Treat COVID-19 Patients With Regadenoson
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|ClinicalTrials.gov Identifier: NCT04606069|
Recruitment Status : Not yet recruiting
First Posted : October 28, 2020
Last Update Posted : October 28, 2020
|Condition or disease||Intervention/treatment||Phase|
|COVID-19 Lung Inflammation||Drug: Regadenoson Other: Placebo Control||Phase 1 Phase 2|
The investigators reason that Regadenoson treatment will reduce COVID-19-induced lung injury by inhibiting hyperinflammation. Our overarching goal is to demonstrate that Regadenoson treatment increases survival by reducing hyperinflammation and pulmonary function. The investigators will test the hypothesis that Regadenoson elicits clinical improvement and enhances survival compared to placebo control patients with COVID-19. The investigators hypothesize that the survival benefit of Regadenoson will be additive or synergistic with the anti-viral drug, Remdesivir. Remdesivir and Dexamethasone are currently standard of care and would remain so.
Specific Aim 1: will determine the initial high dose followed by low dose continuous infusion that is safe and feasible in moderate to severe COVID-19 patients. Even if the dosages that the investigators will use in moderate to severe COVID-19 patients has been proved to be safe in myocardial perfusion imaging patients, sickle cells disease and lung transplantation patients, it is still unclear whether it is safe in COVID-19 patients. Therefore, our primary endpoint for this Aim will be safety. For the first 6 patients, the investigators will be looking at any drug related side effects and toxicity of Regadenoson as the investigators did in lung transplantation trial.
Specific Aim 2: will determine the potential efficacy of Regadenoson infusion in moderate to severe COVID-19 patients. If Regadenoson infusion is safe and feasible in the moderate to severe COVID-19 patients in Aim 1, the investigators will test its efficacy in 34 moderate to severe COVID-19 patients in a randomized controlled trial of regadenoson versus placebo control. The primary endpoints of this specific aim are: 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, 2) Endotracheal intubation and mechanical ventilation, 3) 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), 4) Noninvasive positive pressure ventilation or CPAP, 5) ECMO.
Specific Aim 3: will explore the mechanisms of the effects of Regadenoson infusion in moderate to severe COVID-19 patients. If Regadenoson is proved to be effective on treating moderate to severe COVID-19 patients in Aim 2, the investigators will continue the study in this Aim. The investigators will measure 1) the plasma levels of Regadenoson in the collected blood samples (these will be done only on the first 6 patients as the investigators need specific time points and want to limit non routine blood draws); 2) the levels of pro-inflammatory cytokines (TNF-α, IL-1, IL-6, IL-12, IL-8, INF-γ, etc) and anti-inflammatory cytokines ( IL-4 and IL-10), and 3) the levels of matrix metalloproteinase-9 (MM-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in blood samples which will be collected from COVID-19 patients at prior baseline lab draws and also next day am routine labs. For the first 6-patients the investigators will ask for 2- additional study lab draws, one at the conclusion of the 30-min infusion and one at 4-hours into the 6-hours slow continuous infusion. The investigators may limit this to 3 if there are no dose limiting toxicities. The investigators are asking for up to 6 in the safety aim 1 in case one of the 3 has a dose limiting toxicity the investigators would then provide to 6 total. 5 of 6 would need to be without dose limiting toxicity to continue with the additional 34 patients.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||Clinical Trial on the Safety and Efficacy of Regadenoson for Moderate to Severe COVID-19 Adult Patients|
|Estimated Study Start Date :||November 1, 2020|
|Estimated Primary Completion Date :||November 30, 2021|
|Estimated Study Completion Date :||January 31, 2022|
Experimental: Active Arm
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.
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.
Other Name: LEXISCAN,
Placebo Comparator: Control Arm
The same volume of saline will be given intravenously for 30 mins followed by a continuous infusion for 6 hours.
Other: Placebo Control
The same volume of saline will be given intravenously for 6 and half hours.
Other Name: Saline
- Proportion of patients alive and free of respiratory failure through the 30-day trial. [ Time Frame: 30 Days ]
Respiratory failure is defined based on resource utilization requiring at least 1 of the following modalities:
- Endotracheal intubation and mechanical ventilation
- 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)
- Noninvasive positive pressure ventilation or CPAP
- Whether patient is on ECMO
- Change of the levels of the inflammatory cytokines prior, during and post drug infusion. [ Time Frame: 30 days ]We will collect blood samples of the regadenoson and placebo treated patients at the baseline, 30mins, 4 hours during drug infusion and 12 hour post drug infusion. It may also including the daily blood collected on normal standard care base. The inflammatory cytokines, including IL-1 beta, IL-6, IL-4, IL-8, IL-10, IL-12, IL-17, TNF-α, and IFN-γ will be measured using the Luminex™ 100 Multi-analyte System at The UM SOM Cytokine Core Laboratory. The levels of of cytokines will be measure in picogram/milliliter (pg/ml).
- Change of the levels of MMP-2 and MMP-9 prior, during and post drug infusion. [ Time Frame: 30 days ]The same blood samples used in outcomes 2 will be used to measure the levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 using gelatin zymography as described in our previous publications (Zhao et al, 2010 & 2011). The enzyme levels will be quantified using The Image Lab 5.1 software. The unit will be nanogram/ml (ng/ml).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04606069
|Contact: Melissa Culligan, RNemail@example.com|
|Contact: Manal Al-Suqi, MSTC||410-328-9409||MaAl-Suqi@som.umaryland.edu|
|Principal Investigator:||Christine L Lau, MD, MBA||University of Maryland, Baltimore|