Cardiovascular Effects of COVID-19

Study Overview
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Brief Summary
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Cardiometabolic disease may confer increased risk of adverse outcomes in COVID-19 patients by activation of the aldose reductase pathway, a trigger of the inflammatory cascade. The study team hypothesizes that aldose reductase inhibition with AT-001 (caficrestat) might represent a novel therapeutic approach to reduce inflammation and risk of adverse outcomes in diabetic patients with COVID-19. An open-label pilot study to assess safety, tolerability and efficacy of AT-001 in hospitalized COVID-19 patients with history of diabetes mellitus and heart disease will be conducted. Eligible participants will be treated with AT-001 1500 mg twice daily for up to 14 days. Safety, tolerability, survival and length of hospital stay data were compared with matched controls from a contemporaneous registry of COVID-19 patients.

Official Title
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A Single-center Registry and Embedded Interventional Study of the Effects of COVID-19 With and Without Treatment With AT-001 on Cardiac Structure and Function in Patients Hospitalized for Management of COVID-19 Infection

Conditions
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COVID-19

Intervention / Treatment
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* Drug: AT-001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Registry Study: In order to be eligible to participate in the registry study, an individual must meet all of the following criteria: Age ≥18 years of age Hospitalized at one of the participating NYULH locations Confirmed COVID-19 infection Interventional Study: In order to be eligible to participate in the registry study, and individual must meet all of the inclusion criteria of the registry study plus the following criteria: Hospitalized at NYU Tisch History of diabetes mellitus or blood glucose measurement >126 mg/dl AND EITHER History of hypertension and/or ischemic heart disease and/or heart failure OR Other co-morbid condition that in the opinion of the PI increases risk of heart or lung injury related to the aldose reductase pathway Exclusion Criteria Registry Study: An individual who meets any of the following criteria will be excluded from participation in the registry study: Persons who have opted out of research participation at NYU Pregnancy Interventional study: An individual who meets any of the following criteria will be excluded from participation in the interventional study: Persons who have opted out of research participation at NYU Pregnancy Women of childbearing potential Breast-feeding women Participation in another investigational drug protocol within previous 30 days

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: All subjects hospitalized with COVID-19 infection hospitalized will be enrolled in the registry; a subgroup meeting specific entry criteria listed below will be enrolled in the open-label interventional trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interventional Patients: AT-001<br>AT-001 1500 mg (3 capsules) were administered by mouth twice daily for up to 14 days | Drug: AT-001<br>* Investigational novel Aldose Reductase Inhibitor (ARI) Product: AT-001 500mg capsule for oral administration Dosage: 1,500mg (3X500mg capsules) twice daily Mode of Administration: Oral Up to 14 days per discretion of the investigators and treatment team<br>|
| No Intervention: Control Match Group 1<br>Matched control from a contemporaneous de-identified registry of hospitalized patients with clinical COVID-19 diagnosis at the same institution was selected. The first matching approach selected all subjects with diabetes mellitus and hypertension, and available data to match participants who received AT-001 for gender, age group (in bins of 5 years), weight, and C-reactive protein (CRP) value at the time of hospital admission. | |
| No Intervention: Control Match Group 2<br>Matched control from a contemporaneous de-identified registry of hospitalized patients with clinical COVID-19 diagnosis at the same institution was selected. The second matching approach selected all subjects in the registry with diabetes mellitus and available data to match participants who received AT-001 for gender, age group (in bings of 5 years), and weight (+/- 0.5 kgs). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital Length of Stay (LOS) | Data collection from medical chart review | Day 45 | 
| Percentage of Participants Who Died | Data collection from medical chart review | Day 45 |