Covid19
Conditions
Keywords
COVID-19, SARS-CoV, Aggrenox, Dipyridamole, Aspirin
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.
Interventions
DRUGDipyridamole ER 200mg/ Aspirin 25mg orally/enterally AND Standard of care
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.
OTHERStandard 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.
Sponsors
Boehringer Ingelheim
Rutgers, The State University of New Jersey
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Inflammatory Marker Between Baseline and 7 Days | Baseline and 7 days | Change in marker D-dimer |
| COVID Ordinal Scale | 28 days | COVID ordinal scale |
| Number of Participants Not Requiring Supplemental Oxygen | 28 days | number of participants who received supplemental oxygen or those with supplemental oxygen-free days |
| Mortality | 14 days | All-cause mortality assessed on day 14. |
| ICU Stay | 28 days | Number of participants admitted to ICU |
| Inflammatory Marker | Baseline and 7 days | Increase in marker Ferritin |
| Invasive-ventilator | 28 days | Number of participants who were invasive-ventilator free |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Participants Receiving Dipyridamole and Aspirin 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.
Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally AND Standard of care: 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.
Standard of care: Participants will receive standard care starting on the day of enrollment for a total of 2 weeks. | 49 |
| Participants Receiving Standard of Care Participants will receive standard care starting on the day of enrollment for a total of 2 weeks.
Standard of care: Participants will receive standard care starting on the day of enrollment for a total of 2 weeks. | 49 |
| Total | 98 |
Baseline characteristics
| Characteristic | Participants Receiving Dipyridamole and Aspirin | Total | Participants Receiving Standard of Care |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 49 Participants | 98 Participants | 49 Participants |
| Age, Continuous | 57.5 years | 57 years | 56 years |
| Race/Ethnicity, Customized Aboriginal/First Nations | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black | 9 Participants | 18 Participants | 9 Participants |
| Race/Ethnicity, Customized East Asian | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Latin American | 10 Participants | 20 Participants | 10 Participants |
| Race/Ethnicity, Customized Mixed | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 5 Participants | 3 Participants |
| Race/Ethnicity, Customized South Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown | 27 Participants | 52 Participants | 25 Participants |
| Race/Ethnicity, Customized West Asian | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment United States | 49 participants | 98 participants | 49 participants |
| Sex: Female, Male Female | 31 Participants | 52 Participants | 21 Participants |
| Sex: Female, Male Male | 18 Participants | 46 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 49 | 7 / 49 |
| other Total, other adverse events | 0 / 49 | 0 / 49 |
| serious Total, serious adverse events | 5 / 49 | 7 / 49 |
Outcome results
Primary
Covid (Coronavirus Disease-19) Ordinal Scale
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.
Time frame: 15 days
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Participants Receiving Dipyridamole and Aspirin | Covid (Coronavirus Disease-19) Ordinal Scale | 2.3 score on a scale | Standard Deviation 1.8 |
| Participants Receiving Standard of Care | Covid (Coronavirus Disease-19) Ordinal Scale | 2.1 score on a scale | Standard Deviation 2 |
Secondary
COVID Ordinal Scale
COVID ordinal scale
Time frame: 28 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants Receiving Dipyridamole and Aspirin | COVID Ordinal Scale | 3 scores on a scale |
| Participants Receiving Standard of Care | COVID Ordinal Scale | 3 scores on a scale |
Secondary
ICU Stay
Number of participants admitted to ICU
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants Receiving Dipyridamole and Aspirin | ICU Stay | 5 Participants |
| Participants Receiving Standard of Care | ICU Stay | 7 Participants |
Secondary
Inflammatory Marker
Increase in marker C-reactive protein
Time frame: Baseline and 7 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants Receiving Dipyridamole and Aspirin | Inflammatory Marker | 92 ug/L |
| Participants Receiving Standard of Care | Inflammatory Marker | 165 ug/L |
Secondary
Inflammatory Marker
Increase in marker Ferritin
Time frame: Baseline and 7 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants Receiving Dipyridamole and Aspirin | Inflammatory Marker | 652.5 ug/L |
| Participants Receiving Standard of Care | Inflammatory Marker | 381 ug/L |
Secondary
Inflammatory Marker Between Baseline and 7 Days
Change in marker D-dimer
Time frame: Baseline and 7 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants Receiving Dipyridamole and Aspirin | Inflammatory Marker Between Baseline and 7 Days | -197.5 ng/mL |
| Participants Receiving Standard of Care | Inflammatory Marker Between Baseline and 7 Days | 114 ng/mL |
Secondary
Invasive-ventilator
Number of participants who were invasive-ventilator free
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants Receiving Dipyridamole and Aspirin | Invasive-ventilator | 4 Participants |
| Participants Receiving Standard of Care | Invasive-ventilator | 5 Participants |
Secondary
Mortality
All-cause mortality assessed on day 28.
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants Receiving Dipyridamole and Aspirin | Mortality | 3 Participants |
| Participants Receiving Standard of Care | Mortality | 5 Participants |
Secondary
Mortality
All-cause mortality assessed on day 14.
Time frame: 14 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants Receiving Dipyridamole and Aspirin | Mortality | 2 Participants |
| Participants Receiving Standard of Care | Mortality | 2 Participants |
Secondary
Number of Participants Not Requiring Supplemental Oxygen
number of participants who received supplemental oxygen or those with supplemental oxygen-free days
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants Receiving Dipyridamole and Aspirin | Number of Participants Not Requiring Supplemental Oxygen | 45 Participants |
| Participants Receiving Standard of Care | Number of Participants Not Requiring Supplemental Oxygen | 43 Participants |