Actively Recruiting
PCORI Comparative Effectiveness Study-Esketamine (Spravato) vs. Ketamine-Equivalence Study
Led by Yale University · Updated on 2026-05-05
400
Participants Needed
6
Research Sites
309 weeks
Total Duration
On this page
Sponsors
Y
Yale University
Lead Sponsor
P
Patient-Centered Outcomes Research Institute
Collaborating Sponsor
AI-Summary
What this Trial Is About
The purpose of this study is to compare the relative effectiveness, acceptability, and side effects of ketamine delivered through an IV (a drip into the arm) which is not currently FDA approved for use in the treatment of treatment-resistant depression (TRD) and Esketamine (Spravato®), taken as a nasal spray which has received FDA approval for use in the treatment of treatment-resistant depression (TRD) in the treatment of patients with treatment-resistant depression (TRD). The study will look at the following: * How well the treatment helps with symptoms of depression (effectiveness), * How comfortable and willing people are to use the treatment (acceptability), and * How well people can deal with any side effects from the treatment (tolerability). The study will also examine factors that may predict which treatment works better for certain patients.
CONDITIONS
Official Title
PCORI Comparative Effectiveness Study-Esketamine (Spravato) vs. Ketamine-Equivalence Study
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Signed and dated informed consent form provided
- Willingness to comply with all study procedures and available for the study duration
- Adults aged 18 years or older
- Diagnosed with major depressive disorder resistant to two or more antidepressant trials
- Moderate or severe depression with an initial MADRS score of 25 or higher
- Clinician judgment that ketamine or esketamine treatment is appropriate
- Female participants must either not be of childbearing potential or use a highly effective contraception method and agree to continue it during treatment and for 1 week after last dose
- Female participants must agree not to donate eggs or freeze them for assisted reproduction during the study
- Women considered of childbearing potential are within 2 years of menopause and have not had certain surgical procedures like hysterectomy or bilateral oophorectomy
You will not qualify if you...
- Diagnosis of bipolar disorder or psychotic disorders (e.g., schizophrenia, schizoaffective disorder)
- Active or recent substance use disorder within 12 months, except nicotine
- Pregnant or lactating women
- Intracerebral hemorrhage or aneurysmal vascular disease
- Hypersensitivity to ketamine, esketamine, or any ingredients
- Known personal or family history of ketamine use disorder
- Prior ketamine use disorder or more than 8 lifetime ketamine exposures
- Prior esketamine exposure
- Uncontrolled hypertension (blood pressure over 145/90 at screening)
- Cardiovascular or cerebrovascular conditions increasing risk with ketamine or esketamine
- Conditions where acute blood pressure rise is dangerous
- Arteriovenous malformation
- Positive urine toxicology at screening except prescribed substances; recent cannabis use within 24 hours is exclusionary
- Positive alcohol breath test or signs of intoxication at screening
- Unable or unwilling to have someone drive home after treatment or refrain from driving until next day
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 6 locations
1
Mood Institute
Milford, Connecticut, United States, 06461
Actively Recruiting
2
Yale School of Medicine
New Haven, Connecticut, United States, 06512
Actively Recruiting
3
Emory University
Atlanta, Georgia, United States, 30322
Actively Recruiting
4
University of Michigan
Ann Arbor, Michigan, United States, 48104
Active, Not Recruiting
5
LifeStance Health
Moore, Oklahoma, United States, 73160
Actively Recruiting
6
Houston Center for Advanced Psychiatric Treatment
Bellaire, Texas, United States, 77401
Actively Recruiting
Research Team
C
Cindy Voghell
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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