Abstract 2458: Tacrolimus In Combination, Tacrolimus Alone Compared (TICTAC Trial): A Prospective Randomized Trial Of Minimized Immunosuppression In Adult Heart Transplant Recipients
Background: Previous retrospective studies have shown that tacrolimus monotherapy (TAC) is feasible in heart transplant patients (txp pts). We conducted a prospective, randomized, open-label, two-center trial comparing TAC / mycophenolate mofetil (MMF) therapy to TAC monotherapy. It was hypothesized that allograft rejection would be similar between groups.
Methods: From 4/04–3/07, 100 de novo adult txp patients were enrolled. Induction therapy was not utilized. All pts received TAC / MMF / steroids and randomized to either discontinue MMF at 2 weeks post-txp ( MONO ), or remain on TAC/MMF ( COMBO ). Steroids were weaned in all pts, with a target of 16 weeks in the first 25 pts and over 8–9 weeks thereafter. Target TAC levels were 9–11 ng/dl in both groups. The primary endpoint was mean 6 month ISHLT biopsy score. Intravascular ultrasound (IVUS) was conducted at baseline and yearly.
Results: 52 pts were randomized to MONO and 48 to COMBO. Demographics are described in the table⇓ below. Age, gender, and race were similar between groups. The time to steroid discontinuation was not significantly different between groups (median 88 ± 10.5 days COMBO vs. 90.5 ± 9.9 days, p=0.68). The primary endpoint, mean 6-month biopsy score was not significantly different between groups (0.65 ± 0.04, MONO vs. 0.65 ± 0.04, COMBO, p=0.79). With one year follow-up, the freedom from ISHLT grade 2R/3R rejection was similar between groups (rejection-free 89 %, COMBO, 85 % MONO, p=0.45). Cytomegalovirus infection was seen in 4 patients (2 in each group). 2 year survival was similar (96 % MONO, 94 % COMBO, p=0.82). The average change in intimal thickness by IVUS was similar between groups (0.37 ± 0.08 mm, COMBO vs 0.39 ± 0.08 mm, MONO).
Conclusion: TAC monotherapy was well tolerated, and associated with equivalent rejection, infection, survival and changes in intimal thickening as compared to TAC/MMF therapy. Rapid steroid weaning was tolerated in all patients. Further study of this approach is warranted.