Chloroprocaine 3% - Epidural Anesthesia in Unplanned Caesarean Section

Study Overview
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Brief Summary
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The study evaluate the quality of epidural anaesthesia and the safety of Chloroprocaine HCl 3% compared with Ropivacaine HCl 0.75% in patients with an epidural catheter in situ undergoing unplanned Caesarean section.

Detailed Description
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Labouring women who have an epidural catheter in situ and established analgesia, in need of an unplanned Caesarean section, will be randomly allocated to receive either Chloroprocaine HCl 3% (T-group) or Ropivacaine HCl 0.75% (R-group) epidurally. Prior to the epidural injection, the patient will be transferred to the operating theatre. The local anaesthetic solution will be freshly prepared and 20 mL will be administered by epidural injection, according to the standard hospital procedures, as detailed in the Study Schedule section below. Time T0 is defined as the start time of the first epidural injection of the investigational product. In case of pain or discomfort, a 6 mL epidural top-up of the same anaesthetic, i.e. Chloroprocaine HCl 3% in T-group and Ropivacaine HCl 0.75% in R-group, will be administered. The anaesthesiologist(s) administering the anaesthetic and collecting the data will be blinded with respect to the treatment given to each patient.

Official Title
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Comparison of Epidural Chloroprocaine 3% and Ropivacaine 0.75% for Unplanned Caesarean Section in Labouring Women Who Have an Epidural Catheter in Situ

Conditions
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Unplanned Caesarean Section

