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
The original protocol stipulated an enrollment of 100 patients, randomized in a 1 to 1
distribution of treatment versus control [placebo] group. However, the study was terminated
because of insufficient enrollment due to the dramatic reduction in the number of
hospitalized COVID patients.
A total of 41 patients were randomized prior to study termination. Detailed reports and
overall results were reviewed for all patients.
Adverse event occurrences were similar in groups. Given the severity of COVID, these numbers
were not unexpected.
The DSMC concluded that all the AEs seen in study subjects are either unrelated or probably
unrelated to the TOLD study intervention.
The DSMC reviewed the primary outcome results. No statistically significant change in either
the platelet count or the D-dimer results.
Drug: Placebo
Daily dose while hospitalized up to 9 days
Drug: Dipyridamole Tablets
Daily dose while hospitalized up to 9 days
Other Name: Persantine
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
UConn Health
Farmington, Connecticut, United States
Bruce Liang, MD, Principal Investigator
UConn Health