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

• ClinicalTrials.gov Identifier: NCT00299221
• Recruitment Status: Completed
• First Posted: March 6, 2006
• Results First Posted: May 28, 2015
• Last Update Posted: May 28, 2015
• Sponsor: Newark Beth Israel Medical Center
• Collaborator: Astellas Pharma Inc
• Information provided by (Responsible Party): David A. Baran, MD, Newark Beth Israel Medical Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Immunosuppression	Drug: Tacrolimus; Drug: combination therapy	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Tacrolimus In Combination, Tacrolimus Alone Compared (TICTAC Trial): A Prospective Randomized Trial Of Minimized Immunosuppression In Adult Heart Transplant Recipients
• Study Start Date: April 2004
• Actual Primary Completion Date: June 2009
• Actual Study Completion Date: December 2009

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Monotherapy; Tacrolimus alone	Drug: Tacrolimus; tacrolimus; Other Name: Prograf
Active Comparator: Combination therapy; tacrolimus with mycophenolate mofetil	Drug: Tacrolimus; tacrolimus; Other Name: Prograf; Drug: combination therapy; MMF; Other Name: mycophenolate mofetil / CellCept

Outcome Measures

Primary Outcome Measures :

1. Mean International Society for Heart and Lung Transplantation Biopsy Score Over the First 6 Months Post-transplantation [ Time Frame: 6 months ]
   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.

Secondary Outcome Measures :

1. Percent of Patients Alive at One Year Post-transplant [ Time Frame: 1 year ]
   Percent of patients alive at one year post-transplant. In other words, all cause mortality over time
2. Number of Patients With Cytomegalovirus (CMV) at One Year Post-transplant [ Time Frame: 1 year ]
   Number of patients developing cytomegalovirus disease by 1 year post-transplant
3. Number of Patients With Allograft Vasculopathy (CAD) at One Year Post Transplant [ Time Frame: 1 year ]
   Number of patients diagnosed with allograft vasculopathy / coronary artery disease (CAD) at one year post transplant
4. Mean ISHLT Biopsy Score Over First Year Post-transplant [ Time Frame: 1 year ]
   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, New Jersey

Newark Beth Israel Medical Center

Newark, New Jersey, United States, 07112

United States, New York

Mt. Sinai Cardiovascular Institute

New York, New York, United States, 10029

Sponsors and Collaborators

Newark Beth Israel Medical Center

Astellas Pharma Inc

Investigators

• Principal Investigator: David A Baran, MD; Newark Beth Israel Medical Center

More Information

Publications of Results:

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.

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.

• Responsible Party: David A. Baran, MD, Director, Heart Failure and Transplant Research, Newark Beth Israel Medical Center
• ClinicalTrials.gov Identifier: NCT00299221
• Other Study ID Numbers: TICTAC
• First Posted: March 6, 2006
• Results First Posted: May 28, 2015
• Last Update Posted: May 28, 2015
• Last Verified: May 2015

Keywords provided by David A. Baran, MD, Newark Beth Israel Medical Center:

immunosuppression; steroid withdrawal; rejection; coronary disease; cytomegalovirus infection

Additional relevant MeSH terms:

Mycophenolic Acid; Tacrolimus; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Calcineurin Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antibiotics, Antineoplastic; Antineoplastic Agents; Antibiotics, Antitubercular; Antitubercular Agents; Anti-Bacterial Agents; Anti-Infective Agents