Intervention / Treatment
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* Drug: Chloroprocaine
* Drug: Ropivacaine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent: Signed written informed consent before inclusion in the study (obtained from women fulfilling the criteria, only when effective analgesia has been established) Sex, pregnancy status and age: Labouring women with singleton pregnancy, ≥ 18 years old Epidural catheter: Previously sited epidural catheter ASA physical status: I-II Analgesia: Effective analgesia established following combined spinal epidural analgesia (CSE) Term gestation: ≥ 36 weeks Caesarean section: Unplanned Caesarean section category 2 or 3, according to Lucas Classification Body Mass Index (BMI): ≤ 40 kg/m2 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 epidural anaesthesia ASA physical status: III-V Further anaesthesia: Patients expected to require further anaesthesia Epidural catheter: Epidural catheter failure (epidural catheter replacement required or inability to provide effective analgesia) Pregnancy: Labouring women with multiple pregnancy Caesarean section: Elective Caesarean section Allergy: ascertained or presumptive hypersensitivity to the active principle and /or formulations ingredients; ascertained or presumptive hypersensitivity to the amide and ester-type 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 diseases, eclampsia, antepartum haemorrhage, sepsis, blood coagulation disorders, insulin dependent diabetes mellitus, terminal kidney failure Medications: Medication known to interfere with the extent of regional blocks (see chloroprocaine and ropivacaine SmPCs) for 2 weeks before the start of the study 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 Plasma cholinesterase: Known plasma cholinesterase deficiency.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chloroprocaine<br>Chloroprocaine, 20 ml epidural anaesthetic solution administered according to the standard procedures of the hospital. In case of pain or discomfort, a 6 mL epidural top-up will be administered. | Drug: Chloroprocaine<br>* The 20 mL epidural anaesthetic solution will be administered as follows: 5 mL of the study anaesthetic solution will be given epidurally and the block will be assessed after 2 minutes from the first injection using cold, pinprick and touch. Then intrathecal placement will be excluded and a further 15 mL of the study anaesthetic solution will be administered epidurally. Two minutes after the start of the second injection, the sensory block will be re-assessed using cold, pinprick and touch. In case of pain or discomfort a 6 mL epidural top-up of the same anaesthetic will be administered.<br>* Other names: Ampres;|
| Active Comparator: Ropivacaine<br>Ropivacaine, 20 ml epidural anaesthetic solution administered according to the standard procedures of the hospital. In case of pain or discomfort, a 6 mL epidural top-up will be administered. | Drug: Ropivacaine<br>* The 20 mL epidural anaesthetic solution will be administered as follows: 5 mL of the study anaesthetic solution will be given epidurally and the block will be assessed after 2 minutes from the first injection using cold, pinprick and touch. Then intrathecal placement will be excluded and a further 15 mL of the study anaesthetic solution will be administered epidurally. Two minutes after the start of the second injection, the sensory block will be re-assessed using cold, pinprick and touch. In case of pain or discomfort a 6 mL epidural top-up of the same anaesthetic will be administered.<br>* Other names: Naropin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to the Onset of Anaesthesia | The time from T0 (start time of the epidural injection) to complete loss of cold sensation to the metameric level T4 (block to T4), bilateral. | Up to 1 hour after last epidural injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time From T0 to Loss Light Touch Sensation | Time from T0 to loss light touch sensation to the metameric level T5 (block to T5), bilateral | Up to 1 hour after last epidural injection | 
| Quality of the Block | Quality of the block assessed between 10 and 20 min after the end of surgery by the anaesthesiologist and patient together using a 0-10 cm visual analogue scale (VAS; 10=excellent anaesthetic quality, 0=very poor anaesthetic quality) | Quality of the block assessed between 10 and 20 minutes after the end of surgery | 
| Maximum Metameric Level of the Sensory Block | Maximum metameric level of the sensory block assessed by three modalities (complete loss of cold, pinprick and light touch sensation) | Up to 1 hrs after last epidural injection | 
| Motor Block Assessment | Motor block assessment (modified Bromage scale) at baseline, prior to incision and after surgery | Up to 12 hours after surgery | 
| Proportion of Patients Who Need Top-up Anaesthesia | Proportion of patients who need top-up epidural anaesthesia (same anaesthetic as first epidural injection) | Up to 2 hours after last epidural injection | 
| Proportion of Patients Who Need Supplementation of Opioids | Proportion of patients who need supplementation of the block intraoperatively with intravenous opioids | Up to 2 hours after last epidural injection | 
| Proportion of Patients Who Need General Anaesthesia | Proportion of patients who need general anaesthesia | Up to 2 hours after last epidural injection | 
| Discomfort and Pain During Surgery | Discomfort and pain assessed during surgery through spontaneous patient's reporting and questioning by the Investigator/anaesthesiologist | Up to 2 hours after last epidural injection | 
| First Breakthrough Pain | First breakthrough pain assessed by the patient, recorded on a 0-10 cm VAS (0=no pain, 10= most severe pain imaginable) | Up to 12 hours after surgery | 
| Maternal Treatment-emergent Adverse Events | Maternal treatment-emergent adverse events, with particular attention to pain (see above), pruritus, nausea, vomiting | Up to day 3±1 after surgery | 
| Pulse Rate | Maternal pulse rate | Up to 12 hours after surgery | 
| Oximetry | Maternal pulse oximetry (SpO2) | Up to 12 hours after surgery | 
| Electrocardiogram | Maternal electrocardiogram | Up to 12 hours after surgery | 
| Total Dose of Phenylephrine | Total dose (μg) of phenylephrine | Up to 2 hours after last epidural injection | 
| Total Dose of Atropine | Total dose (mg) of atropine | Up to 2 hours after last epidural injection | 
| Intravenous Fluids | Total volume (ml) of intravenous fluids | Up to 12 hours after surgery | 
| Neonate Apgar | Neonate Apgar scores at 1 and 5 minutes | 1 and 5 minutes after birth | 
| Foetal Hypoxic Stress | Indication of foetal hypoxic stress | Up to 12 hours after surgery | 
| Pain at the Site of Surgery | Pain at the site of surgery at final visit/early termination visit, recorded on a 0-10 cm VAS (0=no pain, 10=most severe pain imaginable) | Up to 12 hours after surgery | 
| Pain at the Site of Epidural Injection | Pain at the site of epidural injection at final visit/early termination visit, recorded on a 0-10 cm VAS (0=no pain, 10=severe pain) | Up to 12 hours after surgery | 
| Concomitant Medications | Maternal concomitant medications | Up to day 3±1 after surgery | 
| Neonatal Adverse Events | Neonatal adverse events | Up to day 3±1 after surgery |