseases to the lower extremities ASA physical status: III-V Further anaesthesia: patients expected to require further anaesthesia Allergy: ascertained or presumptive hypersensitivity to the active principle and/or formulations ingredients; ascertained or presumptive hypersensitivity to the ester type and major anaesthetics 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. 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 Drug, alcohol: history of drug or alcohol abuse Blood donation: blood donations in the 3 months before this study Pregnancy and lactation: missing or positive pregnancy test at screening, pregnant or lactating women 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3 mL Chloroprocaine HCl 1%<br>Patients in D1 group will receive a single dose of 3 mL Chloroprocaine HCl 1% (corresponding to 30 mg chloroprocaine HCl) | Drug: Chloroprocaine HCl 1%<br>* Intrathecal Route<br>* Other names: Ampres 1%;|
| Experimental: 4 mL Chloroprocaine HCl 1%<br>Patients in D2 group will receive a single dose of 4 mL Chloroprocaine HCl 1% (corresponding to 40 mg chloroprocaine HCl) | Drug: Chloroprocaine HCl 1%<br>* Intrathecal Route<br>* Other names: Ampres 1%;|
| Experimental: 5 mL Chloroprocaine HCl 1%<br>Patients in D3 group will receive a single dose of 5 mL Chloroprocaine HCl 1% (corresponding to 50 mg chloroprocaine HCl) | Drug: Chloroprocaine HCl 1%<br>* Intrathecal Route<br>* Other names: Ampres 1%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | Up to 5 hours after regression of two dermatomers | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 40 min after spinal injection | 
| Time to Onset of Motor Block | Time period from spinal injection (time 0 h) to achievement of motor block | Up to 40 min after spinal injection | 
| 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 | Up to 40 min after spinal injection | 
| 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) | Time period from spinal injection (time 0 h) to the time when sensitive perception has returned to S1 | Up to 5 h after regression of two dermatomers | 
| 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) | Up to 5 h after regression of two dermatomers | 
| Time to Unassisted Ambulation | Time period from spinal injection (time 0 h) to the time when the patient can walk unassisted | Up to 5 h after regression of two dermatomers | 
| Sensory Block Metameric Level | Metameric level of sensory block assessed from spinal injection (time 0 h) until regression of sensory block to S1 | Up to 5 h after regression of two dermatomers | 
| Maximum Level of Sensory Block | Maximum metameric level of sensory block (decreased or absent sensation) achieved | Up to 1 h and 40 min after readiness for surgery | 
| 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) | Up to 1 h and 40 min after readiness for surgery | 
| 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 | Up to 5 h after regression of two dermatomers | 
| 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 | Expected up to 24 hrs post surgery | 
| 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 | Expected up to 24 hrs post surgery | 
| Time to First Post-operative Analgesia | Time from spinal injection (time 0 h) to first post-operative analgesia | Expected up to 24 hrs post surgery | 
| 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 | Time period from spinal injection ( time 0 h) to the first time when the patient can pass urine unassisted | at the time of first urine voiding post surgery | 
| Treatment-emergent Adverse Events (TEAEs) | All AEs occurring or worsening after the dose of IMP | Up to Day 6 +/- 1 after spinal puncture | 
| 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 | Number of patients with pain at the site of injection and at the site of surgery | Up to Day 6 +/- 1 after spinal puncture | 
| Heart Rate | The following normal ranges Heart Rate parameters will be used: 50-90 beats/min | Expected up to 24 hrs post surgery | 
| 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 | Expected up to 24 hrs post surgery | 
| SpO2 | The following normal ranges SpO2 parameters will be used: Peripheral Oxygen Saturation: ≥ 95% | Expected up to 24 hrs post surgery |