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

• ClinicalTrials.gov Identifier: NCT04363840
• Recruitment Status: Not yet recruiting
• First Posted: April 27, 2020
• Last Update Posted: April 27, 2020
• Sponsor: Louisiana State University Health Sciences Center in New Orleans
• Information provided by (Responsible Party): Louisiana State University Health Sciences Center in New Orleans

Tracking Information

• First Submitted Date: April 24, 2020
• First Posted Date: April 27, 2020
• Last Update Posted Date: April 27, 2020
• Estimated Study Start Date: May 2020
• Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 24, 2020)

Hospitalization [ Time Frame: 2 weeks ]

Hospitalization for COVID-19 symptoms

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• COVID
• Vitamin D Deficiency
• Coagulopathy
• Disseminated Intravascular Coagulation

Intervention

• 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

Study Arms

• No Intervention: Observation
• Experimental: Aspirin 81 mg
  Intervention: Drug: Aspirin 81 mg
• Experimental: Aspirin + vitamin D
  Offered to COVID-19 patients who are vitamin D deficient AND randomized to aspirin
  Interventions:

  • Drug: Aspirin 81 mg
  • Dietary Supplement: Vitamin D

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: April 24, 2020): 1080
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2020
• Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Frank H Lau, MD; 504 412 1240; flau@lsuhsc.edu

• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT04363840
• Other Study ID Numbers: 20-063
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Responsible Party: Louisiana State University Health Sciences Center in New Orleans
• Study Sponsor: Louisiana State University Health Sciences Center in New Orleans
• Collaborators: Not Provided

Investigators

• Principal Investigator: Frank H Lau, MD; LSUHSC-NO

• PRS Account: Louisiana State University Health Sciences Center in New Orleans
• Verification Date: April 2020