Back to results

The Efficacy and Safety of S-ketamine in Elective Cesarean Section (ES-CS)

Primary Purpose

Anesthesia, Analgesia, Depression

Status

Unknown status

Phase

Not Applicable

Locations

Study Type

Interventional

Intervention

S-ketamine

normal saline

S-ketamine

About this trial

This is an interventional prevention trial for Anesthesia focused on measuring S-ketamine, efficacy, safety, Postpartum depression

Eligibility Criteria

18 Years - 40 Years (Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

ASA II;
Parturients voluntarily sign an informed consent form, fully understands the purpose and significance of the study, and voluntarily abides by the clinical study procedure;
Subjects who plan to be elected to undergo cesarean section under continuous combined spinal-epidural anesthesia;
Age 18 to 40 years;
The expected duration of surgery was less than 2h;
Prenatal body mass index (BMI) was less than 35kg/m2。

Exclusion Criteria:

Parturients with contraindications to continuous combined spinal-epidural anesthesia (such as history of central nervous system infection, spinal cord or spinal canal disease or surgery history, systemic infection, skin or soft tissue infection at the puncture site, coagulation dysfunction);
Those who have a history of stroke, cognitive dysfunction, and epilepsy;
Patients with a history of myocardial infarction, angina pectoris, or a serious arrhythmia such as second-degree and above-degree atrioventricular block within 6 months before screening;
Pregnancy with other diseases (malignant tumors, hypertension during pregnancy, abnormal thyroid function, etc.);
In the non-oxygen state, the peripheral blood oxygen saturation (SpO2) <92%;
Subjects whose prolactin is greater than the upper limit of normal during the screening period;
Alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamine transferase (GGT)> 1.5 times than the normal value, and total bilirubin is higher than the upper limit of normal value, and blood creatinine (Cr)>1.2 times than the upper limit of normal value;
The effect of combined spinal-epidural anesthesia is not good, and other anesthetics are needed;
People with a history of allergies to various foods and drugs;
Continuous taking for any reason within 3 months before the screening, including but not limited to: ketamine, non-steroidal anti-inflammatory drugs (aspirin, acetaminophen, indomethacin, diclofenac, ibuprofen, parecoxib) Sodium, etc.), alpha adrenergic receptor agonists (dexmedetomidine hydrochloride, clonidine, etc.), glucocorticoids (dexamethasone hydrochloride, hydrocortisone, methylprednisolone, etc.), antiepileptic ( Carbamazepine, sodium valproate, etc.), sedation (diazepam, estazolam, midazolam, alprazolam, barbital, phenobarbital and chloral hydrate, etc.), Chinese herbal medicine or Chinese patent medicine with pain and sedative effect;
There is a history of drug abuse and/or alcohol abuse within 1 year before the screening;
Participated in other drug or device trials within 3 months before the screening;
Subjects judged by the investigator to be unsuitable to participate in this clinical study.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Arm Label

Saline group

K1 group

K2 group

Arm Description

Parturients were subsequently placed in a supine position with a left lateral tilt (15 ̊). Combined spinal-epidural anesthesia method (CSE) was performed at the L2-L3 or L3-L4 lumbar vertebral interspace, with 10～13mg 0.5% ropivacaine by a needle-through-needle technique. When adequate anesthesia to the T6 dermatome was achieved (Sensory and motor assessments were performed at 1 min intervals using pinprick testing and the modified Bromage score). Parturients received 10ml intravenous normal saline before surgery, If the anesthesia is inadequate, another 5ml 0.5% ropivacaine was given. Morphine hydrochloride 1 mg in saline 10 mL was injected by several times into the epidural space at the end of the operation. After the surgery, their PCA protocol consisted of 150 ug sufentanil and 24ml atropisetron diluted into 150 ml (2ml of basal infusion, a bolus of 0.5ml on demand, "lock-out" interval of 10 min, last for 48 h postoperatively);

Parturients were subsequently placed in a supine position with a left lateral tilt (15 ̊). Combined spinal-epidural anesthesia method (CSE) was performed at the L2-L3 or L3-L4 lumbar vertebral interspace, with 10～13mg 0.5% ropivacaine by a needle-through-needle technique. When adequate anesthesia to the T6 dermatome was achieved (Sensory and motor assessments were performed at 1 min intervals using pinprick testing and the modified Bromage score). Parturients received 10ml intravenous 0.2mg/kg before surgery, If the anesthesia is inadequate, another 5ml 0.5% ropivacaine was given. Morphine hydrochloride 1 mg in saline 10 mL was injected by several times into the epidural space at the end of the operation. After the surgery, their PCA protocol consisted of 150 ug sufentanil and 24ml atropisetron diluted into 150 ml (2ml of basal infusion, a bolus of 0.5ml on demand, "lock-out" interval of 10 min, last for 48 h postoperatively);

Parturients were subsequently placed in a supine position with a left lateral tilt (15 ̊). Combined spinal-epidural anesthesia method (CSE) was performed at the L2-L3 or L3-L4 lumbar vertebral interspace, with 10～13mg 0.5% ropivacaine by a needle-through-needle technique. When adequate anesthesia to the T6 dermatome was achieved (Sensory and motor assessments were performed at 1 min intervals using pinprick testing and the modified Bromage score). Parturients received 10ml intravenous 0.3mg/kg before surgery, If the anesthesia is inadequate, another 5ml 0.5% ropivacaine was given. Morphine hydrochloride 1 mg in saline 10 mL was injected by several times into the epidural space at the end of the operation. After the surgery, their PCA protocol consisted of 150 ug sufentanil and 24ml atropisetron diluted into 150 ml (2ml of basal infusion, a bolus of 0.5ml on demand, "lock-out" interval of 10 min, last for 48 h postoperatively);

Outcomes

Primary Outcome Measures

Intraoperative anesthesia effect

Anesthesia effect is graded I-IV. Level I means that it is very satisfactory, while Level IV means other anesthesia methods are needed to complete the operation. We expect to reach level I.

Ramsay Sedation Scale score

The Ramsay Sedation Scale (RSS) was the first scale to be defined for sedated patients and was designed as a test of rousability. The RSS scores sedation at six different levels, according to how rousable the patient is.

Clock-in-the-Box(CIB)

The Clock-in-the-Box (CIB) is a rapidly administered cognitive screening measure which has been previously validated with cognitive screening and neuropsychological assessments. The CIB is scored on a 0-8 point scale and the total score includes two separate subscale scores. The higher scores reflect better performance.

Secondary Outcome Measures

PHQ-9

PHQ-9 is the major depressive disorder(MDD) module of the full PHQ. Used to provisionally diagnose depression and grade severity of symptoms in general medical and mental health settings. Scores each of the 9 DSM criteria of MDD as "0" (not at all) to "3" (nearly every day), providing a 0-27 severity score. Higher PHQ-9 scores are associated with decreased functional status and increased symptom-related difficulties, sick days, and healthcare utilization.

Edinburgh Postnatal Depression Scale(EPDS)

EPDS is a valuable and efficient way of identifying patients at risk for "perinatal" depression. Mothers who score above 13 are likely to be suffering from a depressive illness of varying severity depression.

Apgar score

The Apgar score is a test given to newborns soon after birth. This test checks a baby's heart rate, muscle tone, and other signs to see if extra medical care or emergency care is needed. The test is usually given twice: once at 1 minute after birth, and again at 5 minutes after birth.

placental transfer of S-ketamine

Placental transfer was evaluated based on the whole blood concentrations of S-ketamine in the maternal and cord blood

blood gas

Blood gases are a group of tests that are performed together to measure the pH and the amount of oxygen (O2) and carbon dioxide (CO2) present in a sample of blood

umbilical arterial (UA)/umbilical venous (UV) ratio

UA/UV ratio was evaluated based on the blood concentrations of S-ketamine in the umbilical arterial and umbilical venous blood

Full Information

NCT ID

NCT04657107

First Posted

December 1, 2020

Last Updated

December 1, 2020

Sponsor

Beijing Obstetrics and Gynecology Hospital

Collaborators

China Health Promotion Foundation, Beijing Haidian Maternal and Child Health Hospital, Obstetrics & Gynecology Hospital of Fudan University, Fourth Hospital of Shijiazhuang City, Changzhi Maternal and Child Health Hospital, Linfen Maternity&Child Healthcare Hospital, Maternal and Child Health Hospital, Jiading District, Tongzhou Maternal and Child Healthcare Hospital of Beijing, Beijing Chaoyang District Maternal and Child Health Care Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04657107

