Dipyridamole to Prevent Coronavirus Exacerbation of Respiratory Status (DICER) in COVID-19

Phase 2

Completed

• Conditions: COVID; Covid-19; Corona Virus Infection; SARS-CoV-2 Infection
• Interventions: Drug: Dipyridamole 100 Milligram(mg); Drug: Placebo oral tablet

• Registration Number: NCT04391179
• Lead Sponsor: University of Michigan

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2020-05-15
• Study First Submitted QC: 2020-05-15
• Study First Posted: 2020-05-18
• Study Start: 2020-05-31
• Primary Completion: 2021-02-22
• Study Completion: 2021-02-22
• Status Verified: 2022-03
• Results First Submitted: 2022-03-04
• Results First Submitted QC: 2022-03-18
• Last Update Submitted: 2022-03-18
• Results First Posted: 2022-03-24
• Last Update Posted: 2022-03-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 99

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dipyridamole 100 Milligram(mg)	Dipyridamole 100 Milligram(mg)	100 milligrams (mg) by mouth (PO) four times a day (QID)
Placebo	Placebo oral tablet	Placebo given by mouth four times a day

Primary Outcome Measures

Name	Time	Method
Number of Participants With Wins at Each Level of a Hierarchical Composite Rank Score	up to approximately 30 days after hospital discharge	Compare each dipyridamole patient head to head against each placebo patient using a hierarchical composite rank score; 1. death; 2. days on mechanical ventilation; 3. dichotomized (yes/no) decrease in daily average SpO2/FiO2 of at least 50 units relative to day 1 at anytime during the observation period; 4. 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.
Percent Change in D-dimer	baseline, up to approximately 14 days after last study drug administration	average percent daily change in plasma D-dimer levels compared to baseline

Secondary Outcome Measures

Name	Time	Method
Days Alive and Free of Organ Support	up to approximately 28 days after last study drug administration score	Organ support is defined as receipt of invasive mechanical ventilation, vasopressor therapy, ECMO support, or dialysis.
Individual Component of Composite Endpoint- Days on Mechanical Ventilation	up to 14 days after study drug administration	The number of days spent on invasive mechanical ventilation during study hospitalization.
Individual Component of Composite Endpoint- Cumulative Ordinal Score	Hospitalization up to 14 days after study drug administration	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.
Individual Component of Composite Endpoint- Death	up to approximately 30 days after hospital discharge	Death of any cause during duration of study participation
Individual Component of Composite Endpoint- Sp02/Fi02 (as Shown by Participant Count)	up to 14 days after study drug administration	Binary outcome indicating patients whose Sp02/Fi02 dropped 50 points relative to baseline at any time during hospitalization.

Trial Locations

Locations (1)

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States