Daridorexant for Post-Cardiotomy Delirium Prevention (NCT07217912)
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Overview
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Daridorexant_for_Post_Cardioto["Daridorexant for Post-Cardiotomy Delirium Preven"] -->|"references"| HCRTR2["HCRTR2"]
Daridorexant_for_Post_Cardioto["Daridorexant for Post-Cardiotomy Delirium Preven"] -->|"references"| HCRTR1["HCRTR1"]
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NCT07217912 is a Phase 2 clinical trial conducted by the University of Rochester testing Daridorexant, a dual orexin receptor antagonist (DORA), to prevent delirium following heart surgery (post-cardiotomy delirium). This trial leverages the growing evidence that orexin receptor antagonism may have neuroprotective effects beyond just promoting sleep["@orexin_ad"][@orexin_alzheimers].
Trial Information
| Attribute | Details | |-----------|---------| | NCT Number | NCT07217912 | | Sponsor | University of Rochester | | Principal Investigator | Mark Oldham, MD (Associate Professor of Psychiatry) | | Intervention | Daridorexant 50 mg (or 25 mg with moderate CYP3A4 inhibitor) orally for first 3 nights post-surgery | | Comparator | Matching placebo | | Phase | Phase 2 | | Indication | Post-cardiotomy delirium prevention | | Status | Recruiting | | Enrollment | 80 participants | | Start Date | October 14, 2025 | | Primary Completion | November 1, 2027 (estimated) | | Location | Strong Memorial Hospital, Rochester, New York |
Background
Post-Cardiotomy Delirium
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Overview
Mermaid diagram (expand to render)
NCT07217912 is a Phase 2 clinical trial conducted by the University of Rochester testing Daridorexant, a dual orexin receptor antagonist (DORA), to prevent delirium following heart surgery (post-cardiotomy delirium). This trial leverages the growing evidence that orexin receptor antagonism may have neuroprotective effects beyond just promoting sleep["@orexin_ad"][@orexin_alzheimers].
Trial Information
| Attribute | Details | |-----------|---------| | NCT Number | NCT07217912 | | Sponsor | University of Rochester | | Principal Investigator | Mark Oldham, MD (Associate Professor of Psychiatry) | | Intervention | Daridorexant 50 mg (or 25 mg with moderate CYP3A4 inhibitor) orally for first 3 nights post-surgery | | Comparator | Matching placebo | | Phase | Phase 2 | | Indication | Post-cardiotomy delirium prevention | | Status | Recruiting | | Enrollment | 80 participants | | Start Date | October 14, 2025 | | Primary Completion | November 1, 2027 (estimated) | | Location | Strong Memorial Hospital, Rochester, New York |
Background
Post-Cardiotomy Delirium
Postoperative delirium is a common complication following cardiac surgery, affecting up to 50% of elderly patients. It is characterized by:
Acute onset of confusion and attention deficits
Fluctuating course during the first 3-5 days post-surgery
Potential for long-term cognitive sequelae
Post-cardiotomy delirium is associated with:
Increased mortality risk
Longer hospital stays
Higher rates of institutionalization
Accelerated cognitive decline, particularly in vulnerable patients[@delirium_neuro]
Orexin System and Neurodegeneration
The orexin system (also known as hypocretin system) consists of orexin-A and orexin-B neuropeptides produced in the [lateral hypothalamus](/cell-types/lateral-hypothalamus-orexin-neurons). These neuropeptides regulate:
Sleep-wake cycles
Arousal and alertness
Energy homeostasis
Research has demonstrated connections between orexin signaling and neurodegenerative processes:
Amyloid-beta production: Orexin promotes amyloid-beta production through gamma-secretase modulation, suggesting orexin inhibition may reduce amyloid burden[@orexin_ad]
Tau pathology: Orexin signaling may influence tau phosphorylation and spread
Sleep-dependent clearance: Improved sleep quality enhances glymphatic clearance of toxic proteins including amyloid-beta and tau[@sleep_clarity]
Neuroinflammation: Orexin may modulate inflammatory responses in the brain
Rationale for Daridorexant in Delirium Prevention
The theoretical rationale for using Daridorexant to prevent post-cardiotomy delirium includes:
Sleep restoration: Cardiac surgery disrupts sleep architecture; orexin antagonism can improve sleep quality during the critical early recovery period
Reduced neuronal excitability: Orexin receptor antagonism may reduce the hyperarousal state that contributes to delirium
Neuroprotection: As demonstrated in AD models, orexin antagonism may reduce excitotoxic damage and neuroinflammation
Circadian rhythm stabilization: Orexin plays a key role in circadian regulation; antagonism may help normalize sleep-wake cycles after surgery
Mechanism of Action
Dual Orexin Receptor Antagonism
Daridorexant works by blocking both orexin receptor types:
While this trial targets post-cardiotomy delirium rather than Alzheimer's disease directly, it has significant implications for neurodegeneration research:
Connections to AD
Shared pathways: Postoperative delirium and AD share common mechanisms including neuroinflammation, sleep disruption, and cholinergic dysfunction
Biomarker overlap: Patients who develop postoperative delirium show elevated tau and amyloid biomarkers similar to AD patients
Long-term cognitive trajectories: Delirium may unmask or accelerate underlying AD pathology
Broader Implications
This trial represents a novel therapeutic approach combining: