Back to resultsDipyridamole to Prevent Coronavirus Exacerbation of Respiratory Status (DICER) in COVID-19 (DICER)
Primary Purpose
COVID, Corona Virus Infection, Covid-19
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Dipyridamole 100 Milligram(mg)
Placebo oral tablet
Sponsored by
About this trial
This is an interventional treatment trial for COVID focused on measuring Oxygen
Eligibility Criteria
Inclusion Criteria:
- Willing and able to provide informed consent prior to performing study procedures unless they have a legally authorized representative (LAR)
- Confirmed coronavirus (SARS-CoV-2) infection
- Currently hospitalized or anticipated hospitalization requiring supplemental oxygen
Exclusion Criteria:
- In the opinion of at least two investigators, unlikely to survive for >48 hours from screening
- Concurrent enrollment in a clinical trial with a cytokine inhibitor (targeting interleukin-6 (IL-6), Interleukin-6 Receptor (IL-6R), IL-1, or Janus kinase). Use of remdesivir is permitted.
- Currently on invasive mechanical ventilation.
- Hypotension defined as systolic blood pressure < 90 mmHg on two sequential readings at least 4 hours apart
- Pregnant or breastfeeding
- Concurrent dual antithrombotic therapy (aspirin or P2Y12 inhibitor plus anticoagulation to treat deep venous thrombosis or pulmonary embolism (single antiplatelet or anticoagulant agent at prophylaxis or therapeutic dose is permitted)
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 5 times upper limit of normal, hemoglobin < 8 grams per deciliter (g/dL), or platelets <50,000 per cubic millimeter (mm3)
- History of recent major bleeding, defined in accordance with the criteria of the International Society on Thrombosis and Hemostasis (ISTH).
- Any physical examination findings and/or history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the patient by their participation in the study
Sites / Locations
- University of Michigan
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Dipyridamole 100 Milligram(mg)
Placebo
Arm Description
100 milligrams (mg) by mouth (PO) four times a day (QID)
Placebo given by mouth four times a day
Outcomes
Primary Outcome Measures
Percent Change in D-dimer
average percent daily change in plasma D-dimer levels compared to baseline
Number of Participants With Wins at Each Level of a Hierarchical Composite Rank Score
Compare each dipyridamole patient head to head against each placebo patient using a hierarchical composite rank score
death
days on mechanical ventilation
dichotomized (yes/no) decrease in daily average SpO2/FiO2 of at least 50 units relative to day 1 at anytime during the observation period
cumulative sum of COVID ordinal score during study hospitalization. Ordinal scores could range 1-8. Levels 1 and 2 imply no hospitalization and 8 is the worst possible score (death); by definition, the subjects in the DICER study were hospitalized during the time period in which the study observed their ordinal scores.
Secondary Outcome Measures
Days Alive and Free of Organ Support
Organ support is defined as receipt of invasive mechanical ventilation, vasopressor therapy, ECMO support, or dialysis.
Individual Component of Composite Endpoint- Death
Death of any cause during duration of study participation
Individual Component of Composite Endpoint- Days on Mechanical Ventilation
The number of days spent on invasive mechanical ventilation during study hospitalization.
Individual Component of Composite Endpoint- Sp02/Fi02 (as Shown by Participant Count)
Binary outcome indicating patients whose Sp02/Fi02 dropped 50 points relative to baseline at any time during hospitalization.
Individual Component of Composite Endpoint- Cumulative Ordinal Score
Cumulative sum of WHO Ordinal Scale for Clinical Improvement scores during hospitalization or through 14 days after study drug administration, whichever occurs first. The WHO Ordinal Scale ranges from 1 (no limitation of activities) through 8 (death). By definition, hospitalized patients score 3 or higher on the scale. The equation can be written: Cumulative Ordinal Score = (days in hospital up to 14) x (average ordinal score during hospitalization). Higher scores represent a combination of worse outcomes and longer hospitalizations.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04391179
Brief Title
Dipyridamole to Prevent Coronavirus Exacerbation of Respiratory Status (DICER) in COVID-19
Acronym
DICER
Official Title
Dipyridamole to Prevent Coronavirus Exacerbation of Respiratory Status (DICER) in COVID-19
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
May 31, 2020 (Actual)
Primary Completion Date
February 22, 2021 (Actual)
Study Completion Date
February 22, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Michigan
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The most severe manifestations of COVID-19 include respiratory failure, coagulation problems, and death. Inflammation and blood clotting are believed to play an important role in these manifestations. Research in humans has shown that dipyridamole can reduce blood clotting. This research study is being conducted to learn whether 14 days of treatment with dipyridamole will reduce excessive blood clotting in COVID-19.
