Clinical trial NCT04521569: Regadenoson Infusion of Marginalized Donor Lungs in an EVLP System
Official title: A Randomized, Blinded, Multi-site, Pilot Study to Evaluate Adenosine 2A Receptor Agonist (REGADENOSON) in the Rehabilitation of Marginal Donor Lungs.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Lung Transplant
Keywords: EVLP
Lung Transplantation
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2020-08-20
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomization to the EVLP with placebo or EVLP with Regadenoson groups will be performed in a 1:2 ratio.
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion Criteria:

Donor Lung Inclusion Criteria for EVLP

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)

Donor lung Inclusion Criteria for Transplant Suitability after EVLP

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).

Participant Inclusion Criteria

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:

Donor Lung Exclusion Criteria for EVLP

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.

Donor Lung Exclusion Criteria for Transplant Suitability after EVLP (All of the below must be negative)

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.

Participant Exclusion Criteria

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.

Primary outcomes:
measure: Lung Rehabilitation
timeFrame: 30 days
Secondary outcomes:
measure: Primary Lung Graft Dysfunction (PGD) Score
timeFrame: 72 hours
measure: Intensive care unit length of stay
timeFrame: 8 weeks
measure: Using of ECMO
timeFrame: 1 week
measure: Duration on ventilator post-Operative
timeFrame: 1 month
measure: 12-month survival
timeFrame: 12 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
affiliation: University of Maryland, Baltimore
name: Christine Lau, MD
role: PRINCIPAL_INVESTIGATOR
References: