- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04227704
Ketamine to Prevent PPD After Cesarean (PoCKet)
Postpartum Depression After Cesarean Delivery: Ketamine as a Preventative Intervention: A Feasibility Pilot-study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Postpartum depression (PPD)
PPD is one of the most common perinatal medical complications and can have a detrimental effect on both mother and baby. Suicide exceeds hemorrhage and hypertensive disorders as a cause of maternal mortality and maternal psychopathology interferes with the parent-infant relationship. It has been estimated to have a period prevalence of 19.2% in the first 3 postpartum months. The rapid decline in reproductive hormones is thought to contribute to the development of PPD in susceptible women, although the specific pathogenesis is unknown. The American College of Obstetricians and Gynecologists recommend that all women should be routinely screened for depressive symptoms in the perinatal period.
Risk factors for PPD include:
- Depression during pregnancy • Breastfeeding problems
- Preterm birth/infant admission to neonatal intensive care (NICU)
- Traumatic birth experience
- History of depression
- Anxiety during pregnancy
Ketamine's anti-depressant effect
Ketamine, a phencyclidine derivative, is a non-competitive antagonist at the N-methyl-D-aspartic acid (NMDA) receptor that is commonly used as an anesthetic or sedative agent and has proven analgesic effect after a variety of surgeries including CD, where it has also been shown to reduce shivering. It has been demonstrated to have a rapid anti-depressant effect in treatment-resistant depression outside of pregnancy. The most commonly employed intravenous (IV) dose for this purpose is 0.5 mg/kg over 40 minutes, as single or repeated infusions. It has been postulated that prolonged blockade of NMDA receptors causes long-term changes in signal transduction leading to sustained clinical improvement, some investigators have explored longer term infusions such as those used to treat chronic pain. A recent pilot study assessing the feasibility of a 96-hour (~0.5mg/kg/hr) infusion compared with a single 40-minute (0.5 mg/kg) infusion suggested a trend toward greater efficacy in the prolonged infusion but confirmation of a statistically significant result is awaited.
Ketamine and PPD
This promising anti-depressant effect has prompted investigation of ketamine as a preventative measure in patients undergoing CD. There have been 2 studies to date, one which failed to demonstrate any benefit from a bolus dose of 0.25 mg/kg and one which documented a large reduction (1 and 22% in the treatment and control, respectively) in the (6 week) period prevalence of postpartum depression after a 4 mg/kg dose of ketamine over 50 hours (~0.08 mg/kg/hr).
The prolonged IV infusion, was achieved by adding the ketamine to a sufentanil patient-controlled analgesic (PCA) pump with a background infusion. This PCA pump is a standard part of their post-cesarean analgesic regimen. In our institution, it is standard practice to discontinue IV infusions and to remove IV cannulae as early as it is safe to do so. This practice is essential to the attempts to enhance postoperative recovery and aid mother's bonding with their babies and facilitate their early-life care. This reflects patients' expectations and preferences and is in line with other maternity units across North America and Europe.
The natural course of PPD varies and, although it may resolve spontaneously within weeks, approximately 20% of women with PPD still have depression at 12 months and beyond. As many as 13% will still have depressive symptoms at 2 years and 40% will have a relapse. Considering the maternal suffering, disruption to the family, potential impairment of the social, emotional, and cognitive development of the child, and the rare cases of infanticide and suicide caused by PPD, the impact on families and society as a whole is difficult to overemphasize. An intervention that promises such a large reduction in this devastating disease warrants extensive research. In an attempt to achieve the benefit whilst employing methods more acceptable to our patients we have designed a pilot study to assess the feasibility of our study design and collect preliminary tolerability and efficacy data on ketamine administered by two alternative routes: 40-minute IV infusion (i.v.) and subcutaneous (s.c.) injection.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University in St. Louis
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion criteria:
- Term pregnancy
- Age 18-45 years of age
- Scheduled cesarean delivery under neuraxial anesthesia
Exclusion criteria:
- ASA classification IV or V
- History of psychotic episodes
- History of allergy to ketamine
- Inability to communicate in English or any other barrier to providing informed consent
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Control
Shortly after cesarean delivery of their baby, participants will receive a subcutaneous injection and 40-minute intravenous infusion of 0.9% sodium chloride.
|
Administration of 0.9% Sodium Chloride (N/S)
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Experimental: Ketamine SC
Shortly after cesarean delivery of their baby, participants will receive a subcutaneous injection of 0.5 mg/kg of ketamine and a 40-minute intravenous infusion of 0.9% sodium chloride.
|
Administration of 0.9% Sodium Chloride (N/S)
Administration of a 0.5 mg/kg dose of ketamine at cesarean delivery by one of two routes (subcutaneous or 40-minute IV infusion).
|
Experimental: Ketamine IVI
Shortly after cesarean delivery of their baby, participants will receive a subcutaneous injection of 0.9% sodium chloride and a 40-minute intravenous infusion of 0.5 mg/kg ketamine.