This study will enroll participants with confirmed coronavirus (SARS-CoV)-2 infection that are admitted. Eligible participants will be randomized to receive dipyridamole or placebo for 14 days in the hospital. In addition, data will be collected from the medical record, and there will also be blood draws during the hospitalization.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID, Corona Virus Infection, Covid-19, SARS-CoV-2 Infection
Keywords
Oxygen
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
99 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dipyridamole 100 Milligram(mg)
Arm Type
Experimental
Arm Description
100 milligrams (mg) by mouth (PO) four times a day (QID)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo given by mouth four times a day
Intervention Type
Drug
Intervention Name(s)
Dipyridamole 100 Milligram(mg)
Intervention Description
Drug will be given for 14 days while in the hospital.
Intervention Type
Drug
Intervention Name(s)
Placebo oral tablet
Intervention Description
Placebo will be given for 14 days while in the hospital.
Primary Outcome Measure Information:
Title
Percent Change in D-dimer
Description
average percent daily change in plasma D-dimer levels compared to baseline
Time Frame
baseline, up to approximately 14 days after last study drug administration
Title
Number of Participants With Wins at Each Level of a Hierarchical Composite Rank Score
Description
Compare each dipyridamole patient head to head against each placebo patient using a hierarchical composite rank score
death
days on mechanical ventilation
dichotomized (yes/no) decrease in daily average SpO2/FiO2 of at least 50 units relative to day 1 at anytime during the observation period
cumulative sum of COVID ordinal score during study hospitalization. Ordinal scores could range 1-8. Levels 1 and 2 imply no hospitalization and 8 is the worst possible score (death); by definition, the subjects in the DICER study were hospitalized during the time period in which the study observed their ordinal scores.
Time Frame
up to approximately 30 days after hospital discharge
Secondary Outcome Measure Information:
Title
Days Alive and Free of Organ Support
Description
Organ support is defined as receipt of invasive mechanical ventilation, vasopressor therapy, ECMO support, or dialysis.
Time Frame
up to approximately 28 days after last study drug administration score
Title
Individual Component of Composite Endpoint- Death
Description
Death of any cause during duration of study participation
Time Frame
up to approximately 30 days after hospital discharge
Title
Individual Component of Composite Endpoint- Days on Mechanical Ventilation
Description
The number of days spent on invasive mechanical ventilation during study hospitalization.
Time Frame
up to 14 days after study drug administration
Title
Individual Component of Composite Endpoint- Sp02/Fi02 (as Shown by Participant Count)
Description
Binary outcome indicating patients whose Sp02/Fi02 dropped 50 points relative to baseline at any time during hospitalization.
Time Frame
up to 14 days after study drug administration
Title
Individual Component of Composite Endpoint- Cumulative Ordinal Score
Description
Cumulative sum of WHO Ordinal Scale for Clinical Improvement scores during hospitalization or through 14 days after study drug administration, whichever occurs first. The WHO Ordinal Scale ranges from 1 (no limitation of activities) through 8 (death). By definition, hospitalized patients score 3 or higher on the scale. The equation can be written: Cumulative Ordinal Score = (days in hospital up to 14) x (average ordinal score during hospitalization). Higher scores represent a combination of worse outcomes and longer hospitalizations.
Time Frame
Hospitalization up to 14 days after study drug administration
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Willing and able to provide informed consent prior to performing study procedures unless they have a legally authorized representative (LAR)
Confirmed coronavirus (SARS-CoV-2) infection
Currently hospitalized or anticipated hospitalization requiring supplemental oxygen
Exclusion Criteria:
In the opinion of at least two investigators, unlikely to survive for >48 hours from screening
Concurrent enrollment in a clinical trial with a cytokine inhibitor (targeting interleukin-6 (IL-6), Interleukin-6 Receptor (IL-6R), IL-1, or Janus kinase). Use of remdesivir is permitted.
Currently on invasive mechanical ventilation.
Hypotension defined as systolic blood pressure < 90 mmHg on two sequential readings at least 4 hours apart
Pregnant or breastfeeding
Concurrent dual antithrombotic therapy (aspirin or P2Y12 inhibitor plus anticoagulation to treat deep venous thrombosis or pulmonary embolism (single antiplatelet or anticoagulant agent at prophylaxis or therapeutic dose is permitted)
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 5 times upper limit of normal, hemoglobin < 8 grams per deciliter (g/dL), or platelets <50,000 per cubic millimeter (mm3)
History of recent major bleeding, defined in accordance with the criteria of the International Society on Thrombosis and Hemostasis (ISTH).
Any physical examination findings and/or history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the patient by their participation in the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jason Knight, MD, PhD
Organizational Affiliation
University of Michigan
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Dipyridamole to Prevent Coronavirus Exacerbation of Respiratory Status (DICER) in COVID-19
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