Trial Outcomes & Findings for Dipyridamole to Prevent Coronavirus Exacerbation of Respiratory Status (DICER) in COVID-19 (NCT NCT04391179)

NCT ID: NCT04391179

Last Updated: 2022-03-24

Results Overview

average percent daily change in plasma D-dimer levels compared to baseline

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 99 participants
• Primary outcome timeframe: baseline, up to approximately 14 days after last study drug administration
• Results posted on: 2022-03-24

Participant Flow

Between May 2020 and January 2021, 99 eligible participants received at least one dose of study drug and were included in the analysis.

Participant milestones

Measure	Dipyridamole 100 Milligram(mg) 100 milligrams (mg) by mouth (PO) four times a day (QID) Dipyridamole 100 Milligram(mg): Drug will be given for 14 days while in the hospital.	Placebo Placebo given by mouth four times a day Placebo oral tablet: Placebo will be given for 14 days while in the hospital.
Overall Study STARTED	49	50
Overall Study COMPLETED	34	34
Overall Study NOT COMPLETED	15	16

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Three patients did not have baseline D-Dimer values on the day of study drug.

Baseline characteristics by cohort

Measure	Dipyridamole 100 Milligram(mg) n=49 Participants 100 milligrams (mg) by mouth (PO) four times a day (QID) Dipyridamole 100 Milligram(mg): Drug will be given for 14 days while in the hospital.	Placebo n=50 Participants Placebo given by mouth four times a day Placebo oral tablet: Placebo will be given for 14 days while in the hospital.	Total n=99 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=49 Participants	0 Participants n=50 Participants	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	31 Participants n=49 Participants	29 Participants n=50 Participants	60 Participants n=99 Participants
Age, Categorical >=65 years	18 Participants n=49 Participants	21 Participants n=50 Participants	39 Participants n=99 Participants
Sex: Female, Male Female	16 Participants n=49 Participants	17 Participants n=50 Participants	33 Participants n=99 Participants
Sex: Female, Male Male	33 Participants n=49 Participants	33 Participants n=50 Participants	66 Participants n=99 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=49 Participants	1 Participants n=50 Participants	1 Participants n=99 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	46 Participants n=49 Participants	48 Participants n=50 Participants	94 Participants n=99 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=49 Participants	1 Participants n=50 Participants	4 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=49 Participants	0 Participants n=50 Participants	0 Participants n=99 Participants
Race (NIH/OMB) Asian	2 Participants n=49 Participants	3 Participants n=50 Participants	5 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=49 Participants	0 Participants n=50 Participants	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	2 Participants n=49 Participants	4 Participants n=50 Participants	6 Participants n=99 Participants
Race (NIH/OMB) White	45 Participants n=49 Participants	42 Participants n=50 Participants	87 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=49 Participants	1 Participants n=50 Participants	1 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=49 Participants	0 Participants n=50 Participants	0 Participants n=99 Participants
D-Dimer	1.06 mg/L STANDARD_DEVIATION .80 • n=47 Participants • Three patients did not have baseline D-Dimer values on the day of study drug.	1.24 mg/L STANDARD_DEVIATION 1.46 • n=49 Participants • Three patients did not have baseline D-Dimer values on the day of study drug.	1.15 mg/L STANDARD_DEVIATION 1.18 • n=96 Participants • Three patients did not have baseline D-Dimer values on the day of study drug.
Oxygen Saturation (SpO2)/Fraction of Inspired Oxygen (FiO2)	308 ratio STANDARD_DEVIATION 70 • n=49 Participants	310 ratio STANDARD_DEVIATION 72 • n=50 Participants	309 ratio STANDARD_DEVIATION 71 • n=99 Participants

PRIMARY outcome

Timeframe: baseline, up to approximately 14 days after last study drug administration

average percent daily change in plasma D-dimer levels compared to baseline

Outcome measures

Measure	Dipyridamole 100 Milligram(mg) n=49 Participants 100 milligrams (mg) by mouth (PO) four times a day (QID) Dipyridamole 100 Milligram(mg): Drug will be given for 14 days while in the hospital.	Placebo n=50 Participants Placebo given by mouth four times a day Placebo oral tablet: Placebo will be given for 14 days while in the hospital.
Percent Change in D-dimer	-5.6 percent daily change Interval -10.2 to -0.07	-2.4 percent daily change Interval -6.9 to 2.3

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Dipyridamole 100 Milligram(mg) n=49 Participants 100 milligrams (mg) by mouth (PO) four times a day (QID) Dipyridamole 100 Milligram(mg): Drug will be given for 14 days while in the hospital.	Placebo n=50 Participants Placebo given by mouth four times a day Placebo oral tablet: Placebo will be given for 14 days while in the hospital.
Number of Participants With Wins at Each Level of a Hierarchical Composite Rank Score Composite endpoint- death	0 Participants	3 Participants
Number of Participants With Wins at Each Level of a Hierarchical Composite Rank Score Composite endpoint- mechanical ventilation during hospitalization	3 Participants	4 Participants
Number of Participants With Wins at Each Level of a Hierarchical Composite Rank Score Composite endpoint- 50+ unit drop SpO2/FiO2	13 Participants	11 Participants
Number of Participants With Wins at Each Level of a Hierarchical Composite Rank Score Composite endpoint- remaining (ties among patients evaluated by ordinal score)	33 Participants	32 Participants

SECONDARY outcome

Timeframe: up to approximately 28 days after last study drug administration score

Population: 5 participants on dipyridamole and 2 participants on placebo were excluded from this analysis because of their early withdrawal from the study (prior to 28 days after last study drug administration).

Organ support is defined as receipt of invasive mechanical ventilation, vasopressor therapy, ECMO support, or dialysis.

Outcome measures

Measure	Dipyridamole 100 Milligram(mg) n=44 Participants 100 milligrams (mg) by mouth (PO) four times a day (QID) Dipyridamole 100 Milligram(mg): Drug will be given for 14 days while in the hospital.	Placebo n=48 Participants Placebo given by mouth four times a day Placebo oral tablet: Placebo will be given for 14 days while in the hospital.
Days Alive and Free of Organ Support	28 days Interval 28.0 to 28.0	28 days Interval 28.0 to 28.0

SECONDARY outcome

Timeframe: up to approximately 30 days after hospital discharge

Death of any cause during duration of study participation

Outcome measures

Measure	Dipyridamole 100 Milligram(mg) n=49 Participants 100 milligrams (mg) by mouth (PO) four times a day (QID) Dipyridamole 100 Milligram(mg): Drug will be given for 14 days while in the hospital.	Placebo n=50 Participants Placebo given by mouth four times a day Placebo oral tablet: Placebo will be given for 14 days while in the hospital.
Individual Component of Composite Endpoint- Death	0 Participants	3 Participants

SECONDARY outcome

Timeframe: up to 14 days after study drug administration

The number of days spent on invasive mechanical ventilation during study hospitalization.

Outcome measures

Measure	Dipyridamole 100 Milligram(mg) n=49 Participants 100 milligrams (mg) by mouth (PO) four times a day (QID) Dipyridamole 100 Milligram(mg): Drug will be given for 14 days while in the hospital.	Placebo n=50 Participants Placebo given by mouth four times a day Placebo oral tablet: Placebo will be given for 14 days while in the hospital.
Individual Component of Composite Endpoint- Days on Mechanical Ventilation	0.33 days Standard Deviation 1.36	0.88 days Standard Deviation 2.74

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Dipyridamole 100 Milligram(mg) n=49 Participants 100 milligrams (mg) by mouth (PO) four times a day (QID) Dipyridamole 100 Milligram(mg): Drug will be given for 14 days while in the hospital.	Placebo n=50 Participants Placebo given by mouth four times a day Placebo oral tablet: Placebo will be given for 14 days while in the hospital.
Individual Component of Composite Endpoint- Sp02/Fi02 (as Shown by Participant Count)	14 Participants	14 Participants

SECONDARY outcome

Timeframe: Hospitalization up to 14 days after study drug administration

Population: excluded patients that died or withdrew from the study

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.

Outcome measures

Measure	Dipyridamole 100 Milligram(mg) n=44 Participants 100 milligrams (mg) by mouth (PO) four times a day (QID) Dipyridamole 100 Milligram(mg): Drug will be given for 14 days while in the hospital.	Placebo n=48 Participants Placebo given by mouth four times a day Placebo oral tablet: Placebo will be given for 14 days while in the hospital.
Individual Component of Composite Endpoint- Cumulative Ordinal Score	14.3 score on a scale * days Interval 9.4 to 21.4	15.0 score on a scale * days Interval 7.8 to 30.0

Adverse Events

Dipyridamole 100 Milligram(mg)

Serious events: 14 serious events

Other events: 43 other events

Deaths: 0 deaths

Placebo

Serious events: 30 serious events

Other events: 15 other events

Deaths: 3 deaths

Serious adverse events

Measure	Dipyridamole 100 Milligram(mg) n=49 participants at risk 100 milligrams (mg) by mouth (PO) four times a day (QID) Dipyridamole 100 Milligram(mg): Drug will be given for 14 days while in the hospital.	Placebo n=50 participants at risk Placebo given by mouth four times a day Placebo oral tablet: Placebo will be given for 14 days while in the hospital.
Cardiac disorders Atrial Fibrillation	0.00% 0/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	2.0% 1/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Psychiatric disorders Delirium	2.0% 1/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	0.00% 0/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory failure	14.3% 7/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	28.0% 14/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Vascular disorders Hypotension	2.0% 1/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	4.0% 2/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Cardiac disorders Heart failure	2.0% 1/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	0.00% 0/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Lung infection	4.1% 2/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	14.0% 7/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary edema	2.0% 1/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	0.00% 0/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Vascular disorders Thromboembolic event	2.0% 1/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	2.0% 1/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Cardiac disorders Cardiac Arrest	0.00% 0/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	2.0% 1/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Cardiac disorders Myocardial infarction	0.00% 0/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	2.0% 1/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Cardiac disorders Paroxysmal artrial tachycardia	0.00% 0/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	2.0% 1/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Musculoskeletal and connective tissue disorders Pneumothorax	0.00% 0/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	2.0% 1/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Cardiac disorders Stroke	0.00% 0/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	2.0% 1/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.

Other adverse events

Measure	Dipyridamole 100 Milligram(mg) n=49 participants at risk 100 milligrams (mg) by mouth (PO) four times a day (QID) Dipyridamole 100 Milligram(mg): Drug will be given for 14 days while in the hospital.	Placebo n=50 participants at risk Placebo given by mouth four times a day Placebo oral tablet: Placebo will be given for 14 days while in the hospital.
Nervous system disorders Headache	34.7% 17/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	6.0% 3/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	6.1% 3/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	0.00% 0/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
General disorders Delirium	4.1% 2/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	2.0% 1/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
General disorders Abdominal pain	4.1% 2/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	0.00% 0/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Psychiatric disorders Anxiety	4.1% 2/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	0.00% 0/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Vascular disorders Epistaxis	4.1% 2/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	0.00% 0/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Nervous system disorders Paresthesia	2.0% 1/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	2.0% 1/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Cardiac disorders Bradycardia	0.00% 0/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	2.0% 1/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Cardiac disorders Heart failure	0.00% 0/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	2.0% 1/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Cardiac disorders Ventricular arrhythmia	0.00% 0/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	2.0% 1/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Cardiac disorders Electrocardiogram QT corrected interval prolonged	0.00% 0/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	2.0% 1/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Cardiac disorders Palpitations	2.0% 1/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	0.00% 0/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Renal and urinary disorders Edema limbs	0.00% 0/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	2.0% 1/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Renal and urinary disorders Acute kidney injury	2.0% 1/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	0.00% 0/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Renal and urinary disorders Kidney infection	2.0% 1/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	0.00% 0/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Renal and urinary disorders Atypical urothelial cells in urine	2.0% 1/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	0.00% 0/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Renal and urinary disorders Incontinence	2.0% 1/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	0.00% 0/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Gastrointestinal disorders Diarrhea	2.0% 1/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	0.00% 0/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Gastrointestinal disorders Emesis	2.0% 1/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	0.00% 0/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Gastrointestinal disorders Aspartate aminotransferase increased	0.00% 0/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	2.0% 1/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Vascular disorders Vaginal hemorrhage	0.00% 0/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	2.0% 1/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Vascular disorders Hypotension	2.0% 1/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	0.00% 0/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	2.0% 1/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Skin and subcutaneous tissue disorders Rash maculo-papular	2.0% 1/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	0.00% 0/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Musculoskeletal and connective tissue disorders Neck pain	2.0% 1/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	0.00% 0/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
Musculoskeletal and connective tissue disorders Ankle pain	2.0% 1/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	0.00% 0/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
General disorders Body pain	0.00% 0/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	2.0% 1/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
General disorders Fall	0.00% 0/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	2.0% 1/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
General disorders Non-cardiac chest pain	2.0% 1/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	0.00% 0/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
General disorders Diaphoresis	2.0% 1/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	0.00% 0/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.
General disorders Tremor	2.0% 1/49 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.	0.00% 0/50 • The collection period for adverse events began after informed consent and ended 30 days after administration of the last dose of study drug.

Additional Information

Jason Knight, MD, PhD

University of Michigan

Phone: 734-763-3031

Email: jsknight@med.umich.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place