Treat COVID-19 Patients With Regadenoson

NCT04606069 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: HP-00091372
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

More than 17 million people have been infected and more than 677K lives have been lost since the COVID-19 pandemic. Unfortunately, there is neither an effective treatment nor is there a vaccination for this deadly virus. The moderate to severe COVID-19 patients suffer acute lung injury and need oxygen therapy, and even ventilators, to help them breathe. When a person gets a viral infection, certain body cells (inflammatory/immune cells) get activated and release a wide range of small molecules, also known as cytokines, to help combat the virus. But it is possible for the body to overreact to the virus and release an overabundance of cytokines, forming what is known as a "cytokine storm". When a cytokine storm is formed, these cytokines cause more damage to their own cells than to the invading COVID-19 that they're trying to fight. Recently, doctors and research scientists are becoming increasingly convinced that, in some cases, this is likely what is happening in the moderate to severe COVID-19 patients. The cytokine storm may be contributing to respiratory failure, which is the leading cause of mortality for severe COVID-19 patients. Therefore, being able to control the formation of cytokine storms will also help alleviate the symptoms and aid in the recovery of severe COVID-19 patients.

Conditions

COVID-19; Lung Inflammation

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients Alive and Free of Respiratory Failure Through the 30-day Trial.

  Respiratory failure is defined based on resource utilization requiring at least 1 of the following modalities: 1. Endotracheal intubation and mechanical ventilation 2. Oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates \>20L/min with fraction of delivered oxygen ≥0.5) 3. Noninvasive positive pressure ventilation or CPAP 4. Whether patient is on ECMO

  30 Days

Secondary Outcomes (1)

• Change of the Levels of the Inflammatory Cytokines Prior, During and Post Drug Infusion.

  Baseline, 30mins into infusion, 4 hours into drug infusion and 24 hours post drug infusion

Study Arms (2)

Active Arm

EXPERIMENTAL

Regadenoson will be given intravenously as 5 ug/kg loading dose (up to 400 mg/patient) over 30 mins (to avoid unpleasant side effects sometimes associated with the rapid bolus injection of Regadenoson), followed by a continuous slow infusion (1.44micrograms/kg/hour) with the use of a pediatric infusion pump for 6 hours.

Drug: Regadenoson

Control Arm

PLACEBO COMPARATOR

The same volume of saline will be given intravenously for 30 mins followed by a continuous infusion for 6 hours.

Other: Placebo Control

Interventions

Regadenoson DRUG

Regadenoson will be given intravenously as 5 ug/kg (up to 400 mg/patient) loading dose over 30 mins (to avoid unpleasant side effects sometimes associated with the rapid bolus injection of Regadenoson), followed by a continuous slow infusion (1.44micrograms/kg/hour) with the use of a pediatric infusion pump for 6 hours.

Also known as: LEXISCAN,

Active Arm

Placebo Control OTHER

The same volume of saline will be given intravenously for 6 and half hours.

Also known as: Saline

Control Arm

Eligibility Criteria

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

You may qualify if:

• Age: adults 18 years and older
• Laboratory-confirmed COVID-19+ by RT-PCR
• Moderate to Severe COVID-19 patients according to FDA's COVID-19 treatment guideline on Management of Persons with COVID-19: Moderate illness is defined as individuals who have evidence of lower respiratory disease by clinical assessment or imaging and a saturation of oxygen (SpO2) \>93% on room air at sea level. Severe Illness is defined as individuals who have respiratory frequency \>30 breaths per minute, SpO2 ≤ 93% on room air at sea level, ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) \<300, or lung infiltrates \>50%
• Written informed consent must be obtained before any study procedure is performed.

You may not qualify if:

• Pregnant or breastfeeding women
• Symptoms or signs of acute myocardial ischemia
• Sinoatrial (SA) and Atrioventricular (AV) Nodal Block/dysfunction
• Symptoms or signs of Atrial Fibrillation/Atrial Flutter
• History of Hypotension
• History of severe hypertension not adequately controlled with anti-hypertensive medications (Systolic blood pressure ≥ 200 mmHg and/or Diastolic blood pressure ≥ 110 mmHg)
• Severe renal impairment defined as glomerular filtration rate (GFR) \< 30 ml/min
• History of clinically overt stroke within the past 3 years
• History of seizure disorder
• Pre-existing asthma or chronic obstructive pulmonary disease
• Chronic anti-coagulation or anti-platelet therapy that would preclude surgery (prophylactic aspirin is acceptable)
• Treatment within 30 days with Hydroxychloroquine (HCQ) or Azithromycin
• Treatment with Janus Kinase inhibitors
• Treatment with theophylline or aminophylline within 12 hours of study dosing
• Treatment with Persantine and/or Aggrenox within 5 days

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Related Publications (4)

• Lau CL, Beller JP, Boys JA, Zhao Y, Phillips J, Cosner M, Conaway MR, Petroni G, Charles EJ, Mehaffey JH, Mannem HC, Kron IL, Krupnick AS, Linden J. Adenosine A2A receptor agonist (regadenoson) in human lung transplantation. J Heart Lung Transplant. 2020 Jun;39(6):563-570. doi: 10.1016/j.healun.2020.02.003. Epub 2020 Feb 13.

  PMID: 32503727 BACKGROUND

• Field JJ, Majerus E, Gordeuk VR, Gowhari M, Hoppe C, Heeney MM, Achebe M, George A, Chu H, Sheehan B, Puligandla M, Neuberg D, Lin G, Linden J, Nathan DG. Randomized phase 2 trial of regadenoson for treatment of acute vaso-occlusive crises in sickle cell disease. Blood Adv. 2017 Aug 28;1(20):1645-1649. doi: 10.1182/bloodadvances.2017009613. eCollection 2017 Sep 12.

  PMID: 29296811 BACKGROUND

• Zhao Y, Xiao A, diPierro CG, Carpenter JE, Abdel-Fattah R, Redpath GT, Lopes MB, Hussaini IM. An extensive invasive intracranial human glioblastoma xenograft model: role of high level matrix metalloproteinase 9. Am J Pathol. 2010 Jun;176(6):3032-49. doi: 10.2353/ajpath.2010.090571. Epub 2010 Apr 22.

  PMID: 20413683 BACKGROUND

• Zhao Y, Sharma AK, LaPar DJ, Kron IL, Ailawadi G, Liu Y, Jones DR, Laubach VE, Lau CL. Depletion of tissue plasminogen activator attenuates lung ischemia-reperfusion injury via inhibition of neutrophil extravasation. Am J Physiol Lung Cell Mol Physiol. 2011 May;300(5):L718-29. doi: 10.1152/ajplung.00227.2010. Epub 2011 Mar 4.

  PMID: 21378024 BACKGROUND

MeSH Terms

Conditions

COVID-19; Pneumonia

Interventions

regadenoson; Sodium Chloride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

This study did not include untreated patient controls or have sufficient power to determine if RA reduced mortality or length of stay in the hospital.

Results Point of Contact

• Title: Dr. Christine Lau, MD, MBA, Department of Surgery, Surgeon-in-Chief
• Organization: University of Maryland Medical Center

CLLau@som.umaryland.edu

410-328-8407

Study Officials

• Christine L Lau, MD, MBA

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Robert W. Buxton Professor and Chair Department of Surgery

Study Record Dates

• First Submitted: October 26, 2020
• First Posted: October 28, 2020
• Study Start: May 6, 2021
• Primary Completion: April 24, 2023
• Study Completion: April 24, 2023
• Last Updated: March 20, 2025
• Results First Posted: March 20, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)