VA Aripiprazole vs Esketamine for Treatment... — Clinical Trial Details

Detailed Description

VAST-D II was designed as a multicenter, randomised, open-label, parallel-group study to compare adjunctive intranasal esketamine with adjunctive oral aripiprazole in veterans with unipolar treatment-resistant depression; primary outcome was remission at six weeks assessed by blinded central raters using QIDS-C16.

The trial planned 940 participants across approximately 25 VA medical centres with follow-up visits at weeks 1,2,3,4,6,8,10,12,18 and 24 to assess symptom change, tolerability, attrition, quality of life, and cost-effectiveness; the registry records actual enrolment of 0 and the study was withdrawn.

Study Arms & Interventions

Esketamine

experimental

Adjunctive intranasal esketamine (Spravato) administered per Spravato schedule: twice weekly for first 4 weeks, then once weekly until week 12, with clinician-determined dosing up to 6 months.

Interventions

Esketamine
via Inhalation• Twice weekly (weeks 1–4), then once weekly (weeks 5–12); ongoing per clinician
Intranasal spray; dose per product label/clinician.

Aripiprazole

active comparator

Adjunctive oral aripiprazole per treating clinician

Participants

Ages

18 – 74

Sexes

Male & Female

BMI

Psychosis History

Inclusion Criteria

Inclusion Criteria:
DSM-5 diagnosis of current episode of major depressive disorder (MDE, single or recurrent, non-psychotic) by MINI
TRD defined as at least 2 failed trials of antidepressants (adequate dose and duration) including the current episode and another during last 2 years
Current QIDS-C16 score of > 14
Currently on an antidepressant medication at stable dose for at least 6 weeks without adequate improvement
Ages 18-74 years old at the time of randomization

Exclusion Criteria

Exclusion Criteria:
Lifetime history of bipolar disorder, schizophrenia, schizoaffective disorder, or other psychotic disorder
Presence of psychotic features in the current MDE
Lifetime history of major neurocognitive disorder or any diagnosed neurodegenerative or neurodevelopmental disorder
Current evidence of cognitive dysfunction based on MoCA score < 24
Hypersensitivity to ESK or ketamine
History of aneurysmal vascular disease or arteriovenous malformation
History of intracerebral hemorrhage
Uncontrolled hypertension (systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg, unless cleared by the patient's primary care physician)
History of significant cardiovascular disease, including recent myocardial infarction (within last 12 months), unstable angina, or chronic heart failure
History of interstitial or ulcerative cystitis
Any current unstable medical condition that in the opinion of the investigator would place the patient at increased risk, including hepatic, respiratory, immunological, cardiovascular, endocrine, or renal disease
Imminent need for psychiatric hospitalization
History of moderate or severe SUD in last 6 months will be excluded, not including cannabis, tobacco, and caffeine
Women who are pregnant, lactating, or planning to become pregnant or those of childbearing potential who are sexually active but unwilling to use a contraceptive
Unable to provide informed consent
Current treatment with any antipsychotic
Prior antidepressant treatment with ketamine or ESK within the current episode/past two years
Prior antidepressant treatment with ARI at an FDA-approved dose for at least 6 weeks within the past 2 years
Lifetime history of ketamine use disorder
History of drug induced leukopenia

Company

Product

Legal

VA Aripiprazole vs Esketamine for Treatment Resistant Depression (VAST-D II)

Detailed Description

Study Arms & Interventions

Esketamine

Interventions

Aripiprazole

Locations

Interventions

Participants

Inclusion Criteria

Exclusion Criteria

Study Details

Study Team

Sponsors & Collaborators