Sirolimus and Thymoglobulin to Prevent Kidney Transplant Rejection

NCT00006178 | Completed Phase 2 Results

• 2 other identifiers: 00019600-DK-0196
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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...

Conditions

Kidney Failure

Keywords

Renal Failure; Anti-rejection; Apoptosis; Polyclonal Antibody; Kidney Transplant

Outcome Measures

Primary Outcomes (2)

• Serum Creatinine Concentration

  measures at 6 months after intervention

  6 months after intervention

• Serum Creatinine Concentration

  measures at 12 months after intervention

  12 months after intervention

Secondary Outcomes (2)

• Glomerular Filtration Rate (Flow Rate of Filtered Fluid Through the Kidney)

  6 month after intervention

• Glomerular Filtration Rate (Flow Rate of Filtered Fluid Through the Kidney)

  12 months after intervention

Study Arms (1)

Sirolimus and Thymoglobulin

EXPERIMENTAL

Thymoglobulin (Sangstat), a FDA-approved polyclonal rabbit-IgG antithymocyte preparation, will be given for ten days at the time of transplantation to achieve profound lymphocyte depletion. This will be paired with chronic therapy with Sirolimus (rapamycin, Wyeth-Ayerst), an oral immunosuppressant agent recently approved by the FDA.

Drug: Sirolimus; Drug: Thymoglobulin

Interventions

Sirolimus DRUG

Sirolimus and Thymoglobulin

Thymoglobulin DRUG

Sirolimus and Thymoglobulin

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Matas AJ, Gillingham KJ, Sutherland DE. Half-life and risk factors for kidney transplant outcome--importance of death with function. Transplantation. 1993 Apr;55(4):757-61. doi: 10.1097/00007890-199304000-00014.

  PMID: 8475549 BACKGROUND

• Morris PJ. Renal transplantation: a quarter century of achievement. Semin Nephrol. 1997 May;17(3):188-95.

  PMID: 9165648 BACKGROUND

• Swanson SJ, Hale DA, Mannon RB, Kleiner DE, Cendales LC, Chamberlain CE, Polly SM, Harlan DM, Kirk AD. Kidney transplantation with rabbit antithymocyte globulin induction and sirolimus monotherapy. Lancet. 2002 Nov 23;360(9346):1662-4. doi: 10.1016/S0140-6736(02)11606-0.

  PMID: 12457792 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Renal Insufficiency

Interventions

Sirolimus; thymoglobulin

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

Optimal dose of RATG remains to be determined. Whether other depleting agents are as effective as RATG is unclear.

Results Point of Contact

• Title: Dr. Allan D. Kirk
• Organization: National Institutes of Health

allank@intra.niddk.nih.gov

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2000
• First Posted: August 16, 2000
• Study Start: August 1, 2000
• Primary Completion: December 1, 2007
• Study Completion: December 1, 2007
• Last Updated: September 17, 2019
• Results First Posted: February 11, 2010

Record last verified: 2010-06

Locations

US (1)