TOLD: Trial of Open Label Dipyridamole- In Hospitalized Patients With COVID-19
Study Details
Study Description
Brief 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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| No Intervention: Standard Care Hospitalized patients meeting screen criteria receive standard Hospital care from which clinical event and lab data are collected. Day 3,6 & 9 research samples will be used for obtaining immunological profiles as well as metabolomic profiling and whole genome sequencing for discovery of new biomarkers/ genomic regions that confer increased susceptibility to infection and DIP treatment efficacy or safety. Other samples will be obtained for microbiome and viral analyses. Data collection ends on day 9. |
|
| Experimental: Standard Care with Dipyridamole For this arm, Dipyridamole 100 mg, tid is given for 7 days. Hospitalized patients meeting screen criteria receive standard Hospital care from which clinical event and lab data are collected. Day 3,6 & 9 research samples will be used for obtaining immunological profiles as well as metabolomic profiling and whole genome sequencing for discovery of new biomarkers/ genomic regions that confer increased susceptibility to infection and DIP treatment efficacy or safety. Other samples will be obtained for microbiome and viral analyses. Data collection ends on day 9. |
Drug: Dipyridamole
Dipyridamole-100mg taken 3 times a day by mouth for 7 days.
|
Outcome Measures
Primary Outcome Measures
- Coagulation system [9 days]
D-dimer
- Coagulation system [9 days]
Platelet Count
Secondary Outcome Measures
- Viral Detection [9 days]
Evaluate for a non-detection from nasopharyngeal swab and in stool
Other Outcome Measures
- Survival [9 days]
Survival Status Alive
- Inflammatory Markers [9 days]
Change in the markers CRP/Ferritin
- Blood Markers [9 days]
Change in Lymphocyte Count/ Fibrinogen/Cardiac Troponin
- Coagulation Markers [9 days]
Change in PT, PTT
- Pulmonary Status [9 days]
Change in SpO2/ imaging
- Clinical Status [9 days]
Change in fever, cough, sputum
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Adults ≥18 years of age.
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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:
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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)
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Shock (defined by SBP < 90 mm Hg, or Diastolic BP < 60 mm Hg or requiring vasopressors)
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Multiple organ dysfunction/failure
- Able to give written informed consent in English to participate in the study by patient.
Exclusion Criteria:
- Exclusion Criteria:
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Inability to swallow or ingest oral medication in either tablet form or in suspension form.
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Patient is known to be pregnant
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Patients with a history of allergy or hypersensitivity to dipyridamole
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Patient is unable to consent -intubated, on mechanical ventilation
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Bleeding disorders (e.g. thrombocytopenia with platelet counts < 50,000)
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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
- Patient is enrolled in a clinical trial for another investigational drug designed to test for efficacy for SARS-CoV-2
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UConn Health | Farmington | Connecticut | United States | 06030 |
Sponsors and Collaborators
- UConn Health
Investigators
- Principal Investigator: Bruce Liang, MD, UConn Health
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 20-192-2.F