PCORI Comparative Effectiveness Study-Esketamine (Spravato) vs. Ketamine-Equivalence Study

NCT ID: NCT06713616

Last Updated: 2025-05-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

400 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-01-27

Study Completion Date

2030-12-31

Brief Summary

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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.

Detailed Description

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This non-inferiority, multi-site, comparative effectiveness study will utilize a randomized design. Individuals with treatment resistant depression (TRD) will be randomized (1:1) to Spravato® or IV ketamine. This 5-year multisite comparative effectiveness study will enroll 400 total patients (\~200 per group).

Conditions

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Depression

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This study is a randomized phase 3 drug treatment study. Subjects will be randomized, in randomly varying blocks of no more than 8 at each site, to receive either esketamine (Spravato®) or intravenous ketamine. This study is unblinded.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Racemic Ketamine

Ketamine will be given intravenously. Per FDA guidance, the max dose of ketamine will be 60mg per day, with a total lifetime limit of 8 doses. Ketamine will be infused over 40 minutes.

Group Type EXPERIMENTAL

Racemic ketamine

Intervention Type DRUG

Ketamine will be given intravenously. Per FDA guidance, the max dose of ketamine will be 60mg per day, with a total lifetime limit of 8 doses. Ketamine will be infused over 40 minutes.

Spravato (Esketamine)

Spravato® (Esketamine) will be given intranasally. For esketamine, the dose will be between 56 and 84mg, according to the FDA label for the drug. Allowances will be made for patients who have difficulty tolerating these doses to be dosed at 28mg in subsequent treatment sessions.

Group Type EXPERIMENTAL

Spravato (Esketamine)

Intervention Type DRUG

Spravato® (Esketamine) will be given intranasally. For esketamine, the dose will be between 56 and 84mg, according to the FDA label for the drug. Allowances will be made for patients who have difficulty tolerating these doses to be dosed at 28mg in subsequent treatment sessions.

Interventions

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Racemic ketamine

Ketamine will be given intravenously. Per FDA guidance, the max dose of ketamine will be 60mg per day, with a total lifetime limit of 8 doses. Ketamine will be infused over 40 minutes.

Intervention Type DRUG

Spravato (Esketamine)

Spravato® (Esketamine) will be given intranasally. For esketamine, the dose will be between 56 and 84mg, according to the FDA label for the drug. Allowances will be made for patients who have difficulty tolerating these doses to be dosed at 28mg in subsequent treatment sessions.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Provision of signed and dated informed consent form
* Stated willingness to comply with all study procedures and availability for the duration of the study
* Adults ages 18 or older
* Diagnosis of major depressive disorder that is refractory to two or more antidepressant trials
* Moderate or severe depression based on an initial MADRS score ≥ 25
* Judged appropriate for ketamine or esketamine by clinician, independent of potential study participation
* A female participant must be:

a. Not of childbearing potential\*, OR b. Of childbearing potential and practicing a highly effective method of contraception (failure rate of \<1% per year when used consistently and correctly) and agrees to remain on a highly effective method while receiving study intervention and until 1 week after last dose - the end of relevant systemic exposure. The investigator will evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of drug. Acceptable methods of contraception are: i. combined (estrogen and progestogen containing) hormonal or progestogen-only hormonal contraception associated with inhibition of ovulation (oral, transdermal, or intravaginal) ii. intrauterine device (IUD) iii. intrauterine hormone-releasing system (IUS) iv. bilateral tubal occlusion/ligation v. male partner with a bilateral vasectomy with documented aspermia or a bilateral orchiectomy vi. male or female condom with spermicide, diaphragm, or sponge with spermicide (Note: Use of condom as the sole method of contraception is not considered to be a highly effective method of contraception).
* A female participant must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study \* We will consider women to be of childbearing potential if they are within 2 years of menopause (within 3 years since last menstrual period) and have not had a hysterectomy, bilateral oophorectomy, or other definitive surgical intervention.

Exclusion Criteria

* Diagnosis of bipolar disorder or psychotic disorder (i.e., schizophrenia, schizoaffective disorder)
* Other psychiatric comorbidities are permitted so long as depression is the predominant diagnosis
* Active or recent (within 12 months) substance use disorder (other than nicotine)
* Pregnant or lactating women
* Intracerebral hemorrhage or aneurysmal vascular disease
* Hypersensitivity to ketamine, esketamine or any of the excipients
* Known family history of ketamine use disorder
* Prior known ketamine use disorder as well as subjects for whom study participations will result in more than 8 lifetime exposures to ketamine (e.g., prior exposure to ketamine, prior recreational use with ketamine)
* Uncontrolled hypertension, as demonstrated by a blood pressure of greater than 145 / 90 at screening visit. (Pre-treatment blood pressure will be permitted to be 150 / 95 to allow for "whitecoat" hypertension on treatment visits 1-8.)
* Known cardiovascular and cerebrovascular conditions that are associated with an increased risk related to ketamine or esketamine administration (including space-occupying CNS lesions). This includes those prospective participants who undergo EKG and are shown to have an abnormality that would put them at increased risk related to treatment.
* Known condition for which an acute rise in blood pressure would pose a serious risk.
* Arteriovenous malformation
* Positive urine toxicology at screening visit, except for substances that are prescribed (i.e., benzodiazepines, stimulants). Given the extended length of time between exposure and negative toxicology screen, a positive screen for THC will not be exclusionary unless the pattern of use and clinical evaluation are indicative of cannabis use disorder. Cannabis used within 24 hours of dosing is exclusionary.
* Positive alcohol breathalyzer at screening or clinical signs of intoxication
* The patient is unable to arrange for someone to drive them home after each treatment session; patients who are unwilling to refrain from driving and operating machinery on treatment days until the next day following sleep will be excluded.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Patient-Centered Outcomes Research Institute

OTHER

Sponsor Role collaborator

Yale University

OTHER

Sponsor Role lead

Responsible Party

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Samuel Wilkinson

Associate Professor of Psychiatry

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Samuel Wilkinson, MD

Role: PRINCIPAL_INVESTIGATOR

[email protected]

Locations

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Mood Institute

Milford, Connecticut, United States

Site Status RECRUITING

Yale School of Medicine

New Haven, Connecticut, United States

Site Status RECRUITING

Emory University

Atlanta, Georgia, United States

Site Status RECRUITING

University of Michigan

Ann Arbor, Michigan, United States

Site Status RECRUITING

LifeStance Health

Moore, Oklahoma, United States

Site Status RECRUITING

Houston Center for Advanced Psychiatric Treatment

Bellaire, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Cindy Voghell

Role: CONTACT

203-737-4784

Facility Contacts

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Lisa Harding, MD

Role: primary

203-701-9737

Samuel Wilkinson, MD

Role: primary

203-764-9131

Brandon Kitay, MD

Role: primary

404-712-6939

Sagar Parikh, MD

Role: primary

734-232-0011

Rachel Dalthorp, MD

Role: primary

Sandhya Prashad, MD

Role: primary

Sarah Hartigan

Role: backup

(832) 730 - 5196

Other Identifiers

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23-005287

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2000037121

Identifier Type: -

Identifier Source: org_study_id

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