Different Doses of Dexmedetomidine Combined With Esketamine in Women Undergoing Cesarean Delivery

NCT06613243 | Completed Phase 4 DMC

• 1 other identifier: 2024-468
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Esketamine is a commonly used analgesic during cesarean delivery, but may produce transient neuropsychiatric symptoms. Dexmedetomidine has both sedative and analgesic effects. When used in combination with esketamine, dexmedetomidine can reduce esketamine related neuropsychiatric effects after general anesthesia. The investigator speculate that combining low-dose dexmedetomidine with esketamine may also reduce neuropsychiatric adverse effects of esketamine in women undergoing cesarean section. This pilot trial is designed to determine the minimum dose of dexmedetomidine that can effectively prevent neuropsychiatric side effects of antidepressive dose esketamine (0.2mg/kg) in women undergoing cesarean delivery.

Conditions

Cesarean Delivery; Esketamine; Neuropsychiatric Symptoms; Dexmedetomidine

Keywords

cesarean delivery; esketamine; neuropsychiatric symptoms; dexmedetomidine

Outcome Measures

Primary Outcomes (1)

• Incidence of dissociation within 24 hours.

  Dissociative symptoms is assessed with the Clinician-Administered Dissociative States Scale (CADSS; scores range from 0 to 92, with higher score indicating more severe symptoms) at the end of study drug infusion and at 1, 2, and 24 hours after study drug infusion. A CADSS score of \>4 points at any timepoint indicates occurrence of dissociative symptoms.

  Up to 24 hours after study drug infusion.

Secondary Outcomes (4)

• Severity of dissociative symptoms at different timepoints within 24 hours.

  Up to 24 hours after study drug infusion.

• Prevelance of dissociation at different timepoints within 24 hours.

  Up to 24 hours after study drug infusion.

• Incidence of neuropsychiatric adverse events within 24 hours.

  Up to 24 hours after study drug infusion.

• Prevalence of neuropsychiatric adverse events at different timepoints within 24 hours.

  Up to 24 hours after study drug infusion.

Other Outcomes (6)

• Duration of sedation within 24 hours.

  Up to 24 hours after study drug infusion.

• Pain intensity within 7 days postpartum.

  Up 7 days postpartum.

• Proportion of exclusive breastfeeding.

  Up to 7 days postpartum.

Study Arms (4)

Esketamine 0.2 mg/kg

ACTIVE COMPARATOR

Esketamine 0.2 mg/kg is diluted in 20 ml normal saline and infused over 40 minutes after clamping the umbilical cord.

Drug: Esketamine 0.2 mg/kg

Esketamine 0.2 mg/kg + dexmedetomidine 0.1 µg/kg

EXPERIMENTAL

A mixture of esketamine 0.2 mg/kg and dexmedetomidine 0.1 µg/kg is diluted in 20 ml normal saline and infused over 40 minutes after clamping the umbilical cord.

Drug: Esketamine 0.2 mg/kg + dexmedetomidine 0.1 µg/kg

Esketamine 0.2 mg/kg + dexmedetomidine 0.15 µg/kg

EXPERIMENTAL

A mixture of esketamine 0.2 mg/kg and dexmedetomidine 0.15 µg/kg is diluted in 20 ml normal saline and infused over 40 minutes after clamping the umbilical cord.

Drug: Esketamine 0.2 mg/kg + dexmedetomidine 0.15 µg/kg

Esketamine 0.2 mg/kg + dexmedetomidine 0.2 µg/kg

EXPERIMENTAL

A mixture of esketamine 0.2 mg/kg and dexmedetomidine 0.2 µg/kg is diluted in 20 ml normal saline and infused over 40 minutes after clamping the umbilical cord.

Drug: Esketamine 0.2 mg/kg + dexmedetomidine 0.2 µg/kg

Interventions

Esketamine 0.2 mg/kg DRUG

Esketamine 0.2 mg/kg is diluted in 20 ml normal saline and infused over 40 minutes after clamping the umbilical cord.

Esketamine 0.2 mg/kg

Esketamine 0.2 mg/kg + dexmedetomidine 0.1 µg/kg DRUG

A mixture of esketamine 0.2 mg/kg and dexmedetomidine 0.1 µg/kg is diluted in 20 ml normal saline and infused over 40 minutes after clamping the umbilical cord.

Esketamine 0.2 mg/kg + dexmedetomidine 0.1 µg/kg

Esketamine 0.2 mg/kg + dexmedetomidine 0.15 µg/kg DRUG

A mixture of esketamine 0.2 mg/kg and dexmedetomidine 0.15 µg/kg is diluted in 20 ml normal saline and infused over 40 minutes after clamping the umbilical cord.

Esketamine 0.2 mg/kg + dexmedetomidine 0.15 µg/kg

Esketamine 0.2 mg/kg + dexmedetomidine 0.2 µg/kg DRUG

A mixture of esketamine 0.2 mg/kg and dexmedetomidine 0.2 µg/kg is diluted in 20 ml normal saline and infused over 40 minutes after clamping the umbilical cord.

Esketamine 0.2 mg/kg + dexmedetomidine 0.2 µg/kg

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Pregnant women aged ≥18 years.
• Scheduled for elective or emergency cesarean delivery under neuraxial anesthesia.

You may not qualify if:

• A previous history of schizophrenia;
• Severe complications of pregnancy, such as pre-eclampsia, placenta accreta spectrum, or HELLP (intravascular haemolysis, elevated liver enzymes, and low platelet count) syndrome; or American Society of Anesthesiologists classification III or higher;
• Any contraindications to ketamine or esketamine, such as refractory hypertension, severe cardiovascular disease, or hyperthyroidism;
• Any contraindications to dexmedetomidine, such as sick sinus syndrome, severe sinus bradycardia (\<50 beats per minute), or second-degree or above atrioventricular block without pacemaker;
• Other conditions that are considered unsuitable for study participation.

Sponsors & Collaborators

• Peking University First Hospital: lead

Study Sites (1)

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

Location

Related Publications (9)

• Bremner JD, Krystal JH, Putnam FW, Southwick SM, Marmar C, Charney DS, Mazure CM. Measurement of dissociative states with the Clinician-Administered Dissociative States Scale (CADSS). J Trauma Stress. 1998 Jan;11(1):125-36. doi: 10.1023/A:1024465317902.

  PMID: 9479681 BACKGROUND

• Keating GM. Dexmedetomidine: A Review of Its Use for Sedation in the Intensive Care Setting. Drugs. 2015 Jul;75(10):1119-30. doi: 10.1007/s40265-015-0419-5.

  PMID: 26063213 BACKGROUND

• Daly EJ, Singh JB, Fedgchin M, Cooper K, Lim P, Shelton RC, Thase ME, Winokur A, Van Nueten L, Manji H, Drevets WC. Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2018 Feb 1;75(2):139-148. doi: 10.1001/jamapsychiatry.2017.3739.

  PMID: 29282469 BACKGROUND

• Molero P, Ramos-Quiroga JA, Martin-Santos R, Calvo-Sanchez E, Gutierrez-Rojas L, Meana JJ. Antidepressant Efficacy and Tolerability of Ketamine and Esketamine: A Critical Review. CNS Drugs. 2018 May;32(5):411-420. doi: 10.1007/s40263-018-0519-3.

  PMID: 29736744 BACKGROUND

• Lu X, Tang L, Lan H, Li C, Lin H. A Comparison of Intranasal Dexmedetomidine, Esketamine or a Dexmedetomidine-Esketamine Combination for Induction of Anaesthesia in Children: A Randomized Controlled Double-Blind Trial. Front Pharmacol. 2022 Jan 27;12:808930. doi: 10.3389/fphar.2021.808930. eCollection 2021.

  PMID: 35185548 BACKGROUND

• Mello RP, Echegaray MVF, Jesus-Nunes AP, Leal GC, Magnavita GM, Vieira F, Caliman-Fontes AT, Telles M, Guerreiro-Costa LNF, Souza-Marques B, Bandeira ID, Santos-Lima C, Marback RF, Correia-Melo FS, Lacerda ALT, Quarantini LC. Trait dissociation as a predictor of induced dissociation by ketamine or esketamine in treatment-resistant depression: Secondary analysis from a randomized controlled trial. J Psychiatr Res. 2021 Jun;138:576-583. doi: 10.1016/j.jpsychires.2021.05.014. Epub 2021 May 8.

  PMID: 33991996 BACKGROUND

• Zhang Y, Cui F, Ma JH, Wang DX. Mini-dose esketamine-dexmedetomidine combination to supplement analgesia for patients after scoliosis correction surgery: a double-blind randomised trial. Br J Anaesth. 2023 Aug;131(2):385-396. doi: 10.1016/j.bja.2023.05.001. Epub 2023 Jun 9.

  PMID: 37302963 BACKGROUND

• Wang S, Deng CM, Zeng Y, Chen XZ, Li AY, Feng SW, Xu LL, Chen L, Yuan HM, Hu H, Yang T, Han T, Zhang HY, Jiang M, Sun XY, Guo HN, Sessler DI, Wang DX. Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: randomised clinical trial. BMJ. 2024 Apr 10;385:e078218. doi: 10.1136/bmj-2023-078218.

  PMID: 38808490 BACKGROUND

• Yang JR, Li YY, Ran TJ, Lin XY, Xu JY, Zhou SL, Huang PJ. Esketamine Combined with Dexmedetomidine to reduce Visceral Pain During elective Cesarean Section Under Combined Spinal-Epidural Anesthesia: A double-Blind Randomized Controlled Study. Drug Des Devel Ther. 2024 Jun 18;18:2381-2392. doi: 10.2147/DDDT.S460924. eCollection 2024.

  PMID: 38911034 BACKGROUND

MeSH Terms

Interventions

Esketamine; Dexmedetomidine

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Dong-Xin Wang, M.D., PhD.

  Peking University First Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PHD, Professor and Chairman

Model Details: A randomized, double-blind, pilot trial

Study Record Dates

• First Submitted: September 23, 2024
• First Posted: September 25, 2024
• Study Start: October 8, 2024
• Primary Completion: December 2, 2024
• Study Completion: December 9, 2024
• Last Updated: December 30, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)