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

NCT ID: NCT04363840

Last Updated: 2021-12-27

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-31
• Study Completion Date: 2020-12-31

Brief Summary

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

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.

Conditions

COVID; Vitamin D Deficiency; Coagulopathy; Disseminated Intravascular Coagulation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Observation

Group Type: NO_INTERVENTION

No interventions assigned to this group

Aspirin 81 mg

Group Type: EXPERIMENTAL

Aspirin 81 mg

Intervention Type: DRUG

Aspirin 81 mg to be taken orally once daily for 14 days.

Aspirin + vitamin D

Offered to COVID-19 patients who are vitamin D deficient AND randomized to aspirin

Group Type: EXPERIMENTAL

Aspirin 81 mg

Intervention Type: DRUG

Aspirin 81 mg to be taken orally once daily for 14 days.

Vitamin D

Intervention Type: DIETARY_SUPPLEMENT

Vitamin D 50,000 IU to be taken orally once weekly for 2 weeks

Interventions

Aspirin 81 mg

Aspirin 81 mg to be taken orally once daily for 14 days.

Intervention Type: DRUG

Vitamin D

Vitamin D 50,000 IU to be taken orally once weekly for 2 weeks

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Louisiana State University Health Sciences Center in New Orleans

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Frank H Lau, MD

Role: PRINCIPAL_INVESTIGATOR

LSUHSC-NO

References

Fischer AL, Messer S, Riera R, Martimbianco ALC, Stegemann M, Estcourt LJ, Weibel S, Monsef I, Andreas M, Pacheco RL, Skoetz N. Antiplatelet agents for the treatment of adults with COVID-19. Cochrane Database Syst Rev. 2023 Jul 25;7(7):CD015078. doi: 10.1002/14651858.CD015078.

Reference Type: DERIVED

PMID: 37489818 (View on PubMed)

Other Identifiers

20-063

Identifier Type: -

Identifier Source: org_study_id