Pediatric Kidney Transplant Without Calcineurin Inhibitors

NCT00023231 | Completed

• 2 other identifiers: DAIT CN01CN01
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to see the effect of using drugs other than calcineurin inhibitors to improve the rate of kidney transplant failure. Kidney transplantation can help children with end-stage kidney disease. However, it has been difficult to find treatment for donor graft rejection that does not have a lot of side effects. Researchers hope to find treatments (immunosuppressants) with fewer side effects. One approach is to avoid using calcineurin inhibitors and to try a new drug known as sirolimus instead. Another is to use steroids less often. This study will test whether using sirolimus, fewer steroid treatments, MMF, and certain antibodies will improve long-term graft survival in children receiving kidney transplants from living donors.

Conditions

End-Stage Renal Disease

Outcome Measures

Primary Outcomes (2)

• Efficacy of treatment without calcineurin inhibitors, compared to current standard immunosuppressive treatment

  Throughout study

• Adverse effects of treatment without calcineurin inhibitors, compared to current standard immunosuppressive treatment, especially hypertension, serious infections and chronic nephrotoxicity

  Throughout study

Secondary Outcomes (1)

• Immune inhibition detected by sensitive and specific assays (including intragraft and peripheral monitoring) for expression patterns of activation and effector function markers

  Throughout study

Study Arms (1)

1

EXPERIMENTAL

Participants will receive immunosuppression therapy using antibody induction (daclizumab), corticosteroids, mycophenolate mofetil, and sirolimus prior to transplantation. Bactrim and ganciclovir will be taken for infection prophylaxis. If the participant has consistent high levels of fasting cholesterol, treatment with lipitor may be given.

Drug: Daclizumab; Drug: Methylprednisolone/prednisone; Drug: Mycophenolate mofetil; Drug: Sirolimus; Drug: Bactrim; Drug: Ganciclovir; Drug: Lipitor

Interventions

Daclizumab DRUG

1 mg/kg/dose at study entry and Weeks 2, 4, 6, and 8

Also known as: Zenapax

1

Methylprednisolone/prednisone DRUG

Dosage is dependent on weight and varies throughout study. Refer to protocol for more information.

Also known as: Cellcept

1

Mycophenolate mofetil DRUG

Solution or oral tablet taken daily. Dosage depends on body surface area.

1

Sirolimus DRUG

Oral tablet taken once prior to transplant. Dosage dependent on body surface area.

Also known as: Rapamune

1

Bactrim DRUG

Oral tablet taken three times per week. Dosage is dependent on weight.

1

Ganciclovir DRUG

Oral tablet taken daily. Dosage is dependent on weight.

1

Lipitor DRUG

Oral tablet taken daily

1

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients may be eligible for this study if they:
• Are 21 years of age and under.
• Are kidney recipients of living-donor grafts, except when living-donor grafts are identically matched.

You may not qualify if:

• Patients will not be eligible for this study if they:
• Are recipients of identical (HLA matched) living-donor grafts.
• Are recipients of cadaver-donor grafts.
• Have certain abnormal kidney diseases that may return.
• Have failed 2 or more previous kidney transplants.
• Have fat abnormalities that are inherited or present at high levels.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Lauren Schenker

Rockville, Maryland, 20850, United States

Location

Related Publications (4)

• Harmon W, Meyers K, Ingelfinger J, McDonald R, McIntosh M, Ho M, Spaneas L, Palmer JA, Hawk M, Geehan C, Tinckam K, Hancock WW, Sayegh MH. Safety and efficacy of a calcineurin inhibitor avoidance regimen in pediatric renal transplantation. J Am Soc Nephrol. 2006 Jun;17(6):1735-45. doi: 10.1681/ASN.2006010049. Epub 2006 May 10.

  PMID: 16687625 RESULT

• Iacomini J, Sayegh MH. Measuring T cell alloreactivity to predict kidney transplant outcomes: are we there yet? J Am Soc Nephrol. 2006 Feb;17(2):328-30. doi: 10.1681/ASN.2005121264. Epub 2005 Dec 28. No abstract available.

  PMID: 16382014 RESULT

• Schachter AD, Meyers KE, Spaneas LD, Palmer JA, Salmanullah M, Baluarte J, Brayman KL, Harmon WE. Short sirolimus half-life in pediatric renal transplant recipients on a calcineurin inhibitor-free protocol. Pediatr Transplant. 2004 Apr;8(2):171-7. doi: 10.1046/j.1399-3046.2003.00148.x.

  PMID: 15049798 RESULT

• Hoerning A, Koss K, Datta D, Boneschansker L, Jones CN, Wong IY, Irimia D, Calzadilla K, Benitez F, Hoyer PF, Harmon WE, Briscoe DM. Subsets of human CD4(+) regulatory T cells express the peripheral homing receptor CXCR3. Eur J Immunol. 2011 Aug;41(8):2291-302. doi: 10.1002/eji.201041095. Epub 2011 Jun 24.

  PMID: 21538345 RESULT

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Daclizumab; Methylprednisolone; Prednisone; Mycophenolic Acid; Sirolimus; Trimethoprim, Sulfamethoxazole Drug Combination; Ganciclovir; Atorvastatin

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Macrolides; Lactones; Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Amides; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pyrroles; Azoles; Heptanoic Acids

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2001
• First Posted: August 31, 2001
• Study Start: February 1, 2001
• Primary Completion: August 1, 2004
• Study Completion: August 1, 2006
• Last Updated: October 21, 2016

Record last verified: 2016-10

Data Sharing

• IPD Sharing: Will share

Locations

US (1)