The LEAD COVID-19 Trial: Low-risk, Early Aspirin and Vitamin D to Reduce COVID-19 Hospitalizations (LEAD COVID-19)

Although the novel SARS-CoV-2 virus (COVD-19) is classified as an acute respiratory infection, emerging data show that morbidity and mortality are driven by disseminated intravascular coagulopathy. Untreated CAC leads to microangiopathic thromboses, causing multiple systems organ failure and consuming enormous healthcare resources. Identifying strategies to prevent CAC are therefore crucial to reducing COVID-19 hospitalization rates.

The pathogenesis of CAC is unknown, but there are major overlaps between severe COVID-19 and vitamin D insufficiency (VDI). We hypothesize that VDI is a major underlying contributor to CAC. Preliminary data from severe COVID-19 patients in New Orleans support this hypothesis. The purpose of the proposed multi-center, prospective, randomized controlled trial is to test the hypothesis that low-risk, early treatment with aspirin and vitamin D in COVID-19 can mitigate the prothrombotic state and reduce hospitalization rates.

Study Overview

• Status: Withdrawn
• Conditions: Vitamin D Deficiency; COVID; Coagulopathy; Disseminated Intravascular Coagulation
• Intervention / Treatment: Drug: Aspirin 81 mg; Dietary supplement: Vitamin D

Detailed Description

Although the novel SARS-CoV-2 virus (COVD-19) is classified as an acute respiratory infection, emerging data show that morbidity and mortality are driven by disseminated intravascular coagulopathy. Data from Wuhan showed that COVID-19-associated coagulopathy (CAC) was present in 71% of deaths vs. 0.4% of survivors. Untreated CAC leads to microangiopathic thromboses, causing multiple systems organ failure and consuming enormous healthcare resources. Identifying strategies to prevent CAC are therefore crucial to reducing COVID-19 hospitalization rates.

The high prevalence of CAC in severely ill COVID-19 patients led the American Society of Hematology to recommend that all hospitalized COVID-19 patients be prophylactically anticoagulated. However, there are no data and no recommendations regarding outpatient prevention of CAC.

The pathogenesis of CAC is unknown. Given the demographic, geographic, pathologic, and treatment overlap between severe COVID-19 and vitamin D insufficiency (VDI), we hypothesize that VDI is a major underlying contributor to CAC. Preliminary data from critically ill COVID-19 patients in New Orleans support this hypothesis. Furthermore, mouse models of VDI developed aggravated multiorgan thrombus formation after lipopolysaccharide injection; this phenotype parallels CAC.

Given these lines of evidence, the purpose of the proposed multi-center, prospective, randomized controlled trial is to test the hypothesis that low-risk, early treatment with aspirin and vitamin D in COVID-19 (The LEAD COVID-19 Trial) can mitigate the prothrombotic state and reduce hospitalization rates.

• Study Type: Interventional
• Phase: Phase 2

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:

• Patients > 18 years
• Written informed consent
• New (within 24 hours) COVID-19 diagnosis

Exclusion Criteria:

• Pregnant patients or Prisoners
• History of GI bleeding or peptic ulcer disease, or spontaneous bleeding from other sites; History of thrombocytopenia; History of chronic kidney disease; Concurrent use of nonsteroidal anti-inflammatory drugs, or steroids.
• Hypervitaminosis D and associated risk factors: Renal failure, Liver failure, Hyperparathyroidism, Sarcoidosis, Histoplasmosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Observation
Experimental: Aspirin 81 mg	Drug: Aspirin 81 mg; Aspirin 81 mg to be taken orally once daily for 14 days.
Experimental: Aspirin + vitamin D; Offered to COVID-19 patients who are vitamin D deficient AND randomized to aspirin	Drug: Aspirin 81 mg; Aspirin 81 mg to be taken orally once daily for 14 days.; Dietary supplement: Vitamin D; Vitamin D 50,000 IU to be taken orally once weekly for 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalization	Hospitalization for COVID-19 symptoms	2 weeks

Collaborators and Investigators

• Sponsor: Louisiana State University Health Sciences Center in New Orleans
• Investigators: Principal Investigator: Frank H Lau, MD, Lsuhsc-No

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2020
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: April 24, 2020
• First Submitted That Met QC Criteria: April 24, 2020
• First Posted (Actual): April 27, 2020

Study Record Updates

• Last Update Posted (Actual): December 27, 2021
• Last Update Submitted That Met QC Criteria: December 7, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Nutrition Disorders; Hemorrhagic Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Blood Coagulation Disorders; Thrombophilia; Vitamin D Deficiency; Disseminated Intravascular Coagulation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Micronutrients; Vitamins; Bone Density Conservation Agents; Aspirin; Vitamin D
• Other Study ID Numbers: 20-063

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