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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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COVID, Vitamin D Deficiency, Coagulopathy, Disseminated Intravascular Coagulation

Intervention / Treatment
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* Drug: Aspirin 81 mg
* Dietary Supplement: Vitamin D


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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