A randomized, controlled trial of C0- Vs C2-guided therapeutic drug monitoring of cyclosporine in stable heart transplant patients.

Background: Cyclosporine monitoring using 2-hour post-dose samples (C-2) is thought to be more efficacious than using pre-dose levels (C-0) in managing immunosupression for transplant patients. We evaluated the effect of C-2 monitoring on cyclosporine dose and clinical parameters in stable heart transplant patients. Methods: 125 stable heart transplant patients were randomized to C-0 or C-2 monitoring of cyclosporine levels for a period of six months. All patients had both C-0 and C2 samples taken, and clinicians were blinded to one of the samples depending on randomization. The primary endpoint was the relative change in cyclosporine (Neoral) dose during the study period and secondary endpoints were change in creatine clearance, mortality, infection, and acute rejection. Results: There was a significant decrease in the cyclosporine dose for the C-2 group as compared with the C-0 group (-11 mg/day and -26 mg/day respectively, p = 0.0025). No proven rejection episodes Occurred in either group and there was no significant difference in the incidence of infection (C-0 - 6, C-2 - 10; p = 0.14), the change in renal function (change in creatine clearance C-0 +0-54 ml/min; C-2 -0.16 ml/min; p = 0.61), the number of blood tests or dose adjustments between groups over the study, period. Analysis of the blinded samples revealed that the reduction of cyclosporine dose in the C-2 group could not be accounted for by reduced immunosuppression. Conclusion: C-2 monitoring allows a significant cyclosporine dose reduction without compromising patient outcome in stable heart transplant patients. Further studies are required to ascertain whether this dose reduction can be translated into clinical benefit.