Ketamine to Improve Recovery After Cesarean Delivery - Part 1

NCT ID: NCT04037085

Last Updated: 2022-12-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-09
• Study Completion Date: 2021-08-01

Brief Summary

The objective of this study is evaluate the breastmilk transfer and pharmacokinetics (Part 1) and effectiveness (Part 2) of a post-cesarean delivery intravenous ketamine bolus-and-infusion strategy, as a preventive analgesic modality to reduce pain and opioid requirements.

In Part 1, physiochemical analysis of pharmacokinetic/pharmacodynamic (PK/PD) and breastmilk transfer of ketamine and its metabolites will be assessed. Additionally calculated estimations for neonatal and infant exposure will be assessed.

In Part 2, PK/PD assessments will continue in a larger cohort; endpoints will also include postpartum pain, depression scores, central sensitization measures, patient-reported postpartum recovery scores, breastfeeding, and parent-infant bonding, assessed in the acute post-cesarean period and up to 12 weeks postpartum in a randomized controlled trial.

Detailed Description

Postpartum pain management strategies currently permit opioids for breakthrough pain, but strategies focused on minimizing or eliminating opioids are lacking. In the non-obstetric surgical population, modalities such as intravenous ketamine are well-recognized as effective adjuncts in opioid-reduction strategies for postoperative pain. Although there have been some studies of ketamine exposure in postpartum women without deleterious outcomes noted, these studies in pregnant and lactating women are limited by a lack of information on maternal pharmacokinetics, breastmilk secretion, and clinical effectiveness when used with standard multimodal analgesic approaches. There is also a lack of information on intermediate and long-term outcomes in this setting. This two-part trial will address these knowledge gap by advancing understanding of the safety and efficacy of ketamine and its metabolites in peripartum populations.

Conditions

Obstetric Pain; Postpartum Depression; Breastfeeding; Pain, Acute; Pain, Chronic; Obstetric Anesthesia Problems; Drug Effect; Opioid Use

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Ketamine

Ketamine - IV after cord clamping; IV infusion for 12 hours OR in the weaning population IV Ketamine infusion for 12 hours in the Montefiore CTRC

Group Type: EXPERIMENTAL

Ketamine

Intervention Type: DRUG

Subjects in the intervention arm will receive infusion dosing as noted in arm/group descriptions at the time of cord clamping. Duration of infusion will be 12 hours. Concentrations of ketamine and ketamine metabolites (nor-ketamine, NKET; and dehydro-nor-ketamine, DHNK) are measured in maternal plasma and urine as well as breastmilk. Maternal side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and over 15 hours after infusion discontinuation.

Interventions

Ketamine

Subjects in the intervention arm will receive infusion dosing as noted in arm/group descriptions at the time of cord clamping. Duration of infusion will be 12 hours. Concentrations of ketamine and ketamine metabolites (nor-ketamine, NKET; and dehydro-nor-ketamine, DHNK) are measured in maternal plasma and urine as well as breastmilk. Maternal side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and over 15 hours after infusion discontinuation.

Intervention Type: DRUG

Other Intervention Names

Ketalar

Eligibility Criteria

Inclusion Criteria

• Adult female patients (i.e., ≥18 years of age) and able to provide informed consent
• Cesarean Delivery, Scheduled or Non-Emergent (delivery within 15 minutes not necessary), or female weaning off of breastfeeding
• Cesarean cohort: ASA PS 2 or 3, with or without E designation (delivery within 15 minutes not necessary), Scheduled or Non-Emergent
• Spinal anesthesia with intrathecal morphine if Cesarean Delivery, Scheduled or Non-Emergent
• Multimodal postop analgesia with IV ketorolac, PO NSAID, and PO APAP if Cesarean Delivery, Scheduled or Non-Emergent
• Women who do not plan to breastfeed or who want to temporarily withhold breastfeeding or who are weaning off of breastfeeding (Part 1)

Exclusion Criteria

• Cesarean Delivery under General Anesthesia
• Allergies to study medications
• ASA PS 4 or 4E
• ASA PS with E designation because delivery within 15 minutes required
• ASA PS greater than 4 (moribund patients)
• Contraindications to spinal anesthesia
• Contraindications to NSAIDs (gastric bypass, etc.)
• Contraindication to any other multimodal analgesia medicine
• Adverse occurrence during caesarean section such as hemorrhage, need for transfusion, hemodynamic instability
• Placenta accreta spectrum or previa with large anticipated blood loss
• History of hallucinations, alcohol or illicit substance use/abuse, chronic opioid therapy, or chronic pain (chronic pain - defined by any condition requiring consistent follow up with pain specialist or daily administration of pain medications that could augment sedative effects)
• Pre-eclampsia with severe features

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Pittsburgh

OTHER

Sponsor Role: collaborator

Grace Lim, MD, MS

OTHER

Sponsor Role: lead

Responsible Party

Grace Lim, MD, MS

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Grace Lim, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

UPMC Montefiore Hospital CTRC

Pittsburgh, Pennsylvania, United States

Minhnoi C Wroble Biglan

Pittsburgh, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

STUDY18120046

Identifier Type: -

Identifier Source: org_study_id