Regadenoson 400micrograms/5ml solution for injection vials

Objective: We hypothesized that regadenoson, an adenosine A2A receptor agonist, will increase the use rate after ex vivo lung perfusion and reduce ischemic reperfusion injury. Methods: This randomized (2:1), multicenter, blinded, placebo-controlled trial (NCT04521569) treated donor lungs with a regadenoson infusion (1.44 μg/kg/h, n = 26) or placebo (n = 8) during ex vivo lung perfusion. Eligibility criteria were adapted from the NOVEL trial. The rate of use of donor lungs was the primary end point. Secondary end points were primary graft dysfunction scores and 30-day safety. Results: .87). No adverse events were related to the study treatment. Conclusions: There was no significant increase in the use of marginal donor lungs or a decrease in ischemic reperfusion injury in lungs undergoing ex vivo lung perfusion with regadenoson compared with placebo. Regadenoson is a safe ex vivo lung perfusion adjunct. The use rate of the placebo group was greater than the expectation set in the NOVEL trial of 51%, making it difficult for the regadenoson group to have a significant increase in use.

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Sickle cell disease (SCD) is a genetic disorder characterized by rigid, sickle-shaped red blood cells, leading to complications such as vaso-occlusive crises (VOCs). These acute pain episodes are the most common reason for emergency visits and hospitalizations in adults with SCD. his narrative review evaluated the efficacy of pharmacological and non-pharmacological treatments for acute pain crises in adults with SCD, with secondary attention to safety outcomes, including side effects, treatment duration, hospital stay, and readmission rates. Materials and Methods: A literature search was conducted in PubMed, Cochrane Library, and Google Scholar up to August 20, 2024, focusing on randomized controlled trials (RCTs) in English involving adult patients. Relevant studies were reviewed, and findings were synthesized narratively. The result Twelve RCTs involving 576 adults were included. Most studies were of good quality, though two had high risk and two had unclear risk of bias. Interventions included L-glutamine, pregabalin, regadenoson, ketorolac, individualized opioid protocols, progressive muscle relaxation, and music therapy. L-glutamine and individualized opioid protocols consistently reduced pain intensity. Pregabalin and ketorolac showed mixed results, while non-pharmacological interventions provided modest pain relief or improved mood. Overall, individualized treatment approaches appeared more effective than uniform protocols, though variability in study design and outcomes limits generalizability. IIn conclusion Twelve RCTs involving 576 adults were included. Most studies were of good quality, though two had high risk and two had unclear risk of bias. Interventions included L-glutamine, pregabalin, regadenoson, ketorolac, individualized opioid protocols, progressive muscle relaxation, and music therapy. L-glutamine and individualized opioid protocols consistently reduced pain intensity. Pregabalin and ketorolac showed mixed results, while non-pharmacological interventions provided modest pain relief or improved mood. Overall, individualized treatment approaches appeared more effective than uniform protocols, though variability in study design and outcomes limits generalizability. TEK therapy and L-glutamine were most effective for pain reduction, while pregabalin and regadenoson were safe and promising. Non-pharmacological interventions may support standard care, but further high-quality RCTs are recommended to confirm efficacy and safety.

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BACKGROUND: Adenosine inhibits the activation of most immune cells and platelets. Selective adenosine A2A receptor (A2AR) agonists such as regadenoson (RA) reduce inflammation in most tissues, including lungs injured by hypoxia, ischemia, transplantation, or sickle cell anemia, principally by suppressing the activation of invariant natural killer T (iNKT) cells. The anti-inflammatory effects of RA are magnified in injured tissues due to induction in immune cells of A2ARs and ecto-enzymes CD39 and CD73 that convert ATP to adenosine in the extracellular space. Here we describe the results of a five patient study designed to evaluate RA safety and to seek evidence of reduced cytokine storm in hospitalized COVID-19 patients. METHODS AND FINDINGS: Five COVID-19 patients requiring supplemental oxygen but not intubation (WHO stages 4-5) were infused IV with a loading RA dose of 5 μg/kg/h for 0.5 h followed by a maintenance dose of 1.44 μg/kg/h for 6 hours, Vital signs and arterial oxygen saturation were recorded, and blood samples were collected before, during and after RA infusion for analysis of CRP, D-dimer, circulating iNKT cell activation state and plasma levels of 13 proinflammatory cytokines. RA was devoid of serious side effects, and within 24 hours from the start of infusion was associated with increased oxygen saturation (93.8 ± 0.58 vs 96.6 ± 1.08%, P<0.05), decreased D-dimer (754 ± 17 vs 518 ± 98 ng/ml, P<0.05), and a trend toward decreased CRP (3.80 ± 1.40 vs 1.98 ± 0.74 mg/dL, P = 0.075). Circulating iNKT cells, but not conventional T cells, were highly activated in COVID-19 patients (65% vs 5% CD69+). RA infusion for 30 minutes reduced iNKT cell activation by 50% (P<0.01). RA infusion for 30 minutes did not influence plasma cytokines, but infusion for 4.5 or 24 hours reduced levels of 11 of 13 proinflammatory cytokines. In separate mouse studies, subcutaneous RA infusion from Alzet minipumps at 1.44 μg/kg/h increased 10-day survival of SARS-CoV-2-infected K18-hACE2 mice from 10 to 40% (P<0.001). CONCLUSIONS: Infused RA is safe and produces rapid anti-inflammatory effects mediated by A2A adenosine receptors on iNKT cells and possibly in part by A2ARs on other immune cells and platelets. We speculate that iNKT cells are activated by release of injury-induced glycolipid antigens and/or alarmins such as IL-33 derived from virally infected type II epithelial cells which in turn activate iNKT cells and secondarily other immune cells. Adenosine released from hypoxic tissues, or RA infused as an anti-inflammatory agent decrease proinflammatory cytokines and may be useful for treating cytokine storm in patients with Covid-19 or other inflammatory lung diseases or trauma.

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Background/Objectives: Regadenoson, a selective adenosine A2A receptor agonist, is primarily prescribed for myocardial perfusion imaging (MPI). As its clinical use becomes more widespread in practice, assessing its safety in real-world settings is essential. Methods: In this research, disproportionality analysis was applied to evaluate the safety of Regadenoson by examining all adverse event (AE) reports since 2004 in the FDA Adverse Event Reporting System (FAERS), in which Regadenoson was identified as the primary suspected drug. The reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma Poisson shrinker (MGPS), and Bayesian confidence propagation neural network (BCPNN) were used to analyze AEs associated with Regadenoson. The Weibull distribution was utilized to model the temporal risk of AEs. Results: The results confirmed some known adverse reactions, such as nausea, shortness of breath (dyspnea), palpitations/vomiting, headache, dizziness, chest pain, and flushing (facial redness or warmth), which were also listed on the drug’s label. New potential adverse reactions not mentioned in the label were identified, including micturition urgency, mental status changes, conversion disorder, eye movement disorder, and genital paraesthesia. This study highlighted the significance of monitoring AEs, particularly right after the start of Regadenoson administration. Conclusions: This study provides preliminary safety data on Regadenoson’s real-world use, corroborating known adverse effects while uncovering new potential risks. These findings offer valuable safety insights for clinicians when prescribing Regadenoson for the use of MPI.

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Abstract Background The blood-brain barrier (BBB) severely limits the delivery of therapeutic agents to the brain. Regadenoson, a Food and Drug Administration-approved adenosine A2 agonist, transiently increases BBB permeability in rodents to a 70 kDa dextran. This multi-institutional, NIH-funded study examined regadenoson’s ability to transiently alter BBB permeability in patients with gliomas. Methods Adults with supratentorial gliomas at low risk for regadenoson complications were treated with 1 of the 7 dose levels known to be safe in humans. Successful BBB disruption was defined as a 10-fold increase in vascular permeability (Ktrans) relative to historic benchmarks. This was assessed by dynamic contrast-enhanced perfusion on magnetic resonance imaging in normal-appearing white matter (NAWM) changes in NAWM and non-enhancing tumors were also quantified using contrast-enhanced T1 subtraction maps. Results Seven patients &amp;lt;45 years old with low-grade gliomas were accrued before the study was prematurely closed. Regadenoson was well tolerated. Following regadenoson, Ktrans in NAWM did not reach the targeted Ktrans threshold (0.04 min−1). Normalized subtraction maps of contrast-enhanced T1-weighted MR signal intensity in NAWM did increase an average of 74% ± 22% (P = .016) after regadenoson. Conclusions No dose of regadenoson significantly elevated Ktrans in NAWM. However, the subtraction maps suggest that regadenoson may lead to a measurable change in gadolinium flux. This coupled with strong preclinical data suggests further investigation is warranted. Noninvasive quantification of BBB permeability in patients is feasible and could evaluate different regadenoson schedules, combination therapies, and other approaches to modify BBB permeability which is critical to improving outcomes in patients with brain tumors. Clinical Trial Registration NCI Protocol #: Adult brain tumor consortium 1804, ClinicalTrials.gov Identifier: NCT03971734, Agent(s): Regadenoson, NSC # 811401, commercially available.

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BACKGROUND: Cardiovascular magnetic resonance with myocardial stress perfusion (stress CMR) is a non-invasive technique that offers an assessment of myocardial function, perfusion, and viability. Regadenoson is a selective cardiac adenosine A2 receptor agonist with fewer side effects than adenosine and a favorable safety profile in older pediatric heart transplant recipients (PHTR). There are limited studies evaluating the hemodynamic response of regadenoson in pediatric patients under general anesthesia (GA). METHODS: We reviewed our experience with regadenoson stress CMR in PHTR under GA from 2020-2024 and compared to a non-GA group of PHTR who underwent regadenoson stress CMR from 2015-2022. Demographic and clinical data were recorded. Hemodynamic response and adverse events were reviewed. CMRs were reviewed for perfusion abnormalities and semi-quantitative analysis was performed using myocardial perfusion reserve index (MPRI). RESULTS: Forty-six PHTR underwent 53 stress CMRs under GA over the study period (mean age 7.8 years; range 3-19 years). All patients received endotracheal intubation and sevoflurane and were monitored during and after regadenoson administration per institutional protocol. Heart rate (HR) prior to regadenoson administration was 84±12 beats/min with a peak of 109±14 beats/min and average mean blood pressure (BP) was 63±12 mmHg with a nadir of 45±8 mmHg. Transient hypotension was observed in 33 (77%) scans, which resolved with phenylephrine. There were no other adverse events. Phenylephrine was used in 48 CMRs (91%) for BP support at the discretion of anesthesia. Thirty-eight PHTR underwent 48 stress CMRs without sedation. CMRs were matched by time since transplant. The non-GA group was significantly older (mean age 15.8 years; p<0.001). GA patients had a larger percent decrease in mean BP compared to non-GA patients (27±17% vs 15±17%; p<0.001) with no difference in HR change. There were no significant differences in rates of qualitative perfusion defects, (11% vs 4%, p=0.18), late gadolinium enhancement or MPRI values between the two groups. CONCLUSION: Regadenoson stress CMR is safe and feasible in PHTR under GA. While hypotension was frequently seen, it improved in all cases with phenylephrine. Semi-quantitative myocardial perfusion analysis by MPRI is feasible in these young patients, however further studies are needed to assess its clinical utility in this population.

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