NCT06713616

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

Comparative Effectiveness of Racemic Ketamine Versus Esketamine (Spravato®) for Depression

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 400 (estimated)
• Sponsor: Yale University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

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

• Depression

Interventions

Type	Name	Description
DRUG	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.
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.

Timeline

• Start date: 2025-01-27
• Primary completion: 2030-12-31
• Completion: 2030-12-31
• First posted: 2024-12-03
• Last updated: 2026-02-17

Locations

6 sites across 1 country: United States

Regulatory

• FDA-regulated drug study