Aggrenox To Treat Acute Covid-19

Study Overview
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Brief Summary
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The purpose of this study is to explore the efficacy of Aggrenox in patients with SARS-CoV-2 infection with symptoms consistent with COVID-19. An anticipated total of 132 participants will be randomly divided almost equally into 2 groups: one group will receive Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally along with the standard of care and the other group with receive the standard of care only but no Dipyridamole ER 200mg/ Aspirin 25mg. Participants will be screened, enrolled, receive treatment, and followed for 28 days. The clinical and laboratory outcomes of all the participants enrolled in the study will be evaluated at the end of the study to explore if there is any difference in the outcomes between 2 groups.

Detailed Description
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Purpose/Specific Aims: The purpose of this study is to explore the efficacy of Aggrenox in patients with SARS-CoV-2 infection with symptoms consistent with COVID-19. Among 132 SARS-CoV-2 patients (66 patients in each randomized arm), we will determine the efficacy of Aggrenox on clinical outcomes. Hypotheses / Research Question(s) Compared to standard care, the addition of Aggrenox (Dipyridamole ER 200mg/ Aspirin 25mg), to standard care will result in improvement in the composite COVID ordinal scale at day 15. Additionally, combined Aggrenox (Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally), and standard care will reduce the need for ventilation, length of mechanical ventilation, hospital length of stay, ICU length of stay, decrease risk of thromboembolic complications and improve survival more than standard care alone in SARS-CoV-2 patients. Research Design and Methods Randomized design. Participants will be randomized 1:1 to Aggrenox or standard treatment. Arm 1: Active Comparator: (Aggrenox (Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally). Participants will receive Aggrenox (Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally), 2 times daily (FDA-recommended dose) starting on the day of enrollment for a total of 2 weeks + standard care. Arm 2: Standard care Comparator: Participants will receive standard care starting on the day of enrollment for a total of 2 weeks. The investigators will perform a randomized, 2-arm, open-label single-site pilot study to evaluate the effect of oral Aggrenox (Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally), on clinical outcomes in patients with SARS-CoV-2. In this research proposal, investigators will randomly assign 132 consenting participants with diagnosis of SARS-CoV-2 to two treatment groups: 1) Aggrenox (Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally) + standard care and 2) standard care alone. Participants will be screened, enrolled, receive treatment and followed for 28 days. The study aim and procedure will be explained to every eligible subject and informed consent will be obtained from interested subjects or authorized proxy to participate in the study. The investigators will collect demographic, clinical, laboratory and radiological data. The patients would be followed daily for 2 weeks after enrollment while the patient is in the hospital and once discharged, they will be called every 3rd day to follow up on the symptoms.

Official Title
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A Randomized Controlled Trial to Evaluate the Outcomes With Aggrenox in Patients With SARS-CoV-2 Infection

Conditions
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Covid19

Intervention / Treatment
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* Drug: Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally AND Standard of care
* Other: Standard of care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years. Hospitalization. SARS-CoV-2 viral nucleic acid positive within 3 days. Lab test result pending plus a high clinical suspicion for SARS-CoV-2 (fever and cough for ≤ 7 days, bilateral pulmonary infiltrates on imaging or new hypoxemia with spO2 ≤94% on room air or no alternative explanation for respiratory symptoms). Willing and able to provide consent or by authorized proxy. Exclusion Criteria: Pregnancy. G-6PD deficiency. Use of antiplatelet agents including inhibitor of P2Y12 ADP platelet receptors, phosphodiesterase inhibitors, and Glycoprotein IIB/IIIA inhibitors. On therapeutic anticoagulation with coumadin, heparin and direct oral anticoagulants. Vasodilatory shock. Patient with known ongoing angina, recent myocardial infarction and sub-valvular aortic stenosis. Active gastric or duodenal ulcer or any bleeding disorder. Hemoglobin <9 mg/dL, platelet count of <30,000 /mm3. Acute respiratory infection for >10 days. Known allergy/hypersensitivity to Dipyridamole and/or Aspirin. Severe hepatic or renal insufficiency. Uncontrolled hypertension defined as systolic > 180 mm Hg or diastolic > 100 mm Hg. Patients with known allergy to NSAIDs

Ages Eligible for Study
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Minimum Age: 19 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
Interventional Model Description: Arm 1: Aggrenox plus standard care. Participants will receive Aggrenox (Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally), 2 times daily (FDA-recommended dose) starting on the day of enrollment for a total of 2 weeks. Arm 2: Standard care. Participants will receive standard care starting on the day of enrollment for a total of 2 weeks. The investigators will perform a randomized, 2-arm, open-label single-site pilot study to evaluate the effect of oral Aggrenox (Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally), on clinical outcomes in patients with SARS-CoV-2. In this research proposal, the investigators will randomly assign 132 consenting participants with diagnosis of SARS-CoV-2 to two treatment groups: 1) Aggrenox (Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally) + standard care and 2) standard care alone. Participants will be screened, enrolled, receive treatment and followed for 28 days.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants receiving Dipyridamole and Aspirin<br>Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally plus standard care. Participants will receive Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally), 2 times daily starting on the day of enrollment for a total of 2 weeks. | Drug: Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally AND Standard of care<br>* Participants in the experimental group will receive Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally (if they have a feeding tube), 2 times daily starting on the day of enrollment for a total of 2 weeks.<br>* Other names: Aggrenox;Other: Standard of care<br>* Participants will receive standard care starting on the day of enrollment for a total of 2 weeks.<br>|
| Other: Participants receiving standard of care<br>Participants will receive standard care starting on the day of enrollment for a total of 2 weeks. | Other: Standard of care<br>* Participants will receive standard care starting on the day of enrollment for a total of 2 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Covid (Coronavirus Disease-19) Ordinal Scale | Change in composite COVID ordinal scale at day 15. Ordinal scale: 1) not hospitalized with resumption of normal activities; 2) not hospitalized, but unable to resume normal activities; 3) hospitalized, not requiring oxygen; 4) hospitalized, requiring oxygen; 5) hospitalized, requiring high-flow oxygen therapy, or noninvasive ventilation; 6) hospitalized, requiring invasive ventilation; 7) ventilation plus additional organ support such as pressors, renal replacement therapy and ECMO and 8) death. COVID Ordinal Scale ranges from 1 to 8, with score 1 on the scale corresponds to an ambulatory patient with minimal symptoms and score 8 on the scale corresponds to death. | 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | All-cause mortality assessed on day 15. | 15 days | 
| Mortality | All-cause mortality assessed on day 28. | 28 days | 
| Supplemental Oxygen | Supplemental Oxygen-free days | 28 days | 
| Invasive-ventilator | Invasive-ventilator-free days | 28 days | 
| ICU stay | ICU-free days | 28 days | 
| Hospital stay | Hospital-free days | 28 days | 
| Inflammatory markers | Decrease in the markers D-dimer/ Ferritin/ C-reactive protein | 15 days | 
| Thromboembolic complications | Thromboembolic complications including stroke | 28 days | 
| COVID ordinal scale | COVID ordinal scale | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, SARS-CoV, Aggrenox, Dipyridamole, Aspirin