NCT06713616 PCORI Comparative Effectiveness Study-Esketamine (Spravato) vs. Ketamine-Equivalence Study
| NCT ID | NCT06713616 |
| Status | Recruiting |
| Phase | Phase 3 |
| Sponsor | Yale University |
| Condition | Depression |
| Study Type | INTERVENTIONAL |
| Enrollment | 400 participants |
| Start Date | 2025-01-27 |
| Primary Completion | 2030-12-31 |
Eligibility & Interventions
Eligibility Fast-Check
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What to Expect as a Participant
You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.
Phase 3 trials are large pivotal studies comparing the treatment to current standard of care or placebo. Your participation directly contributes to the evidence needed for regulatory approval.
This trial targets 400 participants in total. It began in 2025-01-27 with a primary completion date of 2030-12-31.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
Brief Summary
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.
Eligibility Criteria
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). Prior esketamine exposure is also exclusionary. * 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.
Contact & Investigator
Samuel Wilkinson, MD
PRINCIPAL INVESTIGATOR
Samuel.Wilkinson@yale.edu
Frequently Asked Questions
Who can join the NCT06713616 clinical trial?
This trial is open to participants of all sexes, aged 18 Years or older, studying Depression. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
What phase is the NCT06713616 trial and what does that mean for participants?
Phase 3 trials are large-scale studies comparing the new treatment to existing standards of care or a placebo. They provide the evidence needed for regulatory approval. This trial targets 400 participants.
Is NCT06713616 currently recruiting?
Yes, NCT06713616 is actively recruiting participants. Contact the research team at Cynthia.Voghell@yale.edu for enrollment information.
Where is the NCT06713616 trial being conducted?
This trial is being conducted at Milford, United States, New Haven, United States, Atlanta, United States, Ann Arbor, United States and 2 additional locations.
Who is sponsoring the NCT06713616 clinical trial?
NCT06713616 is sponsored by Yale University. The principal investigator is Samuel Wilkinson, MD at Samuel.Wilkinson@yale.edu. The trial plans to enroll 400 participants.
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