Study to Evaluate Adenosine 2A Receptor Agonist (Regadenoson) in Patients Undergoing Lung Transplantation

Study Overview
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Brief Summary
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This study will evaluate the maximum safe dose and duration of regadenoson (Lexiscan) that can be given to people who are having a lung transplant. Regadenoson will be given as a continuous IV infusion. All participants in the study will receive a regadenoson infusion beginning in the operating room during the lung transplant procedure. Participants will be assigned a certain dose of regadenoson to be given over a 12 or 24 hour period.

Detailed Description
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Lung transplantation currently is one way to treat a variety of serious diseases and conditions such as emphysema, pulmonary fibrosis, and cystic fibrosis. Ischemia Reperfusion Injury (IRI) is a known problem that can happen during the first few days after a lung transplant. IRI can cause swelling of the lungs and low levels of oxygen. The most serious type of IRI can cause the transplanted lung to not work properly, it can even cause death. While new treatments and practices have been put into place to lower the chances of IRI, it is still a difficult problem to overcome after a lung transplant. Medicines called Adenosine 2A receptors (A2AR) have been studied in animals with IRI for many years. Some of these studies suggest that with the use of A2AR medicines, the chance of IRI may be lowered or prevented. Regadenoson is an A2AR drug.

Official Title
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A Phase 1 Open Label Study to Evaluate Adenosine 2A Receptor Agonist (Regadenoson) in Patients Undergoing Lung Transplantation

Conditions
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Lung Transplant

Intervention / Treatment
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* Drug: Regadenoson infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must be undergoing a bilateral lung transplantation for end-stage lung disease and thus meet all criteria to be listed Male or female subject, 18 -75 years of age Subjects must sign a study specific informed consent prior to study entry Subjects must meet all of the following laboratory values: hemoglobin ≥ 6 g/dL, platelets > 75,000/mcL, aspartate aminotransferase (AST/SGOT)/ alanine aminotransferase (ALT /SGPT) < 2.5 X institutional upper limit of normal, serum creatinine < 1.5 mg/dL, INR < 1.5, PTT < 40 seconds Exclusion Criteria: Subject requires preoperative extracorporeal membrane oxygenation (ECMO) Subject has second degree (Mobitz type I or II) or third-degree AV block or sinus node dysfunction Subject has history of a bleeding diathesis Subject has a history of clinically overt stroke within the past 3 years Subject has a history of severe hypertension not adequately controlled with anti-hypertensive medications (Systolic blood pressure ≥ 200 mmHg and/or Diastolic blood pressure ≥ 110 mmHg) Subjects who are receiving chronic anti-coagulation or anti-platelet therapy that would preclude surgery (prophylactic aspirin is acceptable) Subjects with a history of metastatic cancer Subjects with a history of seizure disorder Subjects who are receiving or have received within 30 days any other investigational agents Subjects who have received theophylline or aminophylline within 12 hours of study dosing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: Dose escalation study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regadenoson infusion<br>Dose escalation of Regadenoson infusion | Drug: Regadenoson infusion<br>* Dose escalation of Regadenoson when given as an infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient tolerability of assigned dose and duration | Absence of a dose-limiting toxicity | Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Activation of iNKT cells | Activation of iNKT cells | 24 hours | 
| Clinical Pulmonary Graft Dysfunction (PGD) score | Evaluate for ischemia reperfusion injury | 72 hours | 
| Inflammatory Cytokines in blood and bronchioalveolar lavage | Inflammatory Cytokines in blood and bronchioalveolar lavage | 24 hours |