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

NCT05907213 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: STUDY22100018R01MH134538
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Pain, Postoperative; Depression, Postpartum

Keywords

Cesarean Delivery

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Patient Reported Acceptability of Any Reported Side Effects

  Between 0 to 24-hours postpartum

Study Arms (4)

Ketamine (Ketalar) Dose Level 1

EXPERIMENTAL

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

Ketamine (Ketalar) Dose Level 2

EXPERIMENTAL

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

Ketamine (Ketalar) Dose Level 3

EXPERIMENTAL

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

Ketamine (Ketalar) Dose Level 4

EXPERIMENTAL

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

Interventions

Ketamine (Ketalar) Dose Level 1 DRUG

Loading Dose: 0.05 mg/kg/hr X 1 hour; Maintenance Dose 0.05 mg/kg/hr x 12 hours

Also known as: 0.05 mg/kg/1hr loading dose Ketamine

Ketamine (Ketalar) Dose Level 1

Ketamine (Ketalar) Dose Level 2 DRUG

Loading Dose: 0.08 mg/kg/hr X 1 hour; Maintenance Dose 0.05 mg/kg/hr x 12 hours

Also known as: 0.08 mg/kg/1hr loading dose Ketamine

Ketamine (Ketalar) Dose Level 2

Ketamine (Ketalar) Dose Level 3 DRUG

Loading Dose: 0.12 mg/kg/hr X 1 hour; Maintenance Dose 0.05 mg/kg/hr x 12 hours

Also known as: 0.12 mg/kg/1hr loading dose Ketamine

Ketamine (Ketalar) Dose Level 3

Ketamine (Ketalar) Dose Level 4 DRUG

Loading Dose: 0.18 mg/kg/hr X 1 hour; Maintenance Dose 0.05 mg/kg/hr x 12 hours

Also known as: 0.18 mg/kg/1hr loading dose Ketamine

Ketamine (Ketalar) Dose Level 4

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Grace Lim, MD, MS: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Magee Womens Hospital of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Pain, Postoperative; Depression, Postpartum

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Puerperal Disorders; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Dr. Katherine Grace Lim, Chief of the Division of OB & Women's Anesthesiology
• Organization: University of Pittsburgh, UPMC Department of Anesthesiology & Perioperative Medicine

limkg2@upmc.edu

412-641-1778

Study Officials

• Grace Lim, MD, MSc

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor, Chief Obstetric & Women's Anesthesiology

Model Details: MTD 3+3 design

Study Record Dates

• First Submitted: June 7, 2023
• First Posted: June 18, 2023
• Study Start: September 25, 2023
• Primary Completion: June 26, 2024
• Study Completion: September 19, 2024
• Last Updated: September 12, 2025
• Results First Posted: September 12, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: Beginning with 3 months and ending at 5 years following article publication.
• 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.

Locations

US (1)