Cardiovascular Effects of COVID-19

• Sponsor: NYU Langone Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT04365699
• Collaborator: (none)
• Enrollment: 81
• Location: 1
• Arms: 3
• Actual Duration (Months): 9.8
• Patients Per Site Per Month: 8.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Drug: AT-001	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 81 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• 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 trialAll 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)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Apr 8, 2020
• Actual Primary Completion Date: Jan 31, 2021
• Actual Study Completion Date: Jan 31, 2021

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures

1. Hospital Length of Stay (LOS) [Day 45]

   Data collection from medical chart review

2. Percentage of Participants Who Died [Day 45]

   Data collection from medical chart review

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	NYU Langone Health	New York	New York	United States	10016

Sponsors and Collaborators

• NYU Langone Health

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 3, 2020

More Information

Publications

None provided.

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT04365699
• Other Study ID Numbers: 20-00416
• First Posted: Apr 28, 2020
• Last Update Posted: Sep 16, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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
• Additional relevant MeSH terms: COVID-19

Study Results

Participant Flow

Arm/Group Title	Interventional Patients: AT-001	Control Match Group 1	Control Match Group 2
Arm/Group Description	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	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.	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).
Period Title: Overall Study
STARTED	10	16	55
COMPLETED	8	11	40
NOT COMPLETED	2	5	15

Baseline Characteristics

Arm/Group Title	Interventional Patients: AT-001	Control Match Group 1	Control Match Group 2	Total
Arm/Group Description	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	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.	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).	Total of all reporting groups
Overall Participants	10	16	55	81
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.4 (6.6)	65 (7.7)	64.5 (5.3)	64.8 (5.9)
Sex: Female, Male (Count of Participants)
Female	2 20%	2 12.5%	11 20%	15 18.5%
Male	8 80%	14 87.5%	44 80%	66 81.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	10 100%	16 100%	55 100%	81 100%
Region of Enrollment (participants) [Number]
United States	10 100%	16 100%	55 100%	81 100%

Outcome Measures

1. Primary Outcome

Title	Hospital Length of Stay (LOS)
Description	Data collection from medical chart review
Time Frame	Day 45

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Interventional Patients: AT-001	Control Match Group 1	Control Match Group 2
Arm/Group Description	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	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.	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).
Measure Participants	10	16	55
Median (95% Confidence Interval) [days]	5	10	25

2. Primary Outcome

Title	Percentage of Participants Who Died
Description	Data collection from medical chart review
Time Frame	Day 45

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Interventional Patients: AT-001	Control Match Group 1	Control Match Group 2
Arm/Group Description	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	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.	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).
Measure Participants	10	16	55
Number [percentage of participants]	20 200%	31.3 195.6%	27.3 49.6%

Adverse Events

Time Frame	45 days
Arm/Group Title	Interventional Patients: AT-001		Control Match Group 1		Control Match Group 2
Arm/Group Description	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		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.		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).
All Cause Mortality
	Interventional Patients: AT-001		Control Match Group 1		Control Match Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/10 (20%)		5/16 (31.3%)		15/55 (27.3%)
Serious Adverse Events
	Interventional Patients: AT-001		Control Match Group 1		Control Match Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/16 (0%)		0/55 (0%)
Other (Not Including Serious) Adverse Events
	Interventional Patients: AT-001		Control Match Group 1		Control Match Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/10 (30%)		0/16 (0%)		0/55 (0%)
Gastrointestinal disorders
Nausea / Upset GI	2/10 (20%)		0/16 (0%)		0/55 (0%)
Skin and subcutaneous tissue disorders
Localized Skin Rash	1/10 (10%)		0/16 (0%)		0/55 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.