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

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

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.

Study Overview

• Status: Unknown
• Conditions: Lung Transplant
• Intervention / Treatment: Drug: Regadenoson infusion

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • University of Maryland
      • Contact: Amanda Bartosic, MBA; Phone Number: 410-328-1641; Email: ABartosic@som.umaryland.edu
      • Principal Investigator: Christine Lau, MD
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Active, not recruiting
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

  1. hemoglobin ≥ 6 g/dL,
  2. platelets > 75,000/mcL,
  3. aspartate aminotransferase (AST/SGOT)/ alanine aminotransferase (ALT /SGPT) < 2.5 X institutional upper limit of normal,
  4. serum creatinine < 1.5 mg/dL,
  5. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Regadenoson infusion; Dose escalation of Regadenoson infusion	Drug: Regadenoson infusion; Dose escalation of Regadenoson when given as an infusion

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Christine Lau, MD
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Christine Lau, MD, University of Maryland, Baltimore

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2017
• Primary Completion (Anticipated): August 1, 2021
• Study Completion (Anticipated): August 1, 2022

Study Registration Dates

• First Submitted: March 1, 2017
• First Submitted That Met QC Criteria: March 6, 2017
• First Posted (Actual): March 7, 2017

Study Record Updates

• Last Update Posted (Actual): June 4, 2020
• Last Update Submitted That Met QC Criteria: June 3, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Purinergic Agents; Purinergic P1 Receptor Agonists; Purinergic Agonists; Adenosine A2 Receptor Agonists; Regadenoson
• Other Study ID Numbers: UVA-LAU-01; 1R01HL128492-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No