Randomized Trial of 2 Antibody Induction Steroid Avoidance Protocols

NCT01172418 | Completed Phase 4 Results DMC

• 1 other identifier: IRB #20057672
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the present study is to determine which antibody induction regimen will result in a safer and more effective method to use with steroid avoidance in renal transplant recipients. Patients receiving either first cadaveric or non-HLA identical living donor kidney transplants will be preoperatively randomized into 2 groups.

Conditions

Transplant; Failure, Kidney

Keywords

adult; primary kidney transplant recipient

Outcome Measures

Primary Outcomes (1)

• Incidence of Acute Rejection at One Year Post-transplant

  at one year post-transplant

Secondary Outcomes (4)

• Graft Survival

  at 1 year post-transplant

• Graft Survival

  at 3 years post-transplant

• Patient Survival

  at 1 year post-transplant

• Patient Survival

  at 3 years post-transplant

Study Arms (2)

Thymoglobulin and Daclizumab

ACTIVE COMPARATOR

Group I: Our standard steroid avoidance protocol, i.e., 3 daily doses of 1 mg/kg of Thymoglobulin®, the first to be infused at surgery, accompanied by 2 doses of anti-CD25 humanized monoclonal antibody, the first also to be given at surgery, and the second 2 weeks later. (controls)

Drug: Daclizumab; Drug: Thymoglobulin

Thymoglobulin and Alemtuzumab

EXPERIMENTAL

Group II: A new steroid avoidance protocol in which 1 dose of 1 mg/kg of Thymoglobulin® is to be infused at surgery followed by 1 dose of alemtuzumab (Campath-1H) at 0.3 mg/kg within 24 hours. No further antibody therapy will be used.

Drug: Alemtuzumab; Drug: Thymoglobulin

Interventions

Alemtuzumab DRUG

Alemtuzumab used as part of combined Induction.

Also known as: Campath-1H (Alemtuzumab)

Thymoglobulin and Alemtuzumab

Daclizumab DRUG

Daclizumab used as part of combined induction.

Also known as: Zenapax (Daclizumab)

Thymoglobulin and Daclizumab

Thymoglobulin DRUG

Thymoglobulin used as part of combined induction.

Also known as: rATG (rabbit antithymocyte globulin)

Thymoglobulin and Alemtuzumab; Thymoglobulin and Daclizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has been fully informed and has signed a dated IRB approval informed consent form and is willing to follow study procedures for the extent of the study (12 months). Parent or legal guardian must provide written consent for patients \<18 years of age.
• Age 18-70 years
• Weight \> 40 kg
• Primary renal allograft: living or deceased donor
• Negative standard crossmatch for T cells. All deceased donor-recipient pairs matched for a minimum of 1 HLA DR antigen. (Standard at our center.)
• Women of childbearing potential will be required to have a negative qualitative serum pregnancy test and agree to use an adequate method of contraception for the study duration.
• Males and females are to be studied equivalently as they become available for transplantation using these criteria.

You may not qualify if:

• \. Patient has previously received or is receiving an organ transplant other than a kidney.
• \. Patient is receiving an ABO incompatible donor kidney. 3. Recipient or donor is seropositive for human immunodeficiency (HIV), Hepatitis C viruses, or Hepatitis B virus antigenemia.
• \. Patient has a current malignancy or a history of malignancy (within the past 5 years), except non-metastatic basal or squamous cell carcinoma of the skin that has been treated successfully, or carcinoma in situ of the cervix that has been treated successfully.
• \. Patients with significant liver disease, defined as having during the past 28 days continuously elevated AST (SGOT) and/or ALT (SGPT) levels greater than 3 times the upper value of the normal range of this center.
• \. Patient has uncontrolled concomitant infections and/or severe diarrhea, vomiting, active upper gastro-intestinal tract malabsorption or an active peptic ulcer or any other unstable medical condition that could interfere with study objectives.
• \. Patient is currently participating in another clinical trial of an investigational drug in the 30 days prior to transplant.
• \. Patient will be receiving any immunosuppressive agent other than those prescribed in the study.
• \. Patient is unable to take medications orally or via nasogastric tube by the morning of the second day following completion of the transplant procedure (i.e., skin closure).
• \. Patient is receiving or may require warfarin, fluvastatin, or herbal supplements during the study.
• \. Concurrent use of astemizole, pimozide, cisapride, terfenadine, or ketoconazole.
• \. Patient has a known hypersensitivity to tacrolimus, Thymoglobulin®, IL-2 receptor inhibitor monoclonal antibodies, alemtuzumab, sirolimus, MMF, Myfortic®, or corticosteroids.
• \. Patient is pregnant or lactating. 14. Patients with a screening/baseline (or within 96 hours of transplant) total white blood cell count \<4000/mm3; platelet count \<100,000/mm3; fasting triglycerides \>400 mg/dl (\>4.6 mmol/L); fasting total cholesterol \>300 mg/dl (\>7.8 mmol/L); fasting HDL-cholesterol \<30 mg/dl; fasting LDL-cholesterol \>200 mg/dl.
• \. Patient is unlikely to comply with the visits scheduled in the protocol. 16. Patient has any form of substance abuse, psychiatric disorder or a condition that, in the opinion of the investigator, may invalidate communication with the investigator.
• \. If tacrolimus cannot be instituted for longer than 5 days postoperatively.

Sponsors & Collaborators

• University of Miami: lead

Study Sites (1)

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Related Publications (1)

• Ciancio G, Gaynor JJ, Sageshima J, Guerra G, Zarak A, Roth D, Brown R, Kupin W, Chen L, Hanson L, Tueros L, Ruiz P, Livingstone AS, Burke GW 3rd. Randomized trial of dual antibody induction therapy with steroid avoidance in renal transplantation. Transplantation. 2011 Dec 27;92(12):1348-57. doi: 10.1097/TP.0b013e3182384b21.

  PMID: 22027927 RESULT

MeSH Terms

Interventions

Alemtuzumab; Daclizumab; thymoglobulin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: George W. Burke, M.D.
• Organization: University of Miami

gburke@med.miami.edu

305-355-5315

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Kidney and Kidney-Pancreas Transplantation

Study Record Dates

• First Submitted: June 10, 2010
• First Posted: July 29, 2010
• Study Start: February 1, 2006
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: September 28, 2023
• Results First Posted: August 20, 2014

Record last verified: 2023-09

Locations

US (1)