Safety Outcomes of Lower Immunosuppression Versus Traditional Immunosuppression in Heart Transplant Recipients (TICTAC)

Tacrolimus In Combination, Tacrolimus Alone Compared (TICTAC Trial): A Prospective Randomized Trial Of Minimized Immunosuppression In Adult Heart Transplant Recipients

This was a study to compare less intense immunosuppression with a more traditional approach. The hypothesis was that less immunosuppression will provide similar protection against rejection than typical 2-3 drug therapy.

Study Overview

• Status: Completed
• Conditions: Immunosuppression
• Intervention / Treatment: Drug: Tacrolimus; Drug: combination therapy

Detailed Description

This was a prospective, randomized, controlled (open-label) trial of 2 different strategies of immunosuppression in de novo post-heart transplant patients. The hypothesis was that immunosuppression with tacrolimus and mycophenolate mofetil, coupled with rapid steroid weaning would provide similar anti-rejection efficacy as tacrolimus with only a 2 week course of mycophenolate mofetil but including the same rapid steroid wean.

The primary endpoint was the mean International Society for Heart and Lung Transplantation (ISHLT) biopsy score over the first 6 months post-transplant. Secondary endpoints included the incidence of adverse events over the first year post-transplant, as well as all-cause mortality, 12 month ISHLT biopsy score (mean), along with the incidence of proven cytomegalovirus disease. In addition, the incidence of allograft vasculopathy as assessed by angiography or intravascular ultrasound was compared between groups.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Medical Center
  • New York
    • New York, New York, United States, 10029
      • Mt. Sinai Cardiovascular Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult (at least 18 years old)
• Undergoing a first heart transplant (no heart/kidney transplants), who receive their transplant at one of the study sites
• Specifically INCLUDED are patients on ventricular assist devices, and allosensitized recipients

Exclusion Criteria:

• Age less than 18
• Inability to provide proper informed consent
• Combined organ transplantation
• Re-Transplantation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Monotherapy; Tacrolimus alone	Drug: Tacrolimus; tacrolimus; Other Names: Prograf
Active Comparator: Combination therapy; tacrolimus with mycophenolate mofetil	Drug: Tacrolimus; tacrolimus; Other Names: Prograf; Drug: combination therapy; MMF; Other Names: mycophenolate mofetil / CellCept

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean International Society for Heart and Lung Transplantation Biopsy Score Over the First 6 Months Post-transplantation	Mean ISHLT biopsy score Biopsies of the heart may be various grades and each is assigned a numerical score. Grade 0 is 0 points, 1A = 1, 1B = 2, grade 2 = 3, grade 3A = 4, Grade 3B = 5, and grade 4 = 6 units. The mean biopsy score is the numeric average of the biopsy scores for the first 6 post-transplant months. Best value is 0, worst score is 6.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Patients Alive at One Year Post-transplant	Percent of patients alive at one year post-transplant. In other words, all cause mortality over time	1 year
Number of Patients With Cytomegalovirus (CMV) at One Year Post-transplant	Number of patients developing cytomegalovirus disease by 1 year post-transplant	1 year
Number of Patients With Allograft Vasculopathy (CAD) at One Year Post Transplant	Number of patients diagnosed with allograft vasculopathy / coronary artery disease (CAD) at one year post transplant	1 year
Mean ISHLT Biopsy Score Over First Year Post-transplant	Mean ISHLT biopsy score Biopsies of the heart may be various grades and each is assigned a numerical score. Grade 0 is 0 points, 1A = 1, 1B = 2, grade 2 = 3, grade 3A = 4, Grade 3B = 5, and grade 4 = 6 units. The mean biopsy score is the numeric average of the biopsy scores for the first 6 post-transplant months. Best value is 0, worst score is 6.	1 year

Collaborators and Investigators

• Sponsor: Newark Beth Israel Medical Center
• Collaborators: Astellas Pharma Inc
• Investigators: Principal Investigator: David A Baran, MD, Newark Beth Israel Medical Center

Publications and helpful links

General Publications

• Baran DA, Zucker MJ, Arroyo LH, Alwarshetty MM, Ramirez MR, Prendergast TW, Goldstein DJ, Camacho M, Gass AL, Carr C, Cohen M. Randomized trial of tacrolimus monotherapy: tacrolimus in combination, tacrolimus alone compared (the TICTAC trial). J Heart Lung Transplant. 2007 Oct;26(10):992-7. doi: 10.1016/j.healun.2007.07.022.
• Baran DA, Zucker MJ, Arroyo LH, Camacho M, Goldschmidt ME, 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. A prospective, randomized trial of single-drug versus dual-drug immunosuppression in heart transplantation: the tacrolimus in combination, tacrolimus alone compared (TICTAC) trial. Circ Heart Fail. 2011 Mar;4(2):129-37. doi: 10.1161/CIRCHEARTFAILURE.110.958520. Epub 2011 Jan 7.

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: March 2, 2006
• First Submitted That Met QC Criteria: March 2, 2006
• First Posted (Estimate): March 6, 2006

Study Record Updates

• Last Update Posted (Estimate): May 28, 2015
• Last Update Submitted That Met QC Criteria: May 26, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: immunosuppression; coronary disease; rejection; cytomegalovirus infection; steroid withdrawal
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Tacrolimus; Mycophenolic Acid
• Other Study ID Numbers: TICTAC