Ketamine Tolerated Dose for Postpartum Depression and Pain After Cesarean Delivery (PREPARE 1)

Phase 1

Completed

• Conditions: Pain, Postoperative; Depression, Postpartum
• Interventions: Drug: Ketamine (Ketalar) Dose Level 1; Drug: Ketamine (Ketalar) Dose Level 2; Drug: Ketamine (Ketalar) Dose Level 3; Drug: Ketamine (Ketalar) Dose Level 4

• Registration Number: NCT05907213
• Lead Sponsor: Grace Lim, MD, MS

Brief Summary

The purpose of this study is to identify a tolerable dose for postpartum ketamine infusion using a maximum tolerated dose (MTD) 3+3 design. A loading dose over 1 hour will be the MTD variable to be tested, as our data suggest that ketamine side effects occur with the loading dose. The investigators hypothesize that subanesthetic ketamine dose will be well tolerated and any noted side effects will be rated acceptable by postpartum women following cesarean delivery.

Detailed Description

Pain management for women having a cesarean delivery is rather limited and risks poor pain control, depressed mood, and poor recovery following the cesarean delivery. Current cesarean pain management treatments ignore the multidimensionality of pain, including the influence of mood on pain. Recent evidence suggests that ketamine may provide successful post-surgical pain management, opioid reduction, and rapid reduction of depressive symptoms. The current study aims to identify an appropriate dose of ketamine for post-cesarean pain management while minimizing potential dose-dependent side effects in women following childbirth.

Study Timeline

• Study First Submitted: 2023-06-07
• Study First Submitted QC: 2023-06-07
• Study First Posted: 2023-06-18
• Study Start: 2023-09-25
• Primary Completion: 2024-06-26
• Study Completion: 2024-09-19
• Results First Submitted: 2025-06-26
• Status Verified: 2025-09
• Results First Submitted QC: 2025-09-11
• Last Update Submitted: 2025-09-11
• Results First Posted: 2025-09-12
• Last Update Posted: 2025-09-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 12

Inclusion Criteria

• Adults 18 years and older
• Cesarean Delivery
• American Society of Anesthesiologists Physical Status of 2 or 3
• Neuraxial anesthesia with neuraxial morphine
• Term delivery ≥37 weeks gestation
• Either planning not to breastfeed, OR receiving ketamine as part of routine clinical care

Exclusion Criteria

• General anesthesia
• Allergy to study medications
• ASA PS 4 or higher
• Contraindications to neuraxial anesthesia
• Preterm delivery (<37 weeks gestation)
• Anticipated fetal-neonatal complex care plan
• Participating in another pain intervention trial
• Hypertensive disorder of pregnancy
• Pre-eclampsia with severe features
• Hemodynamic instability
• Medical History exclusions: ketamine or PCP (phencyclidine) abuse, schizophrenia or psychosis, liver or renal insufficiency, uncontrolled hypertension, chest pain, arrhythmia, head trauma, or intracranial hypertension, uncontrolled thyroid disease, or other contraindications to ketamine

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Ketamine (Ketalar) Dose Level 1	Ketamine (Ketalar) Dose Level 1	Ketamine (Ketalar) Dose Level 1: Loading Dose: 0.05 mg/kg/hr X 1 hour; Maintenance Dose 0.05 mg/kg/hr x 12 hours
Ketamine (Ketalar) Dose Level 2	Ketamine (Ketalar) Dose Level 2	Ketamine (Ketalar) Dose Level 2: Loading Dose: 0.08 mg/kg/hr X 1 hour; Maintenance Dose 0.05 mg/kg/hr x 12 hours
Ketamine (Ketalar) Dose Level 3	Ketamine (Ketalar) Dose Level 3	Ketamine (Ketalar) Dose Level 3: Loading Dose: 0.12 mg/kg/hr X 1 hour; Maintenance Dose 0.05 mg/kg/hr x 12 hours
Ketamine (Ketalar) Dose Level 4	Ketamine (Ketalar) Dose Level 4	Ketamine (Ketalar) Dose Level 4: Loading Dose: 0.18 mg/kg/hr X 1 hour; Maintenance Dose 0.05 mg/kg/hr x 12 hours

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose of Ketamine	Between 0 to 24 hours postpartum	Maximum tolerated dose of ketamine is measured by dose that fewer than 33% of patients experience a dose-limiting toxicity (DLT) defined by intolerability. Tolerability will be defined as: lack of adverse events (adverse event defined as: severe unresolved hemodynamic effect: systolic blood pressure \<80 or \>160, heart rate \<40 or \>120). Intolerability will be defined as presence of any adverse event (i.e., severe unresolved hemodynamic effect: systolic blood pressure \<80 or \>160, heart rate \<40 or \>120). Outcome measure of tolerability and intolerability will be reported as n (%). The MTD was 0.18 mg/kg/hr for one hour, followed by 0.05 mg/kg/hr for 11 hours.

Secondary Outcome Measures

Name	Time	Method
Patient Reported Acceptability of Any Reported Side Effects	Between 0 to 24-hours postpartum	Number (%) of patient cohort reporting acceptability at each ketamine dose. Patient reported acceptability was recorded from a 21-question survey that reviewed seven common side effects: dizziness, lightheadedness, bad dreams, hallucinations, nausea, vomiting, and itchiness. Unacceptability is defined as patients reporting any of seven side effects as unacceptable.

Trial Locations

Locations (1)

Magee Womens Hospital of UPMC; 🇺🇸 Pittsburgh, Pennsylvania, United States