Cardiovascular Effects of COVID-19

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

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.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: AT-001

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Interventional Patients: AT-001; AT-001 1500 mg (3 capsules) were administered by mouth twice daily for up to 14 days	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
No Intervention: 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.
No Intervention: 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).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Stuart Katz, MD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2020
• Primary Completion (Actual): January 31, 2021
• Study Completion (Actual): January 31, 2021

Study Registration Dates

• First Submitted: April 25, 2020
• First Submitted That Met QC Criteria: April 25, 2020
• First Posted (Actual): April 28, 2020

Study Record Updates

• Last Update Posted (Actual): September 16, 2021
• Last Update Submitted That Met QC Criteria: September 10, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: 20-00416

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The de-identified participant data from the final research dataset used in the published manuscript will be shared upon reasonable request beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to Stuart.Katz@nyulangone.org. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication
• IPD Sharing Access Criteria: Requests may be directed to Stuart.Katz@nyulangone.org.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes