COVID-19
Conditions
Brief summary
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.
Interventions
DRUGAT-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
Sponsors
NYU Langone Health
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention 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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hospital Length of Stay (LOS) | Day 45 | Data collection from medical chart review |
| Percentage of Participants Who Died | Day 45 | Data collection from medical chart review |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Interventional Patients: AT-001 Patients enrolled in registry from NYU Langone Tisch Hospital with history of diabetes mellitus and/or acute hyperglycemia (any glucose measurement \>200 mg/dl) and evidence of acute or chronic heart disease. This subset will receive Standard of Care + AT-001.
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 | 10 |
| Control Match Group 1 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. | 16 |
| Control Match Group 2 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). | 55 |
| Total | 81 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 2 | 5 | 15 |
Baseline characteristics
| Characteristic | Interventional Patients: AT-001 | Total | Control Match Group 2 | Control Match Group 1 |
|---|---|---|---|---|
| Age, Continuous | 66.4 years STANDARD_DEVIATION 6.6 | 64.8 years STANDARD_DEVIATION 5.9 | 64.5 years STANDARD_DEVIATION 5.3 | 65 years STANDARD_DEVIATION 7.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 10 Participants | 81 Participants | 55 Participants | 16 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 10 participants | 81 participants | 55 participants | 16 participants |
| Sex: Female, Male Female | 2 Participants | 15 Participants | 11 Participants | 2 Participants |
| Sex: Female, Male Male | 8 Participants | 66 Participants | 44 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 10 | 5 / 16 | 15 / 55 |
| other Total, other adverse events | 3 / 10 | 0 / 16 | 0 / 55 |
| serious Total, serious adverse events | 0 / 10 | 0 / 16 | 0 / 55 |
Outcome results
Primary
Hospital Length of Stay (LOS)
Data collection from medical chart review
Time frame: Day 45
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Interventional Patients: AT-001 | Hospital Length of Stay (LOS) | 5 days |
| Control Match Group 1 | Hospital Length of Stay (LOS) | 10 days |
| Control Match Group 2 | Hospital Length of Stay (LOS) | 25 days |
Primary
Percentage of Participants Who Died
Data collection from medical chart review
Time frame: Day 45
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Interventional Patients: AT-001 | Percentage of Participants Who Died | 20 percentage of participants |
| Control Match Group 1 | Percentage of Participants Who Died | 31.3 percentage of participants |
| Control Match Group 2 | Percentage of Participants Who Died | 27.3 percentage of participants |