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

Depression Clinical Trial

— 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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04657107
• Other study ID #: BeijingOGH
• Status: Not yet recruiting
• Phase: N/A
• Start date: December 1, 2020
• Est. completion date: July 1, 2022

Study information

• Verified date: December 2020
• Source: Beijing Obstetrics and Gynecology Hospital
• Contact: Mingjun Xu
• Phone: 86-13701038959
• Email: snake650222[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 402
• Est. completion date: July 1, 2022
• Est. primary completion date: December 15, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Analgesia
• Anesthesia
• Cesarean Section
• Depression
• Parturition

Intervention

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

Other:
• normal saline
Saline group: pregnant women received saline, intravenous drip

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

Locations

Country	Name	City	State
n/a

Sponsors (10)

Lead Sponsor

Collaborator

Beijing Obstetrics and Gynecology Hospital

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Day 1
Primary	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.	Day 1
Primary	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.	Day 0 & Day 2
Secondary	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.	Day 0 & Day 3 & Day 8 & Day 43
Secondary	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.	Day 3 & Day 8 & Day 43
Secondary	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.	Day 0
Secondary	placental transfer of S-ketamine	Placental transfer was evaluated based on the whole blood concentrations of S-ketamine in the maternal and cord blood	Day 0
Secondary	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	Day 0
Secondary	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	Day 0