Chloroprocaine 3% - Epidural Anesthesia in Unplanned Caesarean Section

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.

• Chloroprocaine (Drug), also known as Ampres: 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.
• Ropivacaine (Drug), also known as Naropin: 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.

Primary outcomes

• Time to the Onset of Anaesthesia [Up to 1 hour after last epidural injection]: 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.

Secondary outcomes

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

Sex: Female, ages: 18 Years to any

Inclusion Criteria:

1. Informed consent: Signed written informed consent before inclusion in the study (obtained from women fulfilling the criteria, only when effective analgesia has been established)
2. Sex, pregnancy status and age: Labouring women with singleton pregnancy, ≥ 18 years old
3. Epidural catheter: Previously sited epidural catheter
4. ASA physical status: I-II
5. Analgesia: Effective analgesia established following combined spinal epidural analgesia (CSE)
6. Term gestation: ≥ 36 weeks
7. Caesarean section: Unplanned Caesarean section category 2 or 3, according to Lucas Classification
8. Body Mass Index (BMI): ≤ 40 kg/m2
9. 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 epidural anaesthesia
2. ASA physical status: III-V
3. Further anaesthesia: Patients expected to require further anaesthesia
4. Epidural catheter: Epidural catheter failure (epidural catheter replacement required or inability to provide effective analgesia)
5. Pregnancy: Labouring women with multiple pregnancy
6. Caesarean section: Elective Caesarean section
7. Allergy: ascertained or presumptive hypersensitivity to the active principle and /or formulations ingredients; ascertained or presumptive hypersensitivity to the amide and ester-type anaesthetics
8. 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
9. 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
10. 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
11. Drug, alcohol: history of drug or alcohol abuse
12. Plasma cholinesterase: Known plasma cholinesterase deficiency.

Participant flow

Outcome results

• Time to the Onset of Anaesthesia (Primary), Mean, minutes: Chloroprocaine 9 +/- 5.8; Ropivacaine 9.1 +/- 4
• Time From T0 to Loss Light Touch Sensation (Secondary), Mean, minutes: Chloroprocaine 9.3 +/- 9.2; Ropivacaine 13.3 +/- 4.1
• Quality of the Block (Secondary), Mean, units on a scale: Chloroprocaine 9.8 +/- 0.4; Ropivacaine 8.4 +/- 3.7
• Maximum Metameric Level of the Sensory Block (Secondary)
• Motor Block Assessment (Secondary)
• Proportion of Patients Who Need Top-up Anaesthesia (Secondary)
• Proportion of Patients Who Need Supplementation of Opioids (Secondary)
• Proportion of Patients Who Need General Anaesthesia (Secondary)
• Discomfort and Pain During Surgery (Secondary)
• First Breakthrough Pain (Secondary)
• Maternal Treatment-emergent Adverse Events (Secondary)
• Pulse Rate (Secondary)
• Oximetry (Secondary)
• Electrocardiogram (Secondary)
• Total Dose of Phenylephrine (Secondary)
• Total Dose of Atropine (Secondary)
• Intravenous Fluids (Secondary)
• Neonate Apgar (Secondary)
• Foetal Hypoxic Stress (Secondary)
• Pain at the Site of Surgery (Secondary)
• 3 more outcome measures not shown.

Adverse events

Time frame: Maternal AEs will be assessed throughout the study from the signature of the informed consent up to follow-up Visit Day 3±1

Other adverse events by term

• Study Protocol and Statistical Analysis Plan (PDF, 2020-08-07)

• Marc Van de Velde, MD, Principal investigator, Department of Anesthesiology, UZ Leuven, campus Gasthuisberg