Lung transplant recipient survival lags other solid organ recipients, with the main early cause of death being primary graft dysfunction (PGD). PGD occurs in up to 1/3 of all recipients, is driven by the body's innate immune response, and has no known medical therapies for treatment or prevention. Investigators have recently shown that Natural Killer (NK) cells, a key innate immune cell, are critical in causing PGD. Importantly, the investigators found that Maraviroc, an FDA-approved drug that works to inhibit these immune cells, prevented lung injury in mouse models of PGD.
The goal of this clinical trial is to learn if Maraviroc works to treat PGD in Lung Transplant patients who are above the age of 18 and have a PGD risk score greater than 50%. The objectives the study hopes to address are:
To address the safety and tolerability of Maraviroc. To test a strategy for PGD enrichment in a lung transplant population. To measure the efficacy and biological efficacy of using Maraviroc. To study the biochemical, physiologic, and molecular effects of the drug on the body.
This will be a double blind study where patients will either get the Maraviroc drug or a placebo. Researchers will then compare the two groups to address the above objectives.
Participants will:
Take drug Maraviroc or a placebo every 12 hours for 3 days post surgery. Follow up will occur during the entire length of stay at UCSF, about 16 days, with a single 12 month follow up once released.
Male or female ≥18 years of age at the time of lung transplant waitlisting.
Listed for a bilateral lung transplantation.
Written informed consent obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.
PGD risk score > 50% at the time of donor organ offer
Recipient scheduled to receive alternate induction regimen that is cell depleting such as anti-thymocyte globulin or alemtuzumab.
Active chronic pulmonary infection in the recipient that are considered relative contraindications to lung transplantation such as Burkholderia or Mycobacterium abscessus.
Recipients receiving HIV, HCV or HBV positive donor organs. Only documented infections are considered exclusion criteria. Recipients receiving increased risk organs will not be excluded.
Recipient listed for concurrent heart or other solid organ transplantation.
Parallel
Maraviroc
DrugProduct will be administered for 300 mg immediately preceding the lung transplant surgery and then will be administered every 12 hours. There will be 7 total doses. The first 3 will be 300 mg doses and the remaining 4 will be 150 mg doses. Maraviroc will be given oral (PO) or by feeding tube (PFT) in crushed format depending on the route availability.
Placebo
DrugPlacebo in 300 and 150 mg formulations Product will be administered every 12 hours for 3 days. The placebo will be matched in appearance and taste to the Maraviroc and is available in PO and liquid (PFT) formulations.
Incidence of severe Primary Graft Dysfunction
Post-operative outcomes associated with PGD
Will compare the time to extubation from mechanical ventilation (time in minutes)
Other measures of Primary Graft Dysfunction
Maximum PGD grade on post-operative day 0-3.
Biologic markers of efficacy.
Proportion and absolute count of bronchoalveolar lavage NK cells
Mortality within first year
If death occurs within the first year of transplant.
Maraviroc PK evaluations
We will measure maraviroc levels in plasma (ng/mL) at pre-dose and then every 12 hours.
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University of California, San Francisco
Lead sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Collaborator
