Safety Outcomes of Lower Immunosuppression Versus Traditional Immunosuppression in Heart Transplant Recipients

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Immunosuppression

Intervention / Treatment
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* Drug: Tacrolimus
* Drug: combination therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Monotherapy<br>Tacrolimus alone | Drug: Tacrolimus<br>* tacrolimus<br>* Other names: Prograf;|
| Active Comparator: Combination therapy<br>tacrolimus with mycophenolate mofetil | Drug: Tacrolimus<br>* tacrolimus<br>* Other names: Prograf;Drug: combination therapy<br>* MMF<br>* Other names: mycophenolate mofetil / CellCept;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immunosuppression, steroid withdrawal, rejection, coronary disease, cytomegalovirus infection