Aggrenox To Treat Acute Covid-19

Phase 3

Completed

Conditions: Covid19

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

Registration Number: NCT04410328

Lead Sponsor: Rutgers, The State University of New Jersey

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 98

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Participants receiving Dipyridamole and Aspirin	Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally AND Standard of care	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.
Participants receiving standard of care	Standard of care	Participants will receive standard care starting on the day of enrollment for a total of 2 weeks. Standard of care treatment consist of an intravenous Remidesivir 200 mg loading dose and then 100 mg/daily for a total of 4 days for non-intubated patients and 10 days for intubated patients, intravenous/oral decadron 6 mg/daily for 10 days and prophylactic subcutaneous LMWH daily, started on the day of enrollment and for the duration of hospitalization. If the patients are discharged before 10 days, they are prescribed oral decadron 6 mg daily to complete the course of 10 days.
Participants receiving Dipyridamole and Aspirin	Standard of care	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.

Primary Outcome Measures

Name	Time	Method
Covid (Coronavirus Disease-19) Ordinal Scale	15 days	Change in composite COVID ordinal scale from day 1 to 14. 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.

Secondary Outcome Measures

Name	Time	Method
Inflammatory Marker	Baseline and 7 days	Increase in marker C-reactive protein
COVID Ordinal Scale	28 days	COVID ordinal scale
ICU Stay	28 days	Number of participants admitted to ICU
Number of Participants Not Requiring Supplemental Oxygen	28 days	number of participants who received supplemental oxygen or those with supplemental oxygen-free days
Invasive-ventilator	28 days	Number of participants who were invasive-ventilator free
Mortality	28 days	All-cause mortality assessed on day 28.
Inflammatory Marker Between Baseline and 7 Days	Baseline and 7 days	Change in marker D-dimer