Regadenoson Infusion of Marginalized Donor Lungs in an EVLP System

NCT ID: NCT04521569

Last Updated: 2024-08-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-22
• Study Completion Date: 2024-07-31

Brief Summary

The purpose of this study is to see if adding a drug called Regadenoson to the EVLP circulation reservoir during perfusion of marginal donor lungs will help increase the likelihood that the donor lungs will become usable for transplantation.

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.

Molecule called Adenosine 2A receptor (A2AR) have been studied in animals with IRI for many years. Some of these studies suggest that with the use of A2AR agonist, the chance of IRI may be lowered or prevented. Regadenoson is a selective A2AR agonist.

Conditions

Lung Transplant

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

EVLP with Regadenoson

Following the routine retrieval procedure of the lungs, they will be placed on the EVLP circuit (XVIVO Perfusion System) and infused with the study drug, Regadenoson.

Group Type: EXPERIMENTAL

Regadenoson

Intervention Type: DRUG

If the donor lungs are randomized the experimental arm, the administration of Regadenoson will be performed at each study site by a qualified medical professional. The donor lungs will be perfused with Regadenoson at a dosage of 1.44 microgram/kg/min (based on donor's weight) for a minimum of three hours and maximum of four hours, using a pediatric syringe pump into the EVLP circuit (XVIVO Perfusion System). The infusion will begin within 10 minutes of the start of the EVLP procedure. Once the EVLP is complete the lungs are re-flushed with Perfadex solution (removing the Steen™ solution and Regadenoson; standard for EVLP).

EVLP with Steen solution

Following the routine retrieval procedure of the lungs, they will be placed on the EVLP circuit (XVIVO Perfusion System) and infused with the same volume of Steen solution.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

If the donor lungs are randomized to the Steen solution arm, the donor lungs will be perfused with placebo at a rate equivalent to the dosage of Regadenoson (1.44 microgram/kg/min), for a minimum of three hours and maximum of four hours, using the same pediatric syringe pump. The infusion will begin within 10 minutes of the start of the EVLP procedure.

Interventions

Regadenoson

If the donor lungs are randomized the experimental arm, the administration of Regadenoson will be performed at each study site by a qualified medical professional. The donor lungs will be perfused with Regadenoson at a dosage of 1.44 microgram/kg/min (based on donor's weight) for a minimum of three hours and maximum of four hours, using a pediatric syringe pump into the EVLP circuit (XVIVO Perfusion System). The infusion will begin within 10 minutes of the start of the EVLP procedure. Once the EVLP is complete the lungs are re-flushed with Perfadex solution (removing the Steen™ solution and Regadenoson; standard for EVLP).

Intervention Type: DRUG

Placebo

If the donor lungs are randomized to the Steen solution arm, the donor lungs will be perfused with placebo at a rate equivalent to the dosage of Regadenoson (1.44 microgram/kg/min), for a minimum of three hours and maximum of four hours, using the same pediatric syringe pump. The infusion will begin within 10 minutes of the start of the EVLP procedure.

Intervention Type: DRUG

Other Intervention Names

Lexiscan; Steen solution

Eligibility Criteria

Inclusion Criteria

1. At the time of clinical evaluation, the PaO2/FiO2 ≤ 300mm Hg OR

2. If the PaO2/FiO2 is > 300mm hg and the donor has any one of more of the following donor risk factors:

1. Multiple blood transfusions

2. Pulmonary Edema detected via CXR, Bronchoscopy or palpation of the lungs

3. Donation after cardiac death donors

4. High risk donor history (example: asphyxia, hanging, drowning)

1. Delta PaO2 greater than 350 mmhg (measured with an FiO2 set at 1.0) at two consecutive time periods at 2, 3, or 4 hours of EVLP.

2. Stability or improvement of other lung function parameters during EVLP perfusion, such as PVR, compliance, or airway pressures.

3. Lungs clinically suitable for transplantation (e.g. without signs of significant contusions, edema, or secretion) in the opinion of the surgical investigator(s).

1. Subjects must be undergoing a single or bilateral lung transplantation for end-stage lung disease and thus meet all criteria to be listed. Single lungs are only allowable when initially placed as bilaterally block on EVLP circuit.

2. Male or female subject, 18 -75 years of age.

3. Subject agrees to accept EVLP perfused lungs.

4. Subjects must sign a study specific informed consent prior to study entry.

Exclusion Criteria

1. Donor lung has significant pneumonia as defined by positive bacterial growth in blood culture (not related to other source of infection) or persistent purulent, un-clearable secretions on bronchoscopy OR as determined by the investigator.

2. Donor has aspirated gastric contents into the lung. Donor lung has significant mechanical lung injury or trauma.

3. Donor lung has active infections disease, such as HIV, Hepatitis B or C, HTLV or syphilis.

4. Donor lung must not be split and perfused as single lung on EVLP circuit.

1. Delta PaO2 less than 350 mmHg (measured with FiO2 set at 1.0) at two consecutive time periods at 2, 3 or 4 hours of ex Vivo perfusion.

2. > 10% functional deterioration of other lung parameters during EVLP such as PVR, compliance or airway pressures.

1. Subject requires preoperative extracorporeal membrane oxygenation (ECMO).

2. Subjects who are receiving or have received within 30 days any other investigational agents.

3. Subjects with Burkolderia cepacia.

4. Subjects who have had a previous lung transplant.

5. Subjects who have an uncontrolled concurrent illness including, but not limited to an ongoing or active infection, uncontrolled congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements per investigator discretion.

6. Pregnant or breastfeeding women.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

Christine Lau

Surgeon-in-Chief, Department of Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christine Lau, MD

Role: PRINCIPAL_INVESTIGATOR

University of Maryland, Baltimore

Locations

University of Maryland Medical Center

Baltimore, Maryland, United States

Cleveland Clinic

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

5R01HL128492-04

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UVA-LAU-02

Identifier Type: -

Identifier Source: org_study_id