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

Ketamine Tolerated Dose for Postpartum Depression and Pain After Cesarean Delivery (PREPARE1)

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.

Study Overview

• Status: Completed
• Conditions: Pain, Postoperative; Depression, Postpartum
• Intervention / Treatment: Drug: Ketamine (Ketalar) Dose Level 1; Drug: Ketamine (Ketalar) Dose Level 2; Drug: Ketamine (Ketalar) Dose Level 3; Drug: Ketamine (Ketalar) Dose Level 4

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 Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Magee Womens Hospital of UPMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: 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; Other Names: 0.05 mg/kg/1hr loading dose Ketamine
Experimental: 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	Drug: 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; Other Names: 0.08 mg/kg/1hr loading dose Ketamine
Experimental: 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	Drug: 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; Other Names: 0.12 mg/kg/1hr loading dose Ketamine
Experimental: 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	Drug: 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; Other Names: 0.18 mg/kg/1hr loading dose Ketamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose of Ketamine	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.	Between 0 to 24 hours postpartum

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Reported Acceptability of Any Reported Side Effects	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.	Between 0 to 24-hours postpartum

Collaborators and Investigators

• Sponsor: Grace Lim, MD, MS
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Grace Lim, MD, MSc, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2023
• Primary Completion (Actual): June 26, 2024
• Study Completion (Actual): September 19, 2024

Study Registration Dates

• First Submitted: June 7, 2023
• First Submitted That Met QC Criteria: June 7, 2023
• First Posted (Actual): June 18, 2023

Study Record Updates

• Last Update Posted (Estimated): September 12, 2025
• Last Update Submitted That Met QC Criteria: September 11, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Cesarean Delivery
• Additional Relevant MeSH Terms: Urogenital Diseases; Pain; Neurologic Manifestations; Mental Disorders; Postoperative Complications; Pathologic Processes; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Mood Disorders; Puerperal Disorders; Depressive Disorder; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative; Depression, Postpartum; Organic Chemicals; Hydrocarbons; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Ketamine
• Other Study ID Numbers: STUDY22100018; R01MH134538 (U.S. NIH Grant/Contract: National Institute of Mental Health)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified data will be available for public benefit and knowledge. Items for uploading will include clinical measures, patient reported outcomes, psychometric testing data, sensory testing data, and all PK data. Technical protocols and any other data collected under this project will be shared upon request to allow others to perform secondary analyses.
• IPD Sharing Time Frame: Beginning with 3 months and ending at 5 years following article publication.
• IPD Sharing Access Criteria: Researchers who propose a methodologically sound proposal may submit said proposals to limkg2@upmc.edu. To gain access to data, requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No