Phase 2 N=12 Treatment

Sirolimus and Thymoglobulin to Prevent Kidney Transplant Rejection

Kidney Failure

Bottom Line

View on ClinicalTrials.gov: NCT00006178 ↗

Enrolled (actual)

Serious AEs

25.0%

Results posted

Feb 2010

Primary outcome: Primary: Serum Creatinine Concentration — 112 umol/L

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Sirolimus (Drug); Thymoglobulin (Drug)
Age: Pediatric, Adult, Older Adult
Sex: All
Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Primary completion: Dec 2007

Outcome Measures

Outcome	Result	p-value
PRIMARY Serum Creatinine Concentration	107	—
PRIMARY Serum Creatinine Concentration	107	—
SECONDARY Glomerular Filtration Rate (Flow Rate of Filtered Fluid Through the Kidney)	74.2	—
SECONDARY Glomerular Filtration Rate (Flow Rate of Filtered Fluid Through the Kidney)	74.2	—

Summary

This study will test the safety and effectiveness of two drugs, Sirolimus and Thymoglobulin, for preventing rejection of transplanted kidneys. Standard anti-rejection therapy uses a combination of drugs, such as cyclosporine, tacrolimus, azathioprine, steroids, and others, that are taken daily for life. However, even with this daily therapy, more than half of kidney recipients slowly reject their transplant within 10 years. Both Thymoglobulin, an antibody, and Sirolimus, an anti-rejection drug, prevent rejection by lowering the response of the immune system to the transplanted organ. Thymoglobulin is given in the pre- and postoperative period, and Sirolimus is taken long term. Patients who receive a kidney transplant at the National Institutes of Health Clinical Center are eligible for this study. Candidates will be screened with a medical history, physical examination, and blood and urine tests. Participants will undergo a kidney transplant. Before the surgery, a central line (intravenous catheter), through which blood and medicine can be given, is placed in the neck or chest. Patients may also undergo leukapheresis, a procedure for collecting white blood cells. The cells can be stored for transfusion later if white cell counts drop following Thymoglobulin treatment. For this procedure, blood is drawn from a needle placed in the arm and flows into a machine that separates the blood components by spinning. The white cells are collected in a bag and the red cells and plasma are returned through a second needle in the other arm. Thymoglobulin will be given intravenously the day before the transplant and days 1 through 9 after the operation. Sirolimus will be taken by mouth, mixed with water or orange juice. Sirolimus therapy starts the day of the transplant and continues for life. Follow-up study visits will be scheduled weekly for the first month after the transplant, then every 6 months for 1 year and then once a year for 4 years. Procedures during these visits may include blood and urine tests, physical examination, and check of vital signs (i.e., blood pressure, heart rate, breathing rate, temperature). Kidney biopsies (removal of a small piece of tissue for examination under the microscope) will be done at 2 weeks, 1 month and 6 months after surgery and then yearly for 4 years to check for any damage to the kidney. In addition, a local doctor will do routine laboratory tests 2 to 3 times a week for the first 2 to 3 months aft...

Eligibility Criteria

INCLUSION CRITERIA:

Candidates for a kidney transplant performed at the NIH Clinical Center.

Willingness and legal ability to give informed consent.

Availability of donor tissue for testing. This could include splenic or peripheral blood lymphocytes from a cadaveric donor or a willing living donor enrolled on the Clinical Center Living Donor Protocol who consents to periodic phlebotomy for peripheral blood lymphocyte isolation.

EXCLUSION CRITERIA

Immunosuppressive drug therapy at the time of or 2 months prior to enrollment. Specifically, candidates may not be taking prednisone, cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, anti-lymphocyte agents, cyclophosphamide, methotrexate, or other agents whose therapeutic effect is immunosuppressive.

Any active malignancy or any history of a hematogenous malignancy or lymphoma. Patients with primary, cutaneous basal cell or squamous cell cancers may be enrolled providing the lesions are appropriately treated prior to transplant.

Significant coagulopathy or requirement for anticoagulation therapy that would contraindicate protocol allograft biopsies.

Platelet count less than 100,000/mm(3).

Any known immunodeficiency syndrome.

Any history of cardiac insufficiency, major vascular disease, symptomatic coronary artery disease.

Systemic or pulmonary edema.

Inability to be effectively dialyzed.

Any condition that would likely increase the risk of protocol participation or confound the interpretation of the data.

Any history of sensitization to rabbits or extensive exposure to rabbits.

Inability or unwillingness to comply with protocol monitoring and therapy, including, among others, a history of noncompliance, circumstances where compliance with protocol requirements is not feasible due to living conditions, travel restrictions, access to urgent medical services, or access to anti-rejection drugs after the research protocol is completed.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00006178). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.