Roche Laboratories, following discussion with the FDA ( Food and Drug Administration ), informed Health Care Professionals of important safety information regarding the termination of the Heart Spare The Nephron ( STN ) clinical trial due to an observed increased incidence of grade IIIA acute rejection in heart transplant patients switched from a calcineurin inhibitor ( CNI ) in combination with CellCept ( Mycophenolate Mofetil) to Rapamune ( Sirolimus ) in combination with CellCept at 12 weeks post heart transplantation.
The safety and efficacy of CellCept in combination with Sirolimus following withdrawal of initial calcineurin inhibitor therapy has not been established.
The Heart STN clinical trial was designed to investigate whether renal function benefit could be achieved with the withdrawal of calcineurin inhibitor therapy followed by the introduction of Sirolimus at 12 weeks post heart transplantation.
Following heart transplantation, all patients received the immunosuppressive therapy for their center, including CellCept in combination with either Cyclosporine ( Neoral ) or Tacrolimus ( Prograf ), and corticosteroids.
Fifteen patients had been randomized to one of two arms when the study was stopped prematurely. In the treatment group, seven heart transplant recipients were switched from CNI to Sirolimus at 12 weeks post heart transplantation while maintaining CellCept ( CellCept dosing to achieve a protocol suggested minimum MPA trough of 2.0 microg/mL ) and corticosteroid therapy.
In the control treatment arm, eight patients continued to receive CNI, CellCept and corticosteroid therapy.
Of the seven patients randomized to the Sirolimus, CellCept and corticosteroid arm, four experienced a grade IIIA rejection within 5 weeks of discontinuing the CNI.
Three of the four rejection episodes occurred at one center in the United States. Three of these patients responded well to treatment with corticosteroids and the fourth patient recovered after experiencing hemodynamic compromise.
No cases of graft loss occurred. There were no similar episodes of rejection in patients receiving the calcineurin based regimen ( CNI, CellCept and corticosteroids ).
F. Hoffmann-La Roche Ltd. terminated this clinical trial when these results were reported. There is limited data available from this study to draw a firm conclusion regarding the difference in the rejection rate between the two treatment arms.
CellCept is indicated for the prophylaxis of organ rejection in patients receiving allogeneic renal, cardiac or hepatic transplants. CellCept should be used concomitantly with Cyclosporine and corticosteroids.
Source: FDA, 2007