Clinical trial NCT04410328: Aggrenox To Treat Acute Covid-19
Official title: A Randomized Controlled Trial to Evaluate the Outcomes With Aggrenox in Patients With SARS-CoV-2 Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Covid19
Keywords: COVID-19
SARS-CoV
Aggrenox
Dipyridamole
Aspirin
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
First posted: 2020-06-01
Enrollment: 98
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years.
2. Hospitalization.
3. SARS-CoV-2 viral nucleic acid positive within 3 days.
4. 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).
5. Willing and able to provide consent or by authorized proxy.

Exclusion Criteria:

1. Pregnancy.
2. G-6PD deficiency.
3. Use of antiplatelet agents including inhibitor of P2Y12 ADP platelet receptors, phosphodiesterase inhibitors, and Glycoprotein IIB/IIIA inhibitors.
4. On therapeutic anticoagulation with coumadin, heparin and direct oral anticoagulants.
5. Vasodilatory shock.
6. Patient with known ongoing angina, recent myocardial infarction and sub-valvular aortic stenosis.
7. Active gastric or duodenal ulcer or any bleeding disorder.
8. Hemoglobin \<9 mg/dL, platelet count of \<30,000 /mm3.
9. Acute respiratory infection for \>10 days.
10. Known allergy/hypersensitivity to Dipyridamole and/or Aspirin.
11. Severe hepatic or renal insufficiency.
12. Uncontrolled hypertension defined as systolic \> 180 mm Hg or diastolic \> 100 mm Hg.
13. Patients with known allergy to NSAIDs

Primary outcomes:
measure: Covid (Coronavirus Disease-19) Ordinal Scale
timeFrame: 15 days
Secondary outcomes:
measure: Mortality
timeFrame: 14 days
measure: Mortality
timeFrame: 28 days
measure: Inflammatory Marker Between Baseline and 7 Days
timeFrame: Baseline and 7 days
measure: COVID Ordinal Scale
timeFrame: 28 days
measure: Number of Participants Not Requiring Supplemental Oxygen
timeFrame: 28 days
measure: Invasive-ventilator
timeFrame: 28 days
measure: ICU Stay
timeFrame: 28 days
measure: Inflammatory Marker
timeFrame: Baseline and 7 days
measure: Inflammatory Marker
timeFrame: Baseline and 7 days
Other outcomes:
Locations:
city: Newark
country: United States
facility: Rutgers New Jersey Medical School University Hospital
state: New Jersey
Study officials:
affiliation: Rutgers University
name: Amit Singla, MD
role: PRINCIPAL_INVESTIGATOR
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