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.
The objectives of this study are: - To characterize serial measures cardiac structure and function and in-hospital survival in hospitalized patients with COVID-19 infection - To develop predictive models of cardiac risk in hospitalized COVID-19 infection patients - To assess safety of treatment with AT-001 plus standard of care on in-hospital survival in patients with COVID-19 - To characterize the effects of treatment with AT-001 plus standard of care on in-hospital mortality, progression of acute lung injury requiring mechanical ventilation, and serial measures of cardiac structure and function
Drug: AT-001
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
Inclusion Criteria
Registry Study: In order to be eligible to participate in the registry study, an individual
must meet all of the following criteria:
1. Age ≥18 years of age
2. Hospitalized at one of the participating NYULH locations
3. 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:
1. Hospitalized at NYU Tisch
2. History of diabetes mellitus or blood glucose measurement >126 mg/dl AND EITHER
3. History of hypertension and/or ischemic heart disease and/or heart failure OR
4. 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:
1. Persons who have opted out of research participation at NYU
2. Pregnancy
Interventional study: An individual who meets any of the following criteria will be
excluded from participation in the interventional study:
1. Persons who have opted out of research participation at NYU
2. Pregnancy
3. Women of childbearing potential
4. Breast-feeding women
5. Participation in another investigational drug protocol within previous 30 days
NYU Langone Health
New York, New York, United States
Stuart Katz, MD, Principal Investigator
NYU Langone Health