Clinical trial NCT04657107: The Efficacy and Safety of S-ketamine in Elective Cesarean Section
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
Overall status: UNKNOWN
Phase: NA
Conditions: Anesthesia
Analgesia
Depression
Cesarean Section
Parturition
Keywords: S-ketamine
efficacy
safety
Postpartum depression
Lead sponsor: Beijing Obstetrics and Gynecology Hospital
Sponsor class: OTHER
Collaborators: name: China Health Promotion Foundation
name: Beijing Haidian Maternal and Child Health Hospital
name: Obstetrics & Gynecology Hospital of Fudan University
name: Fourth Hospital of Shijiazhuang City
name: Changzhi Maternal and Child Health Hospital
name: Linfen Maternity&Child Healthcare Hospital
name: Maternal and Child Health Hospital, Jiading District
name: Tongzhou Maternal and Child Healthcare Hospital of Beijing
name: Beijing Chaoyang District Maternal and Child Health Care Hospital
First posted: 2020-12-08
Enrollment: 402
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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.

Primary outcomes:
measure: Intraoperative anesthesia effect
timeFrame: Day 1
measure: Ramsay Sedation Scale score
timeFrame: Day 1
measure: Clock-in-the-Box(CIB)
timeFrame: Day 0 & Day 2
Secondary outcomes:
measure: PHQ-9
timeFrame: Day 0 & Day 3 & Day 8 & Day 43
measure: Edinburgh Postnatal Depression Scale(EPDS)
timeFrame: Day 3 & Day 8 & Day 43
measure: Apgar score
timeFrame: Day 0
measure: placental transfer of S-ketamine
timeFrame: Day 0
measure: blood gas
timeFrame: Day 0
measure: umbilical arterial (UA)/umbilical venous (UV) ratio
timeFrame: Day 0
Other outcomes:
Locations:
Study officials:
affiliation: Beijing Haidian Maternal and Child Health Hospital
name: Lei Wang
role: PRINCIPAL_INVESTIGATOR
affiliation: Obstetrics & Gynecology Hospital of Fudan University
name: Shaoqiang Huang
role: PRINCIPAL_INVESTIGATOR
affiliation: Fourth Hospital of Shijiazhuang City
name: Jin Zhang
role: PRINCIPAL_INVESTIGATOR
affiliation: Changzhi Maternal and Child Health Hospital
name: Yingbin Ren
role: PRINCIPAL_INVESTIGATOR
affiliation: Linfen Maternity&Child Healthcare Hospital
name: Yong Qin
role: PRINCIPAL_INVESTIGATOR
affiliation: Maternal and Child Health Hospital, Jiading District
name: Shenghua Li
role: PRINCIPAL_INVESTIGATOR
affiliation: Tongzhou Maternal and Child Healthcare Hospital of Beijing
name: Zhenhuan Hou
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Chaoyang District Maternal and Child Health Care Hospital
name: Shuyi Miao
role: PRINCIPAL_INVESTIGATOR
References: