title: A prospective, randomized trial of single-drug versus dual-drug immunosuppression in heart transplantation: the tacrolimus in combination, tacrolimus alone compared (TICTAC) trial.
abstract: BACKGROUND
  Cardiac transplantation, a procedure nearly abandoned in the 1970s, has evolved into the standard of care for appropriate patients with end-stage heart failure. Much of this success has been due to improvements in immunosuppression, including the introduction of a triple-drug regimen. Retrospective reports suggested that single-drug immunosuppression with tacrolimus was feasible. As such, a prospective, randomized trial was conducted to test this approach.
  
  
  RESULTS
  One hundred fifty adult de novo heart transplant recipients were enrolled in a prospective, randomized, controlled, open-label trial comparing tacrolimus monotherapy (MONO) with tacrolimus and mycophenolate mofetil therapy (COMBO). Corticosteroids were used in the early postoperative period but discontinued in all patients over 8 to 9 weeks. The primary end point was the composite biopsy score at 6 months after transplant. Patients were followed for 1 to 5 years. The composite biopsy score was similar between groups at 6 and 12 months: 6-month MONO, 0.70 ± 0.44 (95% confidence interval, 0.60 to 0.80) versus COMBO, 0.65 ± 0.40 (95% confidence interval, 0.55 to 0.74; P=0.44). Allograft vasculopathy was assessed by angiography and intravascular ultrasound, with no significant differences noted. Three-year survival was also similar (92.4% MONO versus 97% COMBO; P=0.58, log-rank).
  
  
  CONCLUSIONS
  Addition of mycophenolate to single-agent immunosuppression did not provide an advantage over single-agent immunosuppression in terms of rejection, allograft vasculopathy, or 3-year survival. Corticosteroids, which have traditionally been a mainstay of therapy, were successfully discontinued in all patients. These conclusions are tempered by the limited statistical power associated with a sample size of only 150 patients. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00299221.
authors.affiliation: Newark Beth Israel Medical Center, Newark, NJ 07112, USA. dbaran@sbhcs.com
authors.forename: David A
authors.initials: DA
authors.lastname: Baran
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Zucker
authors.forename: Luis H
authors.initials: LH
authors.lastname: Arroyo
authors.forename: Margarita
authors.initials: M
authors.lastname: Camacho
authors.forename: Marc E
authors.initials: ME
authors.lastname: Goldschmidt
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Nicholls
authors.forename: Jeanne
authors.initials: J
authors.lastname: Prevost-Fernandez
authors.forename: Candace
authors.initials: C
authors.lastname: Carr
authors.forename: Laura
authors.initials: L
authors.lastname: Adams
authors.forename: Susan
authors.initials: S
authors.lastname: Pardi
authors.forename: Vera
authors.initials: V
authors.lastname: Hou
authors.forename: Maria
authors.initials: M
authors.lastname: Binetti
authors.forename: Jeanine
authors.initials: J
authors.lastname: McCahill
authors.forename: Joanne
authors.initials: J
authors.lastname: Chichetti
authors.forename: Valerie
authors.initials: V
authors.lastname: Viloria
authors.forename: Mary Gladys
authors.initials: MG
authors.lastname: Sanagustin
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ebuenga-Smith
authors.forename: Leslie
authors.initials: L
authors.lastname: Mele
authors.forename: Anthony
authors.initials: A
authors.lastname: Martin
authors.forename: Donna
authors.initials: D
authors.lastname: Blicharz
authors.forename: Kathy
authors.initials: K
authors.lastname: Wolski
authors.forename: Ludmilla
authors.initials: L
authors.lastname: Olesnicky
authors.forename: Fang
authors.initials: F
authors.lastname: Qian
authors.forename: Alan L
authors.initials: AL
authors.lastname: Gass
authors.forename: Marc
authors.initials: M
authors.lastname: Cohen
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D001706:Biopsy; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011446:Prospective Studies; D016559:Tacrolimus / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D018084:Ultrasonography, Interventional; D014481:United States
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus