A Randomized Trial of CCR5 Inhibition as a Complement to Lung Transplant Induction Immunosuppression
University of California, San Francisco
Summary
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.
Description
This trial seeks to pilot processes to optimize for a multi-center clinical trial of CCR5 inhibition before transplant. Investigators will measure success in enriching a lung transplant population for PGD and will investigate the feasibility of recruitment for a pilot trial of CCR5 inhibition. Investigators will also assess the safety and tolerability of CCR5 inhibition in lung transplant recipients. Investigators will measure key adverse events and assess for drug-drug interactions. In addition, investigators will measure Maraviroc drug levels in plasma and bronchoalveolar lavage to determine…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria: 1. Male or female ≥18 years of age at the time of lung transplant waitlisting. 2. Listed for a bilateral lung transplantation. 3. Written informed consent obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study. 4. PGD risk score \> 50% at the time of donor organ offer 5. Planned induction with basiliximab, mycophenolatge, and prednisone and routine maintenance immunosuppression of tacrolimus, mycophenolate and prednisone. Exclusion Criteria: 1. Recipient scheduled to receive alternate induction regimen…
Interventions
- DrugMaraviroc
Product 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.
- DrugPlacebo
Placebo 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.
Location
- University of California, San FranciscoSan Francisco, California