Aggrenox To Treat Acute Covid-19

NCT04410328 | Completed Phase 3 Results DMC FDA Drug FDA Device

• 1 other identifier: Pro2020001469
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to explore the efficacy of Aggrenox in patients with SARS-CoV-2 infection with symptoms consistent with COVID-19. An anticipated total of 132 participants will be randomly divided almost equally into 2 groups: one group will receive Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally along with the standard of care and the other group with receive the standard of care only but no Dipyridamole ER 200mg/ Aspirin 25mg. Participants will be screened, enrolled, receive treatment, and followed for 28 days. The clinical and laboratory outcomes of all the participants enrolled in the study will be evaluated at the end of the study to explore if there is any difference in the outcomes between 2 groups.

Conditions

Covid19

Keywords

COVID-19; SARS-CoV; Aggrenox; Dipyridamole; Aspirin

Outcome Measures

Primary Outcomes (1)

• Covid (Coronavirus Disease-19) Ordinal Scale

  Change in composite COVID ordinal scale from day 1 to 14. Ordinal scale: 1) not hospitalized with resumption of normal activities; 2) not hospitalized, but unable to resume normal activities; 3) hospitalized, not requiring oxygen; 4) hospitalized, requiring oxygen; 5) hospitalized, requiring high-flow oxygen therapy, or noninvasive ventilation; 6) hospitalized, requiring invasive ventilation; 7) ventilation plus additional organ support such as pressors, renal replacement therapy and ECMO and 8) death. COVID Ordinal Scale ranges from 1 to 8, with score 1 on the scale corresponds to an ambulatory patient with minimal symptoms and score 8 on the scale corresponds to death.

  15 days

Secondary Outcomes (9)

• Mortality

  14 days

• Mortality

  28 days

• Inflammatory Marker Between Baseline and 7 Days

  Baseline and 7 days

• COVID Ordinal Scale

  28 days

• Number of Participants Not Requiring Supplemental Oxygen

  28 days

Study Arms (2)

Participants receiving Dipyridamole and Aspirin

EXPERIMENTAL

Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally plus standard care. Participants will receive Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally), 2 times daily starting on the day of enrollment for a total of 2 weeks.

Drug: Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally AND Standard of care; Other: Standard of care

Participants receiving standard of care

OTHER

Participants will receive standard care starting on the day of enrollment for a total of 2 weeks. Standard of care treatment consist of an intravenous Remidesivir 200 mg loading dose and then 100 mg/daily for a total of 4 days for non-intubated patients and 10 days for intubated patients, intravenous/oral decadron 6 mg/daily for 10 days and prophylactic subcutaneous LMWH daily, started on the day of enrollment and for the duration of hospitalization. If the patients are discharged before 10 days, they are prescribed oral decadron 6 mg daily to complete the course of 10 days.

Other: Standard of care

Interventions

Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally AND Standard of care DRUG

Participants in the experimental group will receive Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally (if they have a feeding tube), 2 times daily starting on the day of enrollment for a total of 2 weeks.

Also known as: Aggrenox

Participants receiving Dipyridamole and Aspirin

Standard of care OTHER

Participants will receive standard care starting on the day of enrollment for a total of 2 weeks. Standard of care treatment consist of an intravenous Remidesivir 200 mg loading dose and then 100 mg/daily for a total of 4 days for non-intubated patients and 10 days for intubated patients, intravenous/oral decadron 6 mg/daily for 10 days and prophylactic subcutaneous LMWH daily, started on the day of enrollment and for the duration of hospitalization. If the patients are discharged before 10 days, they are prescribed oral decadron 6 mg daily to complete the course of 10 days.

Participants receiving Dipyridamole and Aspirin; Participants receiving standard of care

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years.
• Hospitalization.
• SARS-CoV-2 viral nucleic acid positive within 3 days.
• Lab test result pending plus a high clinical suspicion for SARS-CoV-2 (fever and cough for ≤ 7 days, bilateral pulmonary infiltrates on imaging or new hypoxemia with spO2 ≤94% on room air or no alternative explanation for respiratory symptoms).
• Willing and able to provide consent or by authorized proxy.