|
Administration of 0.9% Sodium Chloride (N/S)
Administration of a 0.5 mg/kg dose of ketamine at cesarean delivery by one of two routes (subcutaneous or 40-minute IV infusion).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The Prevalence of Postpartum Depression in the Study Population, as Defined as EPDS Greater Than 10 Out of 30
Time Frame: 42 days postpartum
|
Establish a sufficient burden of disease (>10%) in our population to warrant a full RCT
|
42 days postpartum
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Percentage of Eligible Patients Consenting to Participation
Time Frame: Through study completion, approximately 9 months
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Establish a recruitment rate of greater than 50% to confirm the feasibility of conducting an RCT in our population Twenty-five (20.7%) out of 121 women who were approached consented to participation. 2 were withdrawn with 23 completing participation. |
Through study completion, approximately 9 months
|
Percentage of Patients With a Complete Dataset
Time Frame: Through study completion, approximately 9 months
|
Ensure that the design of assessments and data collection make it possible to achieve a complete dataset in >90% of participants
|
Through study completion, approximately 9 months
|
Number of Patients in Study Arms Experiencing One or More Severe Side Effects
Time Frame: Through study completion, approximately 9 months
|
Ascertain that neither of the chosen routes of administration of ketamine are intolerable to patients, as defined as the incidence of one or more severe side effects experienced by >10% of participants in that study arm.
|
Through study completion, approximately 9 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Admission to NICU
Time Frame: Postpartum day 1
|
Incidence of admission
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Postpartum day 1
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Dose of Opiate Analgesics Administered
Time Frame: Intraoperative phase, approximately 2 hours
|
Intraoperative supplementary analgesia in morphine milligram equivalents
|
Intraoperative phase, approximately 2 hours
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Dose of Ketorolac Administered (mg)
Time Frame: Intraoperative phase, approximately 2 hours
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Intraoperative supplementary analgesia
|
Intraoperative phase, approximately 2 hours
|
Prevalence of Intraoperative Hypotension
Time Frame: Intraoperative phase, approximately 2 hours
|
Prevalence of participants with intraoperative hypotension of a systolic BP of less than 90
|
Intraoperative phase, approximately 2 hours
|
Maximum Intraoperative Pain (NRS)
Time Frame: Intraoperative phase, approximately 2 hours
|
Reported maximal level of intraoperative pain on the numerical rating scale 0 - 10, where 0 is no pain and 10 is the worst pain imaginable
|
Intraoperative phase, approximately 2 hours
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Adverse Effects
Time Frame: Intraoperative and 2 and 6 hours postoperatively
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Incidence and severity (mild, moderate or severe) of nausea, vomiting, pruritus, dizziness, sedation, shivering, anxiety, euphoria, hallucinations, amnesia, blurred vision, diplopia, nystagmus
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Intraoperative and 2 and 6 hours postoperatively
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Plasma Concentrations of Ketamine
Time Frame: At baseline and approximately 20, 40 and 100 minutes postpartum
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Assays of venous blood samples
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At baseline and approximately 20, 40 and 100 minutes postpartum
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Total Opiate Consumption in Morphine Equivalents
Time Frame: In the first 2 days postpartum
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Morphine equivalents
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In the first 2 days postpartum
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Surgical Site Pain: Numerical Rating Scale (NRS 0-10)
Time Frame: At 2, 6, 24 and 48 hours after delivery and on postpartum days 21 and 42
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Surgical site pain on a numerical rating scale of 0-10, where 0 is no pain and 10 is the worst pain imaginable.
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At 2, 6, 24 and 48 hours after delivery and on postpartum days 21 and 42
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Edinburgh Postpartum Depression Scale (EPDS)
Time Frame: On postpartum days 1, 2, 21 and 42
|
The EPDS is a validated measure of depressive symptoms in the postpartum period.
The scale is scored between 0 - 30, a higher score represents greater depressive symptomatology.
We report the study mean of each participant's mean EPDS score for their postpartum assessments
|
On postpartum days 1, 2, 21 and 42
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Apgar Scores
Time Frame: At 1 and 5 minutes after delivery
|
Apgar score (0-10) comprised of an assessment of neonatal color, tone and crying.
A higher score indicates healthier color, tone and crying.
|
At 1 and 5 minutes after delivery
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The Number of Participants Achieving Breastfeeding Success
Time Frame: Postpartum days 1 and 2
|
An indication of whether breastfeeding has been successfully established (Yes or No).
|
Postpartum days 1 and 2
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Prevalence of Intraoperative Hypertension
Time Frame: Intraoperative phase, approximately 2 hours
|
Prevalence of intraoperative hypertension as defined by number of participants with a systolic blood pressure greater than 140 mmHg
|
Intraoperative phase, approximately 2 hours
|
Prevalence of Intraoperative Bradycardia
Time Frame: Intraoperative phase, approximately 2 hours
|
Prevalence of intraoperative bradycardia, defined as number of participants with a heart rate of less than 40 bpm
|
Intraoperative phase, approximately 2 hours
|
Prevalence of Intraoperative Tachycardia
Time Frame: Intraoperative phase, approximately 2 hours
|
Prevalence of intraoperative tachycardia as defined by the number of participants with a heart rate greater than 110 bpm
|
Intraoperative phase, approximately 2 hours
|
Postpartum Anxiety
Time Frame: On day of surgery, and postpartum days 1, 2, 21 and 42
|
Mean Anxiety in the postpartum.
General Anxiety Disorder 7-item Scale (GAD-7), ranges from 0 to 21.
Higher scores indicate more severe anxiety.
|
On day of surgery, and postpartum days 1, 2, 21 and 42
|
Collaborators and Investigators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Behavioral Symptoms
- Mental Disorders
- Mood Disorders
- Pregnancy Complications
- Puerperal Disorders
- Depressive Disorder
- Depression
- Depression, Postpartum
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Anesthetics, Dissociative
- Anesthetics, Intravenous
- Anesthetics, General
- Anesthetics
- Excitatory Amino Acid Antagonists
- Excitatory Amino Acid Agents
- Ketamine
Other Study ID Numbers
- 201910191
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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