Unplanned Caesarean Section
Conditions
Brief summary
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
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.
Interventions
DRUGChloroprocaine
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.
DRUGRopivacaine
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.
Sponsors
Cross Research S.A.
Sintetica SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| Oximetry | Up to 12 hours after surgery | Maternal pulse oximetry (SpO2) |
Countries
Belgium
Participant flow
Recruitment details
Due to difficulties in enrolling patients, the enrolment stopped prematurely, and only 16 patients were screened and randomised (only at site N. 001).
Participants by arm
| Arm | Count |
|---|---|
| Chloroprocaine 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.
Chloroprocaine: 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. | 8 |
| Ropivacaine 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.
Ropivacaine: 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. | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Chloroprocaine | Total | Ropivacaine |
|---|---|---|---|
| Age, Continuous | 28.8 years STANDARD_DEVIATION 5.6 | 31.05 years STANDARD_DEVIATION 6.55 | 33.3 years STANDARD_DEVIATION 7.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 13 Participants | 6 Participants |
| Region of Enrollment Belgium | 8 participants | 16 participants | 8 participants |
| Sex: Female, Male Female | 8 Participants | 16 Participants | 8 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 5 / 8 | 8 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
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.
Time frame: Up to 1 hour after last epidural injection
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chloroprocaine | Time to the Onset of Anaesthesia | 9 minutes | Standard Deviation 5.8 |
| Ropivacaine | Time to the Onset of Anaesthesia | 9.1 minutes | Standard Deviation 4 |
Secondary
Concomitant Medications
Maternal concomitant medications
Time frame: Up to day 3±1 after surgery
Secondary
Discomfort and Pain During Surgery
Discomfort and pain assessed during surgery through spontaneous patient's reporting and questioning by the Investigator/anaesthesiologist
Time frame: Up to 2 hours after last epidural injection
Secondary
Electrocardiogram
Maternal electrocardiogram
Time frame: Up to 12 hours after surgery
Secondary
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)
Time frame: Up to 12 hours after surgery
Secondary
Foetal Hypoxic Stress
Indication of foetal hypoxic stress
Time frame: Up to 12 hours after surgery
Secondary
Intravenous Fluids
Total volume (ml) of intravenous fluids
Time frame: Up to 12 hours after surgery
Secondary
Maternal Treatment-emergent Adverse Events
Maternal treatment-emergent adverse events, with particular attention to pain (see above), pruritus, nausea, vomiting
Time frame: Up to day 3±1 after surgery
Secondary
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)
Time frame: Up to 1 hrs after last epidural injection
Secondary
Motor Block Assessment
Motor block assessment (modified Bromage scale) at baseline, prior to incision and after surgery
Time frame: Up to 12 hours after surgery
Secondary
Neonatal Adverse Events
Neonatal adverse events
Time frame: Up to day 3±1 after surgery
Secondary
Neonate Apgar
Neonate Apgar scores at 1 and 5 minutes
Time frame: 1 and 5 minutes after birth
Secondary
Oximetry
Maternal pulse oximetry (SpO2)
Time frame: Up to 12 hours after surgery
Secondary
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)
Time frame: Up to 12 hours after surgery
Secondary
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)
Time frame: Up to 12 hours after surgery
Secondary
Proportion of Patients Who Need General Anaesthesia
Proportion of patients who need general anaesthesia
Time frame: Up to 2 hours after last epidural injection
Secondary
Proportion of Patients Who Need Supplementation of Opioids
Proportion of patients who need supplementation of the block intraoperatively with intravenous opioids
Time frame: Up to 2 hours after last epidural injection
Secondary
Proportion of Patients Who Need Top-up Anaesthesia
Proportion of patients who need top-up epidural anaesthesia (same anaesthetic as first epidural injection)
Time frame: Up to 2 hours after last epidural injection
Secondary
Pulse Rate
Maternal pulse rate
Time frame: Up to 12 hours after surgery
Secondary
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)
Time frame: Quality of the block assessed between 10 and 20 minutes after the end of surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chloroprocaine | Quality of the Block | 9.8 units on a scale | Standard Deviation 0.4 |
| Ropivacaine | Quality of the Block | 8.4 units on a scale | Standard Deviation 3.7 |
Secondary
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
Time frame: Up to 1 hour after last epidural injection
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chloroprocaine | Time From T0 to Loss Light Touch Sensation | 9.3 minutes | Standard Deviation 9.2 |
| Ropivacaine | Time From T0 to Loss Light Touch Sensation | 13.3 minutes | Standard Deviation 4.1 |
Secondary
Total Dose of Atropine
Total dose (mg) of atropine
Time frame: Up to 2 hours after last epidural injection
Secondary
Total Dose of Phenylephrine
Total dose (μg) of phenylephrine
Time frame: Up to 2 hours after last epidural injection