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 (C2) is thought to be more efficacious than using pre-dose levels (C0) in managing immunosuppression for transplant patients. We evaluated the effect of C2 monitoring on cyclosporine dose and clinical parameters in stable heart transplant patients.


METHODS
125 stable heart transplant patients were randomized to C0 or C2 monitoring of cyclosporine levels for a period of six months. All patients had both C0 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 C2 group as compared with the C0 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 (C0 6, C2 10; p = 0.14), the change in renal function (change in creatine clearance C(0) +0.54 ml/min; C2 -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 C2 group could not be accounted for by reduced immunosuppression .


CONCLUSIONS
C2 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.
Mathias
Helen C
HC
Scottish Cardiopulmonary Transplant Unit, Glasgow Royal Infirmary, Glasgow, UK. hmathias@doctors.org.uk
Ozalp
Farük
F
Will
Malcolm B
MB
Borland
William
W
Payne
Carol
C
Kerr
Myra
M
Lockhart
Jane
J
Murday
Andrew J
AJ
D000368:Aged; D019540:Area Under Curve; D003404:Creatinine / Q000378:metabolism; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007239:Infections; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D011183:Postoperative Complications; D011446:Prospective Studies; D016019:Survival Analysis
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine