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Ketamine to Improve Recovery After Cesarean Delivery - Part 1 (KINETIC)

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ClinicalTrials.gov Identifier: NCT04037085
Recruitment Status : Recruiting
First Posted : July 30, 2019
Last Update Posted : September 30, 2019
Sponsor:
Collaborator:
University of Pittsburgh
Information provided by (Responsible Party):
Grace Lim, MD, MS, University of Pittsburgh

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. Physiochemical, PK/PD, and breastmilk transfer of ketamine and its metabolites, as well as calculated estimations for neonatal exposure will be assessed in Part 1. 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.

Condition or disease Intervention/treatment Phase
Obstetric Pain Postpartum Depression Breastfeeding Pain, Acute Pain, Chronic Obstetric Anesthesia Problems Drug Effect Opioid Use Drug: Ketamine Phase 2

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 perinatal populations.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Prospective observational open-label trial (Part 1)
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Evaluation of PK/PD, Breastmillk Transfer, and Effectiveness of Ketamine After Cesarean Delivery - Part 1
Estimated Study Start Date : October 2019
Estimated Primary Completion Date : January 1, 2021
Estimated Study Completion Date : January 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cesarean Section
Drug Information available for: Ketamine

Arm Intervention/treatment
Experimental: Ketamine
Ketamine - IV bolus just after cord clamping, followed by IV infusion for 12 hours
Drug: Ketamine
Subjects in the intervention arm will receive bolus and infusion dosing as noted in arm/group descriptions at the time of cord clamping. Duration of infusion will be 12 hours. Breastmilk, maternal serum and urine, side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and over 15 hours after infusion discontinuation.
Other Name: Ketalar




Primary Outcome Measures :
  1. ketamine (AUC) [ Time Frame: 27 hours postpartum ]
    Breast milk, colostrum, plasma will be used to calculate plasma milk area under the curve (AUC)

  2. ketamine (M:P) [ Time Frame: 27 hours postpartum ]
    M:P ratio will be calculated from milk and plasma levels

  3. ketamine (AID) [ Time Frame: 27 hours postpartum ]
    Absolute infant dose will be calculated from breastmilk

  4. S-ketamine [ Time Frame: 27 hours postpartum ]
    Maternal urine, serum, and breast milk will be used to measure concentrations of ketamine metabolites in these substances

  5. norketamine [ Time Frame: 27 hours postpartum ]
    Maternal urine, serum, and breast milk will be used to measure concentrations of ketamine metabolites in these substances

  6. hydroxyl-ketamine [ Time Frame: 27 hours postpartum ]
    Maternal urine, serum, and breast milk will be used to measure concentrations of ketamine metabolites in these substances

  7. hydroxynorketamine [ Time Frame: 27 hours postpartum ]
    Maternal urine, serum, and breast milk will be used to measure concentrations of ketamine metabolites in these substances

  8. Steady state (Css) [ Time Frame: 27 hours postpartum ]
    Postpartum maternal urine, serum will be used to calculate postpartum maternal ketamine steady state (Css)

  9. Half life (T1/2) [ Time Frame: 27 hours postpartum ]
    Postpartum maternal urine, serum will be used to calculate postpartum maternal ketamine half-life (T1/2)

  10. Volume of distribution [ Time Frame: 27 hours postpartum ]
    Postpartum maternal urine, serum will be used to calculate postpartum maternal ketamine volume of distribution (VD)


Secondary Outcome Measures :
  1. Milligram morphine equivalents (MME) [ Time Frame: 72 hours postpartum ]
    MME consumed in the first 72 hours postpartum

  2. Static, dynamic, and affective VAS pain score [ Time Frame: 72 hours ]
    Pain ratings at rest and with movement and affective pain on a 100mm line

  3. Dynamic acute pain [ Time Frame: 72 hours postpartum ]
    Pain ratings with movement on a 0-100mm line, visual analog scale where 0 is no pain and 100 is the most pain imaginable.

  4. Vital Signs - blood pressure [ Time Frame: 27 hours postpartum ]
    blood pressure will be reported

  5. Vital Signs - heart rate [ Time Frame: 27 hours postpartum ]
    heart rate will be reported

  6. Vital Signs - oxygen saturation [ Time Frame: 27 hours postpartum ]
    oxygen saturation will be reported

  7. Vital Signs - respiratory rate [ Time Frame: 27 hours postpartum ]
    respiratory rate will be reported

  8. Sedation [ Time Frame: 27 hours postpartum ]
    Richmond agitation sedation scale (RASS) scale. -3 or less is moderate to unarousable sedation. -2 to 0 is calm to light sedation. +1 to +4 is restless to combative.

  9. Side effects [ Time Frame: 27 hours postpartum ]
    LSD scale, dizziness, lightheadedness, bad dreams, nausea, vomiting, pruritus, hallucinations



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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)
  • Primary or repeat cesarean delivery
  • >/=37 weeks gestation
  • ASA PS 2 or 3, with or without E designation (delivery within 15 minutes not necessary)
  • Spinal anesthesia with intrathecal morphine
  • Multimodal postop analgesia with IV ketorolac, PO NSAID, and PO APAP
  • Women who do not plan to breastfeed or are temporarily withholding 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
  • Significant psychiatric history, uncontrolled hyperthyroidism, cardiac disease, fever, hypertension
  • Adverse occurrence during caesarean section such as hemorrhage, need for transfusion, hemodynamic instability
  • Placenta accreta or previa with large anticipated blood loss
  • History of hallucinations, alcohol or illicit substance use/abuse, chronic opioid therapy, or chronic pain
  • Pre-eclampsia with severe features

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04037085


Contacts
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Contact: Kelsea LaSorda 412-641-2179 lasordakr@upmc.edu
Contact: Amy Monroe 412-623-6382 monroeal@upmc.edu

Locations
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United States, Pennsylvania
UPMC Magee Womens Hospital Recruiting
Pittsburgh, Pennsylvania, United States, 15215
Contact: Kelsea LaSorda, MPH    412-641-2179    lasordakr@upmc.edu   
Sponsors and Collaborators
Grace Lim, MD, MS
University of Pittsburgh
Investigators
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Principal Investigator: Grace Lim, MD, MS University of Pittsburgh

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Responsible Party: Grace Lim, MD, MS, Principal Investigator, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT04037085     History of Changes
Other Study ID Numbers: STUDY18120046
First Posted: July 30, 2019    Key Record Dates
Last Update Posted: September 30, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Depression, Postpartum
Acute Pain
Chronic Pain
Labor Pain
Puerperal Disorders
Pregnancy Complications
Depressive Disorder
Mood Disorders
Mental Disorders
Pain
Neurologic Manifestations
Signs and Symptoms
Ketamine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action