Effects of Zortress® + Tacrolimus vs. Standard Immunosuppression on Progression of Coronary Artery Calcifications and Bone Disease in de Novo Renal Transplant Recipients

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by University of Kentucky
Sponsor:
Information provided by (Responsible Party):
Hartmut Malluche, MD, University of Kentucky
ClinicalTrials.gov Identifier:
NCT01612299
First received: May 30, 2012
Last updated: August 30, 2013
Last verified: August 2013
  Purpose

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.

Condition Intervention
Renal Transplant
Drug: Zortress® /Everolimus

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effects of Zortress® + Tacrolimus vs. Standard Immunosuppression on Progression of Coronary Artery Calcifications and Bone Disease in de Novo Renal Transplant Recipients

Resource links provided by NLM:


Further study details as provided by University of Kentucky:

Primary Outcome Measures:
  • progression of Coronary Artery Calcification [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    The primary outcome of this study is the proportion of pts in the treatment group who experience a 1yr increase of ≥2.5 for the square-root transformed volume indicating CAC progression. Student's Fisher's Exact T-tests will be used to determine progression of CAC score between control & treatment groups. Secondary objectives 1-3 examine 1yr changes in several measurement outcome variables. Fisher's exact tests & confidence intervals for the difference in proportions will be used to compare the two groups in terms of cardiovascular events, graft rejection, & pt survival.


Estimated Enrollment: 60
Study Start Date: May 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Standard Immunosuppression
Tacrolimus + Myfortic®/Cellcept + Corticosteroids
Drug: Zortress® /Everolimus

Standard immunosuppression: THY 1-1.5 mg/kg/d qd for a total of 6 mg/kg •TAC trough targets 0-3 mo 8-12 ng/ml 4-6 mo 6-10 ng/ml >6 mo 5-8 ng/ml•Myfortic® or CEL 360mg or 500mg po BID, and receiving THY then Myfortic® or CEL 720 mg or 1000mg PO BID once THY induction completed• COR 500mg MET IV pre-op,125mg MET IV q24h x 2 doses (Post-Op Days 1 &2) 20mg Pred PO daily x 2 wks 15mg Pred PO daily x 2 wks 10mg Pred PO daily x 4 wks 5mg Pred PO daily x 4 wks 5 mg Pred PO every other day through mon 12.

Experimental: TAC + Zortress® + COR In this arm patients will stop Myfortic®/CEL and start Zortress® at a dose of 1 mg PO BID with a target level of 3-8 ng/ml.At Zortress® level of at least 3 ng/ml TAC will be dosed to a target range as follows Randomization through mo 3 post-transplant 7-10 ng/ml 4-6 mo post transplant 5-8 ng/ml >6 mo post transplant 4-7 ng/ml.

Other Name: Zortress® /Everolimus
Experimental: Zortress®
Tacrolimus + Zortress® + Corticosteroids
Drug: Zortress® /Everolimus

Standard immunosuppression: THY 1-1.5 mg/kg/d qd for a total of 6 mg/kg •TAC trough targets 0-3 mo 8-12 ng/ml 4-6 mo 6-10 ng/ml >6 mo 5-8 ng/ml•Myfortic® or CEL 360mg or 500mg po BID, and receiving THY then Myfortic® or CEL 720 mg or 1000mg PO BID once THY induction completed• COR 500mg MET IV pre-op,125mg MET IV q24h x 2 doses (Post-Op Days 1 &2) 20mg Pred PO daily x 2 wks 15mg Pred PO daily x 2 wks 10mg Pred PO daily x 4 wks 5mg Pred PO daily x 4 wks 5 mg Pred PO every other day through mon 12.

Experimental: TAC + Zortress® + COR In this arm patients will stop Myfortic®/CEL and start Zortress® at a dose of 1 mg PO BID with a target level of 3-8 ng/ml.At Zortress® level of at least 3 ng/ml TAC will be dosed to a target range as follows Randomization through mo 3 post-transplant 7-10 ng/ml 4-6 mo post transplant 5-8 ng/ml >6 mo post transplant 4-7 ng/ml.

Other Name: Zortress® /Everolimus

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01612299

Contacts
Contact: Hartmut Malluche, MD 8593235049 hhmall@uky.edu
Contact: Roberto Gedaly, MD 8593234661 rgeda2@uky.edu

Locations
United States, Kentucky
University of Kentucky Recruiting
Lexington, Kentucky, United States, 40536
Contact: Hartmut Malluche, MD    859-323-5049    hhmall@uky.edu   
Sponsors and Collaborators
University of Kentucky
Investigators
Principal Investigator: Hartmut Malluche, MD University of Kentucky
Principal Investigator: Roberto Gedaly, MD University of Kentucky
  More Information

No publications provided

Responsible Party: Hartmut Malluche, MD, Professor and Chief, University of Kentucky
ClinicalTrials.gov Identifier: NCT01612299     History of Changes
Other Study ID Numbers: 3048108907
Study First Received: May 30, 2012
Last Updated: August 30, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Bone Diseases
Calcinosis
Coronary Artery Disease
Arteriosclerosis
Musculoskeletal Diseases
Calcium Metabolism Disorders
Metabolic Diseases
Coronary Disease
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Arterial Occlusive Diseases
Vascular Diseases
Everolimus
Sirolimus
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents

ClinicalTrials.gov processed this record on August 21, 2014