Regadenoson Infusion of Marginalized Donor Lungs in an EVLP System

NCT04521569 | Completed Early Phase 1 DMC FDA Drug

• 2 other identifiers: UVA-LAU-025R01HL128492-04
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 2

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.

Conditions

Lung Transplant

Keywords

EVLP; Lung Transplantation

Outcome Measures

Primary Outcomes (1)

• Lung Rehabilitation

  The primary endpoint is rehabilitation (yes, no) for marginal donor lungs that undergo ex-vivo perfusion using a "lung box" as assessed by the transplant surgeon and utilizing the "Toronto Method" clinical protocol. Rate of rehabilitation is defined as the proportion of sets of lungs that underwent EVLP with/without Regadenoson treatment and are determined to be eligible for implant.

  30 days

Secondary Outcomes (5)

• Primary Lung Graft Dysfunction (PGD) Score

  72 hours

• Intensive care unit length of stay

  8 weeks

• Using of ECMO

  1 week

• Duration on ventilator post-Operative

  1 month

• 12-month survival

  12 months

Study Arms (2)

EVLP with Regadenoson

EXPERIMENTAL

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.

Drug: Regadenoson

EVLP with Steen solution

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Regadenoson 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).

Also known as: Lexiscan

EVLP with Regadenoson

Placebo 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.

Also known as: Steen solution

EVLP with Steen solution

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At the time of clinical evaluation, the PaO2/FiO2 ≤ 300mm Hg OR
• If the PaO2/FiO2 is \> 300mm hg and the donor has any one of more of the following donor risk factors:
• Multiple blood transfusions
• Pulmonary Edema detected via CXR, Bronchoscopy or palpation of the lungs
• Donation after cardiac death donors
• High risk donor history (example: asphyxia, hanging, drowning)
• 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.
• Stability or improvement of other lung function parameters during EVLP perfusion, such as PVR, compliance, or airway pressures.
• Lungs clinically suitable for transplantation (e.g. without signs of significant contusions, edema, or secretion) in the opinion of the surgical investigator(s).
• 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.
• Male or female subject, 18 -75 years of age.
• Subject agrees to accept EVLP perfused lungs.
• Subjects must sign a study specific informed consent prior to study entry.

You may not qualify if:

• 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.
• Donor has aspirated gastric contents into the lung. Donor lung has significant mechanical lung injury or trauma.
• Donor lung has active infections disease, such as HIV, Hepatitis B or C, HTLV or syphilis.
• Donor lung must not be split and perfused as single lung on EVLP circuit.
• 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.
• \> 10% functional deterioration of other lung parameters during EVLP such as PVR, compliance or airway pressures.
• Subject requires preoperative extracorporeal membrane oxygenation (ECMO).
• Subjects who are receiving or have received within 30 days any other investigational agents.
• Subjects with Burkolderia cepacia.
• Subjects who have had a previous lung transplant.
• 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.
• Pregnant or breastfeeding women.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (2)

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195 |, United States

Location

MeSH Terms

Interventions

regadenoson

Study Officials

• Christine Lau, MD

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: All study team members and subjects will be blinded to treatment assignment with the exception of the statisticians and investigational pharmacist preparing the study treatment.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Surgeon-in-Chief, Department of Surgery

Model Details: Randomization to the EVLP with placebo or EVLP with Regadenoson groups will be performed in a 1:2 ratio.

Study Record Dates

• First Submitted: July 14, 2020
• First Posted: August 20, 2020
• Study Start: June 22, 2020
• Primary Completion: June 23, 2024
• Study Completion: July 31, 2024
• Last Updated: August 5, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)