A randomized, placebo-controlled trial of aprotinin to reduce primary graft dysfunction following lung transplantation

Purpose: Severe primary graft dysfunction (PGD) is the major early problem following lung transplantation. Aprotinin, a serine protease inhibitor, has many anti-inflammatory properties that might reduce or prevent lung injury. Our hypothesis was that the incidence of PGD could be reduced by a combination of donor lung perfusion and systemic administration of aprotinin to recipients. Methods and Materials: The study was randomized and placebo controlled. Donor lungs were perfused during procurement with 4L Perfadex containing aprotinin (280mg load+70mg/hL) or placebo. Aprotinin or placebo was also administered peri-operatively to the recipients. The study was powered to detect a 10% improvement in the primary endpoint of developing ISHLT grade III PGD anytime within 48hr following the transplant procedure. Results: There were 48 patients randomized. Diagnosis and the use of bypass were different between groups. The study was stopped prematurely at the planned interim analysis point because of published concerns about renal toxicity of aprotinin. There was no difference in the occurrence of the primary endpoint between groups of patients. The median change from the baseline creatinine level at 24, 48, 72hr; 7 and 30d following the transplant was not associated with the administration of aprotinin. Conclusions: There was no statistically significant difference in the incidence of the primary endpoint between groups in the study. Excess renal failure related to aprotinin administration in a patient population at high risk for the event was not observed.