Trial of Open Label Dipyridamole- In Hospitalized Patients With COVID-19
Condition: COVID-19 Pneumonia; Vascular Complications
MeSH terms: COVID-19
Intervention: Placebo; Dipyridamole Tablets
Intervention description: Daily dose while hospitalized up to 9 days; Daily dose while hospitalized up to 9 days
Intervention MeSH terms: Dipyridamole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized Open Label Study Standard Care vs. Standard Care with Dipyridamole
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Brief Summary:

      The goal here is to evaluate dipyridamole in treating respiratory tract infection and
      circulatory dysfunction due to SARS-CoV-2 coronavirus in hospitalized CVID-19 patients.

      Infection with SARS-CoV-2 causes human COVID-19 (HCoV-19). The infection is associated with a
      deleterious inflammatory response and a prothrombotic state in addition to tissue damage from
      direct viral entry and proliferation. Dipyridamole has anti-platelet and anti-inflammatory
      effects. The drug was recently demonstrated to have anti-SARS-Cov-2 effect primarily in
      vitro. The concentration causing anti-viral effect in vitro is within that in the blood of
      humans taking this drug. As an oral tablet, it has the advantage of easy administration.

      Anti thrombotic, anti viral and anti inflammatory actions of this drug may be efficacious and
      safe in hospitalized subjects
    

Eligibility criteria:

        Inclusion Criteria:

          1. Adults ≥18 years of age.

          2. COVID-19 positive by PCR and hospitalized for respiratory infection with a range of
             respiratory severity as follows.

             Moderate ● Diagnosed with SARS-CoV-2 infection by standard RT-PCR assay or equivalent
             testing

             ● Symptoms of moderate illness with COVID-19, which could include:

             o Fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal
             symptoms; shortness of breath with exertion

               -  Clinical signs suggestive of moderate illness with COVID-19, such as:

                  o RR ≥ 20, HR ≥ 90, SaO2 ≥93% on room air or requires ≤2L oxygen by nasal cannula
                  (NC) in order maintain SaO2 ≥93%, fever >38.3 Celsius

               -  No clinical signs indicative of Severe or Critical Illness Severity

             Severe

               -  Diagnosed with SARS-CoV-2 infection by standard RT-PCR assay or equivalent
                  testing

               -  Symptoms suggestive of severe systemic illness with COVID-19, which could
                  include:

                  o any symptom of Moderate Illness; shortness of breath at rest or respiratory
                  distress

               -  Clinical signs indicative of severe systemic illness with COVID-19, such as

                  o RR ≥ 30, HR ≥ 125, requires > 2L oxygen by NC in order maintain SaO2 ≥93%,
                  PaO2/FiO2 <300

               -  No criteria for Critical Severity

             Critical ● Diagnosed with SARS-CoV-2 infection by standard RT-PCR assay or equivalent
             testing

               -  Evidence of critical illness, defined by at least 1 of the following:

                    -  Respiratory failure defined based on resource utilization requiring at least
                       1 of the following:

                       ◙, Oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen
                       delivered via reinforced nasal cannula at flow rates >20L/min with fraction
                       of delivered oxygen ≥0.5), noninvasive positive pressure ventilation, ECMO,
                       or clinical diagnosis of respiratory failure (i.e., clinical need for one of
                       the preceding therapies, but preceding therapies not able to be administered
                       in setting of resource limitation)

                    -  Shock (defined by SBP < 90 mm Hg, or Diastolic BP < 60 mm Hg or requiring
                       vasopressors)

                    -  Multiple organ dysfunction/failure

          3. Able to give written informed consent in English to participate in the study by
             patient.

             -

        Exclusion Criteria:

          -  Exclusion Criteria:

               1. Inability to swallow or ingest oral medication in either tablet form or in
                  suspension form.

               2. Patient is known to be pregnant

               3. Patients with a history of allergy or hypersensitivity to dipyridamole

               4. Patient is unable to consent -intubated, on mechanical ventilation

               5. Bleeding disorders (e.g. thrombocytopenia with platelet counts < 50,000)

               6. Existing severe medical illnesses unrelated to Covid-19 infection such as end
                  stage heart, kidney, liver disorders;

                  or hepatic insufficiency defined as liver enzymes ≥5 times upper limit normal if
                  baseline is normal or 5 times baseline if baseline is abnormal.

                  Metastatic cancer as well as those with severe coronary artery disease, unstable
                  angina, STEMI, NSTEMI, hypotension (systolic blood pressure <90mmHg),
                  myocarditis, bradycardia with resting heart rate less than 60 bpm,
                  atrioventricular block without pacemaker.

                  Those with myasthenia gravis and those treated with cholinesterase inhibitors

               7. Patient is enrolled in a clinical trial for another investigational drug designed
                  to test for efficacy for SARS-CoV-2