Brief Title

The Efficacy and Safety of S-ketamine in Elective Cesarean Section

Acronym

ES-CS

Official Title

The Efficacy and Safety of S-ketamine in Elective Cesarean Section: a Multi-center, Randomized, Double-blind, Placebo-controlled Clinical Study

Study Type

Interventional

2. Study Status

Record Verification Date

December 2020

Overall Recruitment Status

Unknown status

Study Start Date

December 1, 2020 (Anticipated)

Primary Completion Date

December 15, 2021 (Anticipated)

Study Completion Date

July 1, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Beijing Obstetrics and Gynecology Hospital

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

During the past years, a large number of clinical trials have investigated the use of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist racemic ketamine as an adjunct to local anaesthetics, opioids, or other analgesic agents for the management and prevention of postoperative pain. Actually racemic ketamine not only abolishes peripheral afferent noxious stimulation, but can also prevent the central nociceptor sensitization. S-ketamine, one of two enantiomers of racemic ketamine, has twice the analgesic potency of the racemate. Moreover, S-ketamine shows smaller nervous system and less psychotropic effects than racemic ketamine , which may make the drug more suitable for clinical use. Recently, S-ketamine has been approved to treat refractory depression (TRD) and major depressive disorder (MDD) by the FDA .S-ketamine may have greater clinical significance due to the high rate of maternal depression. Therefore, we plan to explore whether clinical use of S-ketamine can optimize anesthesia protocol and improve maternal prognosis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Anesthesia, Analgesia, Depression, Cesarean Section, Parturition

Keywords

S-ketamine, efficacy, safety, Postpartum depression

7. Study Design

Primary Purpose

Prevention

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

402 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Saline group

Arm Type

Placebo Comparator

Arm Description

Arm Title

K1 group

Arm Type

Experimental

Arm Description

Parturients were subsequently placed in a supine position with a left lateral tilt (15 ̊). Combined spinal-epidural anesthesia method (CSE) was performed at the L2-L3 or L3-L4 lumbar vertebral interspace, with 10～13mg 0.5% ropivacaine by a needle-through-needle technique. When adequate anesthesia to the T6 dermatome was achieved (Sensory and motor assessments were performed at 1 min intervals using pinprick testing and the modified Bromage score). Parturients received 10ml intravenous 0.2mg/kg before surgery, If the anesthesia is inadequate, another 5ml 0.5% ropivacaine was given. Morphine hydrochloride 1 mg in saline 10 mL was injected by several times into the epidural space at the end of the operation. After the surgery, their PCA protocol consisted of 150 ug sufentanil and 24ml atropisetron diluted into 150 ml (2ml of basal infusion, a bolus of 0.5ml on demand, "lock-out" interval of 10 min, last for 48 h postoperatively);

Arm Title

K2 group

Arm Type

Experimental

Arm Description

Parturients were subsequently placed in a supine position with a left lateral tilt (15 ̊). Combined spinal-epidural anesthesia method (CSE) was performed at the L2-L3 or L3-L4 lumbar vertebral interspace, with 10～13mg 0.5% ropivacaine by a needle-through-needle technique. When adequate anesthesia to the T6 dermatome was achieved (Sensory and motor assessments were performed at 1 min intervals using pinprick testing and the modified Bromage score). Parturients received 10ml intravenous 0.3mg/kg before surgery, If the anesthesia is inadequate, another 5ml 0.5% ropivacaine was given. Morphine hydrochloride 1 mg in saline 10 mL was injected by several times into the epidural space at the end of the operation. After the surgery, their PCA protocol consisted of 150 ug sufentanil and 24ml atropisetron diluted into 150 ml (2ml of basal infusion, a bolus of 0.5ml on demand, "lock-out" interval of 10 min, last for 48 h postoperatively);

Intervention Type

Drug

Intervention Name(s)

S-ketamine

Other Intervention Name(s)

esketamine

Intervention Description

K1 group: pregnant women received 0.2mg/kg S-ketamine, intravenous drip;

Intervention Type

Other

Intervention Name(s)

normal saline

Other Intervention Name(s)

physiological saline

Intervention Description

Saline group: pregnant women received saline, intravenous drip

Intervention Type

Drug

Intervention Name(s)

S-ketamine

Other Intervention Name(s)

esketamine

Intervention Description

K2 group: pregnant women received 0.3mg/kg S-ketamine, intravenous drip;

Primary Outcome Measure Information:

Title

Intraoperative anesthesia effect

Description

Anesthesia effect is graded I-IV. Level I means that it is very satisfactory, while Level IV means other anesthesia methods are needed to complete the operation. We expect to reach level I.

Time Frame

Day 1

Title

Ramsay Sedation Scale score

Description

Time Frame

Day 1

Title

Clock-in-the-Box(CIB)

Description

Time Frame

Day 0 & Day 2

Secondary Outcome Measure Information:

Title

PHQ-9

Description

Time Frame

Day 0 & Day 3 & Day 8 & Day 43

Title

Edinburgh Postnatal Depression Scale(EPDS)

Description

Time Frame

Day 3 & Day 8 & Day 43

Title

Apgar score

Description

Time Frame

Day 0

Title

placental transfer of S-ketamine

Description

Placental transfer was evaluated based on the whole blood concentrations of S-ketamine in the maternal and cord blood

Time Frame

Day 0

Title

blood gas

Description

Blood gases are a group of tests that are performed together to measure the pH and the amount of oxygen (O2) and carbon dioxide (CO2) present in a sample of blood

Time Frame

Day 0

Title

umbilical arterial (UA)/umbilical venous (UV) ratio

Description

UA/UV ratio was evaluated based on the blood concentrations of S-ketamine in the umbilical arterial and umbilical venous blood

Time Frame

Day 0

10. Eligibility

Sex

Female

Gender Based

Yes

Gender Eligibility Description

Parturients undergoing elective cesarean section

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: ASA II; Parturients voluntarily sign an informed consent form, fully understands the purpose and significance of the study, and voluntarily abides by the clinical study procedure; Subjects who plan to be elected to undergo cesarean section under continuous combined spinal-epidural anesthesia; Age 18 to 40 years; The expected duration of surgery was less than 2h; Prenatal body mass index (BMI) was less than 35kg/m2。 Exclusion Criteria: Parturients with contraindications to continuous combined spinal-epidural anesthesia (such as history of central nervous system infection, spinal cord or spinal canal disease or surgery history, systemic infection, skin or soft tissue infection at the puncture site, coagulation dysfunction); Those who have a history of stroke, cognitive dysfunction, and epilepsy; Patients with a history of myocardial infarction, angina pectoris, or a serious arrhythmia such as second-degree and above-degree atrioventricular block within 6 months before screening; Pregnancy with other diseases (malignant tumors, hypertension during pregnancy, abnormal thyroid function, etc.); In the non-oxygen state, the peripheral blood oxygen saturation (SpO2) <92%; Subjects whose prolactin is greater than the upper limit of normal during the screening period; Alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamine transferase (GGT)> 1.5 times than the normal value, and total bilirubin is higher than the upper limit of normal value, and blood creatinine (Cr)>1.2 times than the upper limit of normal value; The effect of combined spinal-epidural anesthesia is not good, and other anesthetics are needed; People with a history of allergies to various foods and drugs; Continuous taking for any reason within 3 months before the screening, including but not limited to: ketamine, non-steroidal anti-inflammatory drugs (aspirin, acetaminophen, indomethacin, diclofenac, ibuprofen, parecoxib) Sodium, etc.), alpha adrenergic receptor agonists (dexmedetomidine hydrochloride, clonidine, etc.), glucocorticoids (dexamethasone hydrochloride, hydrocortisone, methylprednisolone, etc.), antiepileptic ( Carbamazepine, sodium valproate, etc.), sedation (diazepam, estazolam, midazolam, alprazolam, barbital, phenobarbital and chloral hydrate, etc.), Chinese herbal medicine or Chinese patent medicine with pain and sedative effect; There is a history of drug abuse and/or alcohol abuse within 1 year before the screening; Participated in other drug or device trials within 3 months before the screening; Subjects judged by the investigator to be unsuitable to participate in this clinical study.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Mingjun Xu

Phone

86-13701038959

snake650222@163.com

Overall Study Officials: