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

• ClinicalTrials.gov Identifier: NCT04391179
• Recruitment Status: Completed
• First Posted: May 18, 2020
• Results First Posted: March 24, 2022
• Last Update Posted: March 24, 2022
• Sponsor: University of Michigan
• Information provided by (Responsible Party): Jason Scott Knight, University of Michigan

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.

Condition or disease	Intervention/treatment	Phase
COVID; Corona Virus Infection; Covid-19; SARS-CoV-2 Infection	Drug: Dipyridamole 100 Milligram(mg); Drug: Placebo oral tablet	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 99 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Dipyridamole to Prevent Coronavirus Exacerbation of Respiratory Status (DICER) in COVID-19
• Actual Study Start Date: May 31, 2020
• Actual Primary Completion Date: February 22, 2021
• Actual Study Completion Date: February 22, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dipyridamole 100 Milligram(mg); 100 milligrams (mg) by mouth (PO) four times a day (QID)	Drug: Dipyridamole 100 Milligram(mg); Drug will be given for 14 days while in the hospital.
Placebo Comparator: Placebo; Placebo given by mouth four times a day	Drug: Placebo oral tablet; Placebo will be given for 14 days while in the hospital.

Outcome Measures

Primary Outcome Measures :

1. Percent Change in D-dimer [ Time Frame: baseline, up to approximately 14 days after last study drug administration ]
   average percent daily change in plasma D-dimer levels compared to baseline
2. Number of Participants With Wins at Each Level of a Hierarchical Composite Rank Score [ Time Frame: 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.

Secondary Outcome Measures :

1. Days Alive and Free of Organ Support [ Time Frame: 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.
2. Individual Component of Composite Endpoint- Death [ Time Frame: up to approximately 30 days after hospital discharge ]
   Death of any cause during duration of study participation
3. Individual Component of Composite Endpoint- Days on Mechanical Ventilation [ Time Frame: up to 14 days after study drug administration ]
   The number of days spent on invasive mechanical ventilation during study hospitalization.
4. Individual Component of Composite Endpoint- Sp02/Fi02 (as Shown by Participant Count) [ Time Frame: 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.
5. Individual Component of Composite Endpoint- Cumulative Ordinal Score [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

Sponsors and Collaborators

University of Michigan

Investigators

• Principal Investigator: Jason Knight, MD, PhD; University of Michigan

  Study Documents (Full-Text)

Documents provided by Jason Scott Knight, University of Michigan:

Study Protocol  [PDF] July 12, 2021

Statistical Analysis Plan  [PDF] February 3, 2022

More Information

• Responsible Party: Jason Scott Knight, Associate Professor of Internal Medicine, University of Michigan
• ClinicalTrials.gov Identifier: NCT04391179
• Other Study ID Numbers: HUM00179783
• First Posted: May 18, 2020
• Results First Posted: March 24, 2022
• Last Update Posted: March 24, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jason Scott Knight, University of Michigan:

Oxygen

Additional relevant MeSH terms:

COVID-19; Dipyridamole; Infections; Communicable Diseases; Coronavirus Infections; Disease Attributes; Pathologic Processes; Respiratory Tract Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Phosphodiesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Vasodilator Agents