You may not qualify if:

• Pregnancy.
• G-6PD deficiency.
• Use of antiplatelet agents including inhibitor of P2Y12 ADP platelet receptors, phosphodiesterase inhibitors, and Glycoprotein IIB/IIIA inhibitors.
• On therapeutic anticoagulation with coumadin, heparin and direct oral anticoagulants.
• Vasodilatory shock.
• Patient with known ongoing angina, recent myocardial infarction and sub-valvular aortic stenosis.
• Active gastric or duodenal ulcer or any bleeding disorder.
• Hemoglobin \<9 mg/dL, platelet count of \<30,000 /mm3.
• Acute respiratory infection for \>10 days.
• Known allergy/hypersensitivity to Dipyridamole and/or Aspirin.
• Severe hepatic or renal insufficiency.
• Uncontrolled hypertension defined as systolic \> 180 mm Hg or diastolic \> 100 mm Hg.
• Patients with known allergy to NSAIDs

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead
• Boehringer Ingelheim: collaborator

Study Sites (1)

Rutgers New Jersey Medical School University Hospital

Newark, New Jersey, 07103, United States

Location

Related Publications (6)

• Macatangay BJC, Jackson EK, Abebe KZ, Comer D, Cyktor J, Klamar-Blain C, Borowski L, Gillespie DG, Mellors JW, Rinaldo CR, Riddler SA. A Randomized, Placebo-Controlled, Pilot Clinical Trial of Dipyridamole to Decrease Human Immunodeficiency Virus-Associated Chronic Inflammation. J Infect Dis. 2020 Apr 27;221(10):1598-1606. doi: 10.1093/infdis/jiz344.

  PMID: 31282542 RESULT

• Li Z LX, Huang Yi-Y et al. FEP-based screening prompts drug repositioning against COVID-19. 2020.

  RESULT

• Liu X LZ, Liu S et al. . Therapeutic effects of dipyridamole on COVID-19 patients with coagulation dysfunction. 2020.

  RESULT

• Kohler D, Streienberger A, Morote-Garcia JC, Granja TF, Schneider M, Straub A, Boison D, Rosenberger P. Inhibition of Adenosine Kinase Attenuates Acute Lung Injury. Crit Care Med. 2016 Apr;44(4):e181-9. doi: 10.1097/CCM.0000000000001370.

  PMID: 26491864 RESULT

• Fata-Hartley CL, Palmenberg AC. Dipyridamole reversibly inhibits mengovirus RNA replication. J Virol. 2005 Sep;79(17):11062-70. doi: 10.1128/JVI.79.17.11062-11070.2005.

  PMID: 16103157 RESULT

• Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Li H, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Wang J, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, Wang C. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020 May 7;382(19):1787-1799. doi: 10.1056/NEJMoa2001282. Epub 2020 Mar 18.

  PMID: 32187464 RESULT

MeSH Terms

Conditions

COVID-19; Severe Acute Respiratory Syndrome

Interventions

Aspirin; Standard of Care; Aspirin, Dipyridamole Drug Combination

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Dipyridamole; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Amit Singla
• Organization: Rutgers New Jersey Medical School

as3321@njms.rutgers.edu

319-512-3558

Study Officials

• Amit Singla, MD

  Rutgers University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Arm 1: Aggrenox plus standard care. Participants will receive Aggrenox (Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally), 2 times daily (FDA-recommended dose) starting on the day of enrollment for a total of 2 weeks. Arm 2: Standard care. Participants will receive standard care starting on the day of enrollment for a total of 2 weeks. The investigators will perform a randomized, 2-arm, open-label single-site pilot study to evaluate the effect of oral Aggrenox (Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally), on clinical outcomes in patients with SARS-CoV-2. In this research proposal, the investigators will randomly assign 132 consenting participants with diagnosis of SARS-CoV-2 to two treatment groups: 1) Aggrenox (Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally) + standard care and 2) standard care alone. Participants will be screened, enrolled, receive treatment and followed for 28 days.

Study Record Dates

• First Submitted: May 28, 2020
• First Posted: June 1, 2020
• Study Start: October 21, 2020
• Primary Completion: October 15, 2021
• Study Completion: October 15, 2021
• Last Updated: February 21, 2025
• Results First Posted: February 21, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)