COVID-19 PneumoniaPhase 2TOLDNCT04424901
Trial of Open Label Dipyridamole- In Hospitalized Patients With COVID-19
A Phase 2 study testing Dipyridamole Tablets in people with COVID-19 Pneumonia and Vascular Complications, run by UConn Health at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19 Pneumonia, Vascular Complications
- What is being tested?
- Dipyridamole Tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- 3 May 2020to 24 Apr 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults ≥18 years of age.
- 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:
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- 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
- Able to give written informed consent in English to participate in the study by patient.
- -
Who cannot join
- Inability to swallow or ingest oral medication in either tablet form or in suspension form.
- Patient is known to be pregnant
- Patients with a history of allergy or hypersensitivity to dipyridamole
- Patient is unable to consent -intubated, on mechanical ventilation
- Bleeding disorders (e.g. thrombocytopenia with platelet counts < 50,000)
- Existing severe medical illnesses unrelated to Covid-19 infection such as end stage heart, kidney, liver disorders;
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Open-label Study of the Vascular and Microbiologic Efficacy of Dipyridamole Plus Standard Care vs. Standard Care in Hospitalized COVID19 Patients
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.
Read more
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
Read the detailed description
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.
- Conditions
- COVID-19 Pneumonia, Vascular Complications
- Being tested
- Placebo, Dipyridamole Tablets
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Daily dose while hospitalized up to 9 days
Dipyridamole TabletsDrug
Also called Persantine
Daily dose while hospitalized up to 9 days
| Study group | Role | What they receive |
|---|---|---|
| Standard Care | Placebo comparator | 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. Receives: Drug: Placebo |
| Standard Care with Dipyridamole | Experimental | 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. Receives: Drug: Dipyridamole Tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
D-dimer
Percent Change from Baseline [Day Zero] to last study measure (Day 3, Day 6 or Day 9)
Measured: up to 9 days
Platelet Count
Percent Change from Baseline [Day Zero] to last study measure (Day 3, Day 6 or Day 9)
Measured: up to 9 days
Secondary outcomes (1)
Viral Detection
Evaluate for a non-detection from nasopharyngeal swab and in stool
Measured: 9 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2020
- Study start3 May 2020
- Primary completion22 Mar 2022
- Study completion24 Apr 2022
Why it stopped: reduction of Hospitalized COVID patients at UConnHealth
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for COVID-19 PneumoniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized Open Label Study Standard Care vs. Standard Care with Dipyridamole
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- UConn Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bruce Liang, UConn Health
- Investigators
- Bruce Liang, MD, Principal investigator, UConn Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04424901
- Sponsor's protocol ID
- 20-192-2.F
- Acronym
- TOLD
- Status last verified
- Apr 2023
- First submitted
- 29 May 2020
- Last updated
- 21 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-label Study of the Vascular and Microbiologic Efficacy of Dipyridamole Plus Standard Care vs. Standard Care in Hospitalized COVID19 Patients
- ClinicalTrials.gov ID
- NCT04424901
- Acronym / sponsor ID
- TOLD / 20-192-2.F
- Conditions
- COVID-19 Pneumonia, Vascular Complications
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: reduction of Hospitalized COVID patients at UConnHealth
- Enrolment
- 41 participants (actual)
- Lead sponsor
- UConn HealthUniversity, hospital or other
- Study start
- 3 May 2020 (actual)
- Primary completion
- 22 Mar 2022 (actual)
- Study completion
- 24 Apr 2022 (actual)
- First posted
- 11 Jun 2020 (actual)
- Results
- Posted 21 Apr 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized Open Label Study Standard Care vs. Standard Care with Dipyridamole
| Arm | Type | Receives |
|---|---|---|
| Standard Care | Placebo comparator | Drug: PlaceboHospitalized 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. |
| Standard Care with Dipyridamole | Experimental | Drug: Dipyridamole TabletsFor 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Adults ≥18 years of age.
- 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
- o Fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms; shortness of breath with exertion
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboDaily dose while hospitalized up to 9 days | Drug | Standard Care |
| Dipyridamole TabletsAlso: PersantineDaily dose while hospitalized up to 9 days | Drug | Standard Care with Dipyridamole |
Primary outcome
D-dimer
Time frame: up to 9 days
Percent Change from Baseline [Day Zero] to last study measure (Day 3, Day 6 or Day 9)
Platelet Count
Time frame: up to 9 days
Percent Change from Baseline [Day Zero] to last study measure (Day 3, Day 6 or Day 9)
1 secondary outcome
Viral Detection
Time frame: 9 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bruce Liang, MD principal investigator
UConn Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dipyridamole Tablets in people with COVID-19 Pneumonia and Vascular Complications, run by UConn Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
D-dimer (time frame: up to 9 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2023.