Thorac Cardiovasc Surg 2005; 53 - V3
DOI: 10.1055/s-2005-861890

A multicenter trial to investigate the efficacy and safety of everolimus versus Azathioprine in stable Lung Transplant Recipients (LTR) –24 months results

T Pühler 1, S Hirt 1, J Cremer 1, V Valentine 2, M Krauss 3, A Haverich 4
  • 1Universitätsklinikum SH Campus Kiel, Klinik für Herz- und Gefäßchirurgie, Kiel
  • 2Clinic Foundation New Orleans, New Orleans
  • 3Novartis Pharma GmbH, Nürnberg
  • 4Medizinische Hochschule Hannover, Thorax-, Herz- und Gefäßchirurgie, Hannover

Everolimus (RAD, Certican®), a proliferation signal inhibitor, may inhibit the decline in lung function and improve survival in LTRs.

Material and Methods: A 3-year randomized, double-blind trial of stable LTRs without Bronchiolitis Obliterans Syndrome (BOS) was prospectively performed to compare the efficacy and safety of everolimus (3mg/day) vs. azathioprine (AZA, 1–3mg/kg/day) in combination with cyclosporine A and steroids. The primary composite efficacy endpoint was decline of FEV1>15% from study entry (ΔFEV1>15%), graft loss, death or loss to follow-up. Other efficacy endpoints included (ΔFEV1>15%), incidence of BOS, obliterative bronchiolitis and incidence of acute rejection (AR).

Results: 213 Patients were randomized, 101 patients received everolimus and 112 AZA. At 12 months, everolimus demonstrated superiority over AZA for the composite efficacy endpoint, (ΔFEV1>15%), and AR. At 24 months, everolimus was comparable to AZA with regard to the composite efficacy endpoint 43.6% vs. 44.6% (p=0.874). Everolimus patients showed a lower rate of biopsy proven AR 11.9% vs. 25.9% (p<0.001). There was a trend favoring everolimus at other efficacy endpoints: ΔFEV1>15% (34.7% vs. 41.1%), obliterative broncholitis (22.8% vs. 30.4%). Overall incidence of adverse events (AE) was similar between everolimus and AZA. Malignancy rates were low and similar in both groups. Severe AE (67% vs. 39%) and non-fatal serious AE (59% vs. 41%) were higher for everolimus, as well as bacterial and fungal infections. Overall safety profile of everolimus was similar to that seen in heart and kidney studies with elevated creatinine, cholesterol and triglyceride values.

Conclusions: At 24 months everolimus showed comparable results to AZA with regard to the composite primary efficacy endpoint and statistically significant lower rates of biopsy proven AR.