Clinical trial NCT01612299: Effects of Zortress® + Tacrolimus vs. Standard Immunosuppression on Progression of Coronary Artery Calcifications and Bone Disease in de Novo Renal Transplant Recipients
Official title: Effects of Zortress® + Tacrolimus vs. Standard Immunosuppression on Progression of Coronary Artery Calcifications and Bone Disease in de Novo Renal Transplant Recipients
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Renal Transplant
Lead sponsor: University of Kentucky
Sponsor class: OTHER
First posted: 2012-06-05
Enrollment: 0
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary objectives: A. To evaluate the effect of Zortress® versus standard immunosuppression therapy on progression of CAC as evidenced by changes in Agatston scores from baseline and at 6, and 12 months in renal transplantation patients. B. To investigate progression of CAC in patients undergoing renal transplantation within the study period.

Secondary objectives:

1. To evaluate in renal transplantation the effect of Zortress® versus standard immunosuppression therapy on bone mass as evidenced by changes in quantitative computed tomography (QCT) and dual energy X-ray absorptiometry (DXA).
2. To evaluate in renal transplantation the effect of Zortress® versus standard immunosuppression therapy on activity of bone forming and resorbing cells as evidenced by changes in bone histology.
3. To evaluate in renal transplantation the effect of Zortress® versus standard immunosuppression therapy on biochemical parameters of bone turnover as evidenced by changes in serum Parathyroid Hormone (PTH), Bone-Specific Alkaline Phosphatase (BSAP), Tartrate-Resistant Acid Phosphatase (TRAP), Sclerostin, Receptor Activator of Nuclear factor Kappa B Ligand (RANKL), Osteoprotegerin (OPG), , serum CTX (C-terminal telopeptide of type 1 collagen), and urinary NTX (N-terminal cross link telopeptide).
4. To evaluate in renal transplantation the effect of Zortress® versus standard immunosuppression therapy on cardiovascular events, graft rejection and patient survival.


Eligibility criteria: Inclusion Criteria:

* De novo renal transplant recipients (from deceased or living donors) between 18-70 years of age
* Willingness to participate in the study and comply with study requirements as evidenced by signed IRB-approved informed consent

Enrollment Exclusion Criteria:

* Previous solid organ transplant
* Known hypersensitivity to any of the study drugs, or their class, or to any of their excipients
* Recipients of an investigational drug within 30 days before transplant
* Any abnormal physical or laboratory findings of clinical significance which would interfere with conduct of the study
* Females of childbearing potential who are planning to become pregnant, who are pregnant and/or lactating, or unwilling to use medically approved means of contraception

Randomization Exclusion Criteria:

* Platelet count \<75,000/mm
* White blood cell count of \< 2,000/mm³
* Hypercholesterolemia (\>400 mg/dL) or hypertriglyceridemia (\>500 mg/dL) despite lipid-lowering therapy
* Presence of any clinically significant infection requiring IV antibiotics
* Positive serum HCG (women of childbearing potential)
* Spot urine protein to creatinine ratio (UPr/Cr ) ≥ 0.5
* Any biopsy-confirmed acute rejection since transplant
* Baseline CAC score \< 100 at baseline reading

Primary outcomes:
measure: progression of Coronary Artery Calcification
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
Study officials:
affiliation: University of Kentucky
name: Hartmut Malluche, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Kentucky
name: Roberto Gedaly, MD
role: PRINCIPAL_INVESTIGATOR
References: