A prospective, randomized trial of single-drug versus dual-drug immunosuppression in heart transplantation

The tacrolimus in combination, tacrolimus alone compared (TICTAC) trial

David A. Baran, Mark J. Zucker, Luis H. Arroyo, Margarita Camacho, Marc Goldschmidt, Stephen J. Nicholls, Jeanne Prevost-Fernandez, Candace Carr, Laura Adams, Susan Pardi, Vera Hou, Maria Binetti, Jeanine McCahill, Joanne Chichetti, Valerie Viloria, Mary Gladys SanAgustin, Jennifer Ebuenga-Smith, Leslie Mele, Anthony Martin, Donna Blicharz & 5 others Kathy Wolski, Ludmilla Olesnicky, Fang Qian, Alan L. Gass, Marc Cohen

Research output: Contribution to journalArticle

33 Citations (Scopus)

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. Methods and 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.

Original languageEnglish (US)
Pages (from-to)129-137
Number of pages9
JournalCirculation: Heart Failure
Volume4
Issue number2
DOIs
StatePublished - Mar 1 2011
Externally publishedYes

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Tacrolimus
Heart Transplantation
Immunosuppression
Pharmaceutical Preparations
Allografts
Adrenal Cortex Hormones
Confidence Intervals
Mycophenolic Acid
Biopsy
Survival
Standard of Care
Postoperative Period
Sample Size
Angiography
Heart Failure
Transplants
Therapeutics

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Baran, David A. ; Zucker, Mark J. ; Arroyo, Luis H. ; Camacho, Margarita ; Goldschmidt, Marc ; Nicholls, Stephen J. ; Prevost-Fernandez, Jeanne ; Carr, Candace ; Adams, Laura ; Pardi, Susan ; Hou, Vera ; Binetti, Maria ; McCahill, Jeanine ; Chichetti, Joanne ; Viloria, Valerie ; SanAgustin, Mary Gladys ; Ebuenga-Smith, Jennifer ; Mele, Leslie ; Martin, Anthony ; Blicharz, Donna ; Wolski, Kathy ; Olesnicky, Ludmilla ; Qian, Fang ; Gass, Alan L. ; Cohen, Marc. / A prospective, randomized trial of single-drug versus dual-drug immunosuppression in heart transplantation : The tacrolimus in combination, tacrolimus alone compared (TICTAC) trial. In: Circulation: Heart Failure. 2011 ; Vol. 4, No. 2. pp. 129-137.
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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. Methods and 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.",
author = "Baran, {David A.} and Zucker, {Mark J.} and Arroyo, {Luis H.} and Margarita Camacho and Marc Goldschmidt and Nicholls, {Stephen J.} and Jeanne Prevost-Fernandez and Candace Carr and Laura Adams and Susan Pardi and Vera Hou and Maria Binetti and Jeanine McCahill and Joanne Chichetti and Valerie Viloria and SanAgustin, {Mary Gladys} and Jennifer Ebuenga-Smith and Leslie Mele and Anthony Martin and Donna Blicharz and Kathy Wolski and Ludmilla Olesnicky and Fang Qian and Gass, {Alan L.} and Marc Cohen",
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Baran, DA, Zucker, MJ, Arroyo, LH, Camacho, M, Goldschmidt, M, Nicholls, SJ, Prevost-Fernandez, J, Carr, C, Adams, L, Pardi, S, Hou, V, Binetti, M, McCahill, J, Chichetti, J, Viloria, V, SanAgustin, MG, Ebuenga-Smith, J, Mele, L, Martin, A, Blicharz, D, Wolski, K, Olesnicky, L, Qian, F, Gass, AL & Cohen, M 2011, 'A prospective, randomized trial of single-drug versus dual-drug immunosuppression in heart transplantation: The tacrolimus in combination, tacrolimus alone compared (TICTAC) trial', Circulation: Heart Failure, vol. 4, no. 2, pp. 129-137. https://doi.org/10.1161/CIRCHEARTFAILURE.110.958520

A prospective, randomized trial of single-drug versus dual-drug immunosuppression in heart transplantation : The tacrolimus in combination, tacrolimus alone compared (TICTAC) trial. / Baran, David A.; Zucker, Mark J.; Arroyo, Luis H.; Camacho, Margarita; Goldschmidt, Marc; Nicholls, Stephen J.; Prevost-Fernandez, Jeanne; Carr, Candace; Adams, Laura; Pardi, Susan; Hou, Vera; Binetti, Maria; McCahill, Jeanine; Chichetti, Joanne; Viloria, Valerie; SanAgustin, Mary Gladys; Ebuenga-Smith, Jennifer; Mele, Leslie; Martin, Anthony; Blicharz, Donna; Wolski, Kathy; Olesnicky, Ludmilla; Qian, Fang; Gass, Alan L.; Cohen, Marc.

In: Circulation: Heart Failure, Vol. 4, No. 2, 01.03.2011, p. 129-137.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A prospective, randomized trial of single-drug versus dual-drug immunosuppression in heart transplantation

T2 - The tacrolimus in combination, tacrolimus alone compared (TICTAC) trial

AU - Baran, David A.

AU - Zucker, Mark J.

AU - Arroyo, Luis H.

AU - Camacho, Margarita

AU - Goldschmidt, Marc

AU - Nicholls, Stephen J.

AU - Prevost-Fernandez, Jeanne

AU - Carr, Candace

AU - Adams, Laura

AU - Pardi, Susan

AU - Hou, Vera

AU - Binetti, Maria

AU - McCahill, Jeanine

AU - Chichetti, Joanne

AU - Viloria, Valerie

AU - SanAgustin, Mary Gladys

AU - Ebuenga-Smith, Jennifer

AU - Mele, Leslie

AU - Martin, Anthony

AU - Blicharz, Donna

AU - Wolski, Kathy

AU - Olesnicky, Ludmilla

AU - Qian, Fang

AU - Gass, Alan L.

AU - Cohen, Marc

PY - 2011/3/1

Y1 - 2011/3/1

N2 - 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. Methods and 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.

AB - 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. Methods and 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.

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