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

NCT ID: NCT04657107

Last Updated: 2020-12-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 402 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-01
• Study Completion Date: 2022-07-01

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.

Conditions

Anesthesia; Analgesia; Depression; Cesarean Section; Parturition

Keywords

S-ketamine; efficacy; safety; Postpartum depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Saline group

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);

Group Type: PLACEBO_COMPARATOR

normal saline

Intervention Type: OTHER

Saline group: pregnant women received saline, intravenous drip

K1 group

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);

Group Type: EXPERIMENTAL

S-ketamine

Intervention Type: DRUG

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

K2 group

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);

Group Type: EXPERIMENTAL

S-ketamine

Intervention Type: DRUG

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

Interventions

S-ketamine

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

Intervention Type: DRUG

normal saline

Saline group: pregnant women received saline, intravenous drip

Intervention Type: OTHER

S-ketamine

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

Intervention Type: DRUG

Other Intervention Names

esketamine; physiological saline; esketamine

Eligibility Criteria

Inclusion Criteria

1. ASA II;

2. Parturients voluntarily sign an informed consent form, fully understands the purpose and significance of the study, and voluntarily abides by the clinical study procedure;

3. Subjects who plan to be elected to undergo cesarean section under continuous combined spinal-epidural anesthesia;

4. Age 18 to 40 years;

5. The expected duration of surgery was less than 2h;

6. Prenatal body mass index (BMI) was less than 35kg/m2。

Exclusion Criteria

1. 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);

2. Those who have a history of stroke, cognitive dysfunction, and epilepsy;

3. 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;

4. Pregnancy with other diseases (malignant tumors, hypertension during pregnancy, abnormal thyroid function, etc.);

5. In the non-oxygen state, the peripheral blood oxygen saturation (SpO2) <92%;

6. Subjects whose prolactin is greater than the upper limit of normal during the screening period;

7. 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;

8. The effect of combined spinal-epidural anesthesia is not good, and other anesthetics are needed;

9. People with a history of allergies to various foods and drugs;

10. 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;

11. There is a history of drug abuse and/or alcohol abuse within 1 year before the screening;

12. Participated in other drug or device trials within 3 months before the screening;

13. Subjects judged by the investigator to be unsuitable to participate in this clinical study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

China Health Promotion Foundation

UNKNOWN

Sponsor Role: collaborator

Beijing Haidian Maternal and Child Health Hospital

OTHER

Sponsor Role: collaborator

Obstetrics & Gynecology Hospital of Fudan University

OTHER

Sponsor Role: collaborator

The Fourth Hospital of Shijiazhuang

OTHER

Sponsor Role: collaborator

Changzhi Maternal and Child Health Hospital

UNKNOWN

Sponsor Role: collaborator

Linfen Maternity&Child Healthcare Hospital

UNKNOWN

Sponsor Role: collaborator

Maternal and Child Health Hospital, Jiading District

OTHER

Sponsor Role: collaborator

Tongzhou Maternal and Child Healthcare Hospital of Beijing

UNKNOWN

Sponsor Role: collaborator

Beijing Chaoyang District Maternal and Child Health Care Hospital

UNKNOWN

Sponsor Role: collaborator

Beijing Obstetrics and Gynecology Hospital

OTHER

Sponsor Role: lead

Responsible Party

Mingjun Xu

Chief of Anesthesiology department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lei Wang

Role: PRINCIPAL_INVESTIGATOR

Beijing Haidian Maternal and Child Health Hospital

Shaoqiang Huang

Role: PRINCIPAL_INVESTIGATOR

Obstetrics & Gynecology Hospital of Fudan University

Jin Zhang

Role: PRINCIPAL_INVESTIGATOR

The Fourth Hospital of Shijiazhuang

Yingbin Ren

Role: PRINCIPAL_INVESTIGATOR

Changzhi Maternal and Child Health Hospital

Yong Qin

Role: PRINCIPAL_INVESTIGATOR

Linfen Maternity&Child Healthcare Hospital

Shenghua Li

Role: PRINCIPAL_INVESTIGATOR

Maternal and Child Health Hospital, Jiading District

Zhenhuan Hou

Role: PRINCIPAL_INVESTIGATOR

Tongzhou Maternal and Child Healthcare Hospital of Beijing

Shuyi Miao

Role: PRINCIPAL_INVESTIGATOR

Beijing Chaoyang District Maternal and Child Health Care Hospital

Central Contacts

Mingjun Xu

Role: CONTACT

Phone: 86-13701038959

Email: snake650222@163.com

Other Identifiers

BeijingOGH

Identifier Type: -

Identifier Source: org_study_id