Mitigating Delirium With Fluvoxamine Treatment for Non-Cardiac Surgery (MD FluNCS)

The Washington University

Status and phase: Not yet enrolling; Phase 3

Conditions: Surgery-Complications; Delirium

Treatments: Drug: Placebo; Drug: Fluvoxamine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06969287

R21AG086855 (U.S. NIH Grant/Contract)

202411151

Details and patient eligibility

About

The investigation will establish biological plausibility and infrastructure required for a multisite clinical trial evaluating the re-purposing of fluvoxamine to mitigate postoperative delirium risk in geriatric patients undergoing non-cardiac non-intracranial surgery.

Full description

Delirium is a disturbance in attention, cognition, and consciousness, an acute physiological consequence of medical events, such as hospital admission, surgery, sepsis, and pharmacological intervention. There are currently no standard pharmacologic interventions to prevent delirium in any setting. The investigation will lay the groundwork for a larger-scale Phase 3 trial geared toward advancing long-term goal of improving public health and quality of life for those at risk of postoperative delirium and related sequelae.

The study assumes that neuroinflammation is a key contributor to the pathogenesis of postoperative delirium, a matter of conjecture. The investigators will directly test systemic inflammation as a proxy for neuroinflammation. The investigation will test whether fluvoxamine may be associated with reduced systemic inflammation, markers of neural dysfunction, and delirium severity.

This potential therapeutic approach has potential generalizability to different clinical settings and already proved useful for COVID-19. The investigators combine the need to develop a collaborative clinical trials platform across diverse healthcare settings with key mechanistic studies that will advance our understanding of the pathogenesis of delirium. These studies will leverage high-density EEG recordings and state-of-the-art plasma biomarker collection, providing key data on the biological plausibility for a fluvoxamine effect.

Enrollment: 46 estimated patients

Sex: All

Ages: 60+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• English-speaking
• elective non-cardiac or non-intracranial surgery requiring at least a 2-day hospital length of stay

Exclusion criteria

• Received investigational drug within the last 7 weeks
• lack of capacity to provide informed consent
• prior known intolerance or allergy to SSRIs or fluvoxamine
• planned postoperative ventilation
• drug or alcohol dependence
• preoperative use of non-NSAID medications with drug-drug interactions of Class X (Avoid Combination) or D (Consider Therapy Modification)
• risk of serotonin syndrome (St John's Wort, SSRIs, or TCA)

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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46 participants in 2 patient groups, including a placebo group

Fluvoxamine

Experimental group

Description:

100 mg of fluvoxamine on the morning of surgery (POD 0), 100 mg on the evening of surgery (POD 0), 100 mg on the morning of POD 1, and 100 mg on the evening of POD 1. All administered as PO capsules.

Treatment:

Drug: Fluvoxamine

Placebo

Placebo Comparator group

Description:

Placebo capsule on the morning of surgery (POD 0), Placebo capsule on the evening of surgery (POD 0), Placebo capsule on the morning of POD 1, and Placebo capsule on the evening of POD 1. All administered PO.

Treatment:

Drug: Placebo