A PRELIMINARY-REPORT OF DILTIAZEM AND KETOCONAZOLE - THEIR CYCLOSPORINE-SPARING EFFECT AND IMPACT ON TRANSPLANT OUTCOME

A prospective randomized trial was conducted to compare the effect of diltiazem (DILT) with ketoconazole (KETO) on sparing of cyclosporine d ose and renal transplant outcome. Renal allograft recipients 18 years old and older were eligible for the study. Triple immunosuppression (T RIPLE) including prednisone, azathioprine, and CsA was administered to all patients. The maintenance CsA dose varied by study group. Patient s were randomized to receive one of three treatment strategies: group 1-TRIPLE (CsA 8 mg(kg/day); group 2-TRIPLE (CsA 6 mg/kg(day) + DILT (6 0 mg b.i.d.); group 3-TRIPLE (CsA 3 mg/kg/day) + KETO (200 mg/day). Mo dification of the DILT dose was allowed as needed to effect blood pres sure control in group 2 patients. Mean 1-month CsA dose reductions wer e 30% and 60% of controls in group 2 and 3, respectively. A continued effect over time was observed in patients administered KETO but not DI LT. At 1 year patients taking KETO required an average of 77% less CsA than the average dose necessary to effect similar parent CsA blood le vels when no enzyme inhibitor was used. The use of KETO and DILT for 1 year allowed for 53% and 14% reductions in CsA cost, respectively. Th ese savings include the cost of the KETO or DILT. Serum creatinines, m ean arterial pressure (MAP), and incidence of liver function abnormali ties were similar throughout treatment groups. The rate of rejection, time to rejection onset, and survival (GS/PS) were not different among the groups. Fungal infections were fewer in patients treated with KET O (12%) than in controls (16%) and patients randomized to DILT (19%). KETO failed to prevent Aspergillus infection in one individual. The in vestigation failed to identify any harmful result of treating renal al lograft recipients with either DILT or KETO for the purpose of reducin g CsA